Table of Contents
image Rationales for micronutrient supplementation in diabetes
image Contraction and relaxation of aortas from diabetic rats: effects of chronic anti-oxidant and aminoguanidine treatments.
image Antioxidant vitamins in hospitalized elderly patients: Analysed dietary intakes and biochemical status
image Antioxidant depletion, lipid peroxidation, and impairment of calcium transport induced by air-blast overpressure in rat lungs
image The use of antioxidants in healing
image Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids.
image Dietary intake and plasma levels of antioxidant vitamins in health and disease: A hospital-based case-control study
image Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction
image Antioxidant therapy using high dose vitamin C: Reduction of postburn resuscitation fluid volume requirements
image Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise
image Modification of the daily photoreceptor membrane shedding response in vitro by antioxidants
image Tirilazad mesylate protects vitamins C and E in brain ischemia-reperfusion injury
image Biochemical basis of ozone toxicity
image Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats
image An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes
image Antioxidants, fat and skin cancer
image Photoprotective effect of superoxide scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse
image Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation
image Diminished production of malondialdehyde after carotid artery surgery as a result of vitamin administration
image Spermine partially normalizes in vivo antioxidant defense potential in certain brain regions in transiently hypoperfused rat brain
image Positron-labeled antioxidant 6-deoxy-6-(18F)fluoro-L-ascorbic acid: Increased uptake in transient global ischemic rat brain
image Maternal infusion of antioxidants (Trolox and ascorbic acid) protects the fetal heart in rabbit fetal hypoxia
image Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study
image Antioxidant vitamins and disease - Risks of a suboptimal supply
image Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: An epidemiological update with special attention to carotene and vitamin C
image Oxidative protein damage in human diabetic eye: evidnal participation.
image Abnormalities in diabetes or experimental galactosemia. IV. Antioxidant defense system.
image Nutritional antioxidants, red cell membrane fluidity and blood viscosity in type 1 (insulin dependent) diabetes mellitus.
image [Prospective biochemical study of the antioxidant defense capacity in retinopathy of premokemiai vizsgalata retinopathia preamaturorumban.
image [Antioxidants for prophylaxis of eye diseases]
image [Erythrocyte and plasma antioxidant activity in diabetes mellitus type I]
image Oxidative protein damage in human diabetic eye: Evidence of a retinal participation
image Abnormalities of retinal metabolism in diabetes or experimental galactosemia. III. Effects of antioxidants
image Oxidative stress and diabetic vascular complications
image Pharmacological prevention of diabetic microangiopathy
image Erythrocyte and plasma antioxidant activity in type I diabetes mellitus
image Status of antioxidants in patients with diabetes mellitus with and without late complications
image Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.
image Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury.
image Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson's disease.
image [The dose-dependent effects of a combination of different classes of antioxidants exemplified by dibunol and beta-carotene]
image Oxidative damage and defense.
image The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis.
image Reliability of a food frequency questionnaire to assess dietary antioxidant intake.
image Dietary antioxidants and Parkinson disease. The Rotterdam Study.
image Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities.
image Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study.
image [Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)]
image Beta-2-agonists have antioxidant function in vitro. 2. The effect of beta-2-agonists on oxidant-mediated cytotoxicity and on superoxide anion generated by human polymorphonuclear leukocytes.
image Antioxidants in the prevention of atherosclerosis.
image Bronchial reactivity and dietary antioxidants.
image Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol.
image [Alcohol and free radicals: from basic research to clinical prospects]
image Oxidized low-density lipoprotein and atherosclerosis.
image Serum levels of antioxidant vitamins in relation to coronary artery disease: a case control study of Koreans.
image Antioxidants in food and chronic degenerative diseases.
image Randomized trials of dietary antioxidants in cardiovascular disease prevention and treatment.
image Basic research in antioxidant inhibition of steps in atherogenesis.
image Oxidative susceptibility of low-density lipoproteins--influence of regular alcohol use.
image Do hydroxy-carotenoids prevent coronary heart disease? A comparison between Belfast and Toulouse.
image Antioxidants in cardiovascular disease: randomized trials.
image Randomized trial of antioxidants in the primary prevention of Alzheimer disease warranted?
image Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.
image Update on dietary antioxidants and cancer.
image Antioxidants in health and disease
image Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2: antioxidant intervention and conclusions.
image Multicenter ophthalmic and nutritional age-related macular degeneration study--part 1: design, subjects and procedures.
image Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?
image The role of oxidized lipoproteins in atherogenesis.
image [Bronchopulmonary dysplasia]
image Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model.
image [The significance of oxidized low density lipoprotein in atherosclerosis]
image In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation.
image Antioxidants and age-related eye disease. Current and future perspectives.
image [Free radicals in the central nervous system]
image Protection by multiple antioxidants against lipid peroxidation in rat liver homogenate.
image Inhibition of Ca2+-pump ATPase and the Na+/K+-pump ATPase by iron-generated free radicals. Protection by 6,7-dimethyl-2,4-DI-1-pyrrolidinyl-7H-pyrrolo[2,3-d] pyrimidine sulfate (U-89843D), a potent, novel, antioxidant/free radical scavenger.
image Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women
image Oxidative stress and antioxidant therapy in Parkinson's disease
image In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.
image Antioxidant mechanism and protection of nigral neurons against MPP+ toxicity by deprenyl (selegiline)
image Parkinson's disease: a chronic, low-grade antioxidant deficiency?
image Free radicals in brain metabolism and pathology.
image Free radicals and their scavengers in Parkinson's disease.
image Role of dietary lipid and antioxidants in bone metabolism
image [Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]
image COSMETICS -- Marketing
image Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis.
image On the causes of multiple sclerosis
image Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients with breast tumors.
image Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York, United States)
image Extraocular, limb and diaphragm muscle group-specific antioxidant enzyme activity patterns in control and mdx mice.
image Free radicals, lipid peroxides and antioxidants in blood of patients ith myotonic dystrophy.
image Antioxidants and angiogenetic factor associated with age-related macular degeneration (exudative type)
image Studies on the mechanism of early onset macular degeneration in c ynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress
image Association of zinc and antioxidant nutrients with age-related maculopathy.
image Antioxidant enzymes of the human retina: Effect of age on enzyme activity of macula and periphery
image Antioxidant enzymes in RBCs as a biological index of age related macular degeneration
image Antioxidant defenses in metal-induced liver damage
image Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage.
image The role of antioxidants in the prevention of cardiovascular diseases
image Essential antioxidants in cardiovascular diseases--lessons for Europe
image Antioxidant vitamin intake and coronary mortality in a longitudinal population study.
image Can anti-oxidants prevent ischaemic heart disease?
image Antioxidant therapy in the aging process.
image Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects.
image Micronutrient profiles in HIV-1-infected heterosexual adults
image Antioxidant-micronutrients and HIV infection
image Can antioxidants prevent ischemic heart disease?
image Antioxidant therapy in the aging process.
image Acute phase response and plasma carotenoid concentrations in older women: Findings from the nun study.
image Endothelial dysfunction: Clinical implications.
image Use of antioxidant vitamins in the cardiovascular disease. A review of epidemiological study and clinical trials.
image The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes.
image Smoking, plasma antioxidants and essential fatty acids before and after nutratherapy.
image Reduction of plasma peroxide levels by oral antioxidants.
image Systemic oxidative stress in asthma, COPD, and smokers
image Role of oxidants/antioxidants in smoking-induced lung diseases
image Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus
image Spice constituents scavenging free radicals and inhibiting pentosidine formation in a model system.
image Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies.
image Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3
image Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine
image Nutritional antioxidants and the modulation of inflammation: theory and practice.
image Antioxidant vitamins in cataract prevention.
image Free radical tissue damage: protective role of antioxidant nutrients.
image Free radical tissue damage: protective role of antioxidant nutrients.
image [Antioxidative vitamins and cataracts in the elderly]
image Prevention of cataracts by nutritional and metabolic antioxidants.
image Free radicals, exercise, and antioxidant supplementation
image Fibronectin fragment mediated cartilage chondrolysis. I. Suppression by anti-oxidants
image Overview of conditioning related life-threatening toxicities of marrow transplantation
image [Cardioprotection in chemo- and radiotherapy for malignant diseases--an echocardiographic pilot study]
image Place of antioxidants in active photoprotection
image Indicators of free radical activity in patients developing radiation pneumonitis
image The effect of antioxidants on bleomycin treatment in in vitro and in vivo genotoxicity assays
image Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus.
image Free radical tissue damages in the anterior segment of the eye in experimental autoimmune uveitis
image Intervention at diagnosis of type I diabetes using either antioxidants or photopheresis
image Free radical theory of aging: Beneficial effect of antioxidants on the life span of male NZB mice: Role of free radical reactions in the deterioration of the immune system with age and in the pathogenesis of systemic lupus erythematosus
image Reduced superoxide dismutase in lung cells of patients with asthma
image Antioxidant protection against adrenaline-induced arrhythmias in rats with chronic heart hypertrophy.
image The effects of antioxidants on reperfusion dysrhythmias
image [Essential antioxidants in cardiovascular diseases--lessons for Europe]
image Muscle ubiquinone and plasma antioxidants in effort angina
image Effect of antioxidants on postoperative hyperamylasemia in coronary bypass surgery
image Antioxidant depletion during aortic aneurysm repair
image Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting
image Evaluation of antioxidants, protein, and lipid oxidation products in blood from sporadic amiotrophic lateral sclerosis patients.
image Antioxidants in peripheral nerve.
image Free Radicals and Neuroprotection
image Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases.
image Experience over 17 years with antioxidant treatment in Spielmeyer-Sjogren disease.
image Antioxidant of the coronary diet and disease
image Enhanced capacity of n-3 fatty acid-enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins
image The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein
image Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men
image Animal studies on antioxidants
image Abnormal antioxidant vitamin and carotenoid status in chronic renal failure
image Antioxidants in cardiovascular disease: Randomized trials
image Dietary antioxidants and cognitive function in a population-based sample of older persons: The Rotterdam study
image Oxidized low density lipoproteins in atherogenesis: Role of dietary modification
image Antioxydant vitamins and risk of cardiovascular diseases
image The significance of oxidised low-density lipoprotein in atherosclerosis
image Prevention of atherosclerosis with dietary antioxidants: Fact or fiction?
image Randomized, controlled trial of antioxidant vitamins and cardioprotective diet on hyperlipidemia, oxidative stress, and development of experimental atherosclerosis: The diet and antioxidant trial on atherosclerosis (DATA)
image Optimal diet for reducing the risk of arteriosclerosis
image Prevention of atherosclerosis: The potential role of antioxidants
image Advanced glycation endproducts in ageing and Alzheimer's disease
image Molecular basis of Alzheimer's disease.
image New therapeutic approaches to Alzheimer's disease.
image A pilot study of blood antioxidant and free radical marker profiles in patients awaiting coronary artery bypass grafting
image Oxygen free radical-induced histamine release during intestinal ischemia and reperfusion
image Antioxidant drugs block in vitro the neurotoxicity of CSF from atients with amyotrophic lateral sclerosis
image The role of antioxidant agents on experimental ulcerative colitis
image Rutoside as mucosal protective in acetic acid-induced rat colitis
image Inhibitory effect of a traditional Chinese medicine, Juzen-taiho-to, on progressive growth of weakly malignant clone cells derived from murine fibrosarcoma.


Abnormalities of retinal metabolism in diabetes or experimental galactosemia. III. Effects of antioxidants

Diabetes (USA), 1996, 45/9 (1233-1237)

Effects of antioxidants on hyperglycemia-induced alterations of retinal metabolism were evaluated in rats diabetic or experimentally galactosemic for 2 months. Oxidative stress was estimated by measuring lipid peroxides (measured as thiobarbituric acid reactive substances (TBARS)) in retina and plasma. Erythrocyte osmotic fragility, another measure of oxidative stress, also was determined in the same groups of rats. In diabetic rats, TBARS were elevated by 74% in retina and 87% in plasma. In galactose-fed rats, TBARS were significantly elevated in retina (P < 0.05), but were normal in plasma. The administration of supplemental dietary ascorbic acid and alpha-tocopherol acetate for 2 months prevented the elevation of retinal TBARS and the decrease of Na+-K+-ATPase and calcium ATPase activities in retinas of diabetic animals without having any beneficial effect on plasma TBARS. In galactosemic rats, these antioxidants had a partial beneficial effect on the activity of retinal Na+-K+-ATPase, but failed to have any effect on calcium ATPase. The beneficial effects of antioxidants in diabetes and experimental galactosemia were not caused by the amelioration of hyperglycemia or retinal polyol accumulation. Erythrocyte osmotic fragility was increased by more than twofold in diabetes, but was normal in experimental galactesemia, and antioxidants prevented diabetes-induced increases in erythrocyte osmotic fragility. Diabetes-induced increased oxidative stress and subnormal ATPase activities in the retina can be inhibited by dietary supplementation with antioxidants.

Oxidative stress and diabetic vascular complications

Diabetes Care (USA), 1996, 19/3 (257-267)

Long-term vascular complications still represent the main cause of morbidity and mortality in diabetic patients. Although prospective randomized long-term clinical studies comparing the effects of conventional and intensive therapy have demonstrated a clear link between diabetic hyperglycemia and the development of secondary complications of diabetes, they have not defined the mechanism through which excess glucose results in tissue damage. Evidence has accumulated indicating that the generation of reactive oxygen species (oxidative stress) may play an important role in the etiology of diabetic complications. This hypothesis is supported by evidence that many biochemical pathways strictly associated with hyperglycemia (glucose autoxidation, polyol pathway, prostanoid synthesis, protein glycation) can increase the production of free radicals. Furthermore, exposure of endothelial cells to high glucose leads to augmented production of superoxide anion, which may quench nitric oxide, a potent endothelium- derived vasodilator that participates in the general homeostasis of the vasculature. In further support of the consequential injurious role of oxidative stress, many of the adverse effects of high glucose on endothelial functions, such as reduced endothelial-dependent relaxation and delayed cell replication, are reversed by antioxidants. A rational extension of this proposed role for oxidative stress is the suggestion that the different susceptibility of diabetic patients to microvascular and macrovascular complications may be a function of the endogenous antioxidant status.

Pharmacological prevention of diabetic microangiopathy

DIABETE METABOL. (France), 1994, 20/2 BIS (219-228)

The development of drugs in order to block metabolic pathways of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamine E, vitamine C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy.

Erythrocyte and plasma antioxidant activity in type I diabetes mellitus

Presse Medicale (France), 1996, 25/5 (188-192)

Objectives: Some biologic parameters involved in cell defence against oxygen radicals (plasmatic vitamins C and E, erythrocyte glutathione peroxidase, glutathione reductase and superoxide dismutase) were measured in single blood samples from 119 diabetic infants, adolescents and young adults. Methods: Data were studied in relation to residual insulin secretion determined by C peptide, level of metabolic control appreciated by glycosylated haemoglobin, lipid abnormalities and subclinical complications (retinopathy, neuropathy and nephropathy). Results: There was no change in antioxidant parameters with insulin secretion. Patients with poor glycaemic control and high plasma lipids had higher levels of plasma vitamin E. Patients with nephropathy had lower plasma vitamin C levels and those with neuropathy showed lower erythrocyte glutathione peroxidase activity. Plasma vitamin C concentrations and erythrocyte glutathione reductase activities were negatively correlated with the age of the patients and the duration of the disease. Conclusion: Higher transport capacity of vitamin E probably explains the elevated levels of vitamin E observed in patients with high lipid levels and long lasting illness. The lower levels of vitamin C in the presence of nephropathy may be due to an increased renal excretion of this vitamin. The reduction of glutathione peroxidase, glutathione reductase activities and vitamin C levels confirms the existence of an oxidative stress in type 1 diabetes

Status of antioxidants in patients with diabetes mellitus with and without late complications

AKTUEL. ERNAHR.MED. KLIN. PRAX. (Germany), 1994, 19/3 (155-159)

The role of antioxidative vitamins in the therapy of diabetes mellitus is of growing importance. The development of diabetic late complications (cataract, retinopathy, nephropathy and neuropathy and others) is associated with an increased presence of free radicals, and therefore, elevated oxidative stress of the human body. The aim of the present study was the evaluation of the vitamin and selenium status of diabetics. Thirty-eight patients of the age of 35-58 years had been diabetics for 8-27 years and their plasma concentration of haemoglobin was 6.7-7.5%. The diabetics of type I were treated with a functional insulin therapy with dietary restrictions, whereas the type II diabetics received oral antidiabetica (sulfonyl urea, biguanids) and had to comply with a fixed diet. Any supplementation of vitamins was omitted. The nutritional intake was monitored by a weighed record over 7 days. The plasma concentrations of vitamin A, beta-carotone, K and E were determined by reversed-phase-PLC. For the assessment of vitamin C concentrations, a photometric method was used, and selenium concentrations was determined by electrothermal atomic absorption spectrometry. Mean values of plasma concentrations were: vitamin A 36-50 microg/dl, beta-carotene 35-42 microg/dl, vitamin K: 0.5-0.6 ng/ml, vitamin E: 1.1-1.6 mg/dl, selenium: 72-75 microg/l. The values of vitamin C concentration of the diabetics type I without late complications and of type II diabetics were at 0.8 mg/dl and, therefore, at the borderline. Diabetics of type I with late complications showed marginal values of 0.6 plus or minus 0.3 mg/dl. The critical value for the prevention of scorbut has been fixed at 0.4 mg/dl. The results of this confirm the importance and efficiency of vitamins, especially of ascorbic acid. Positive effects of this antioxidative vitamin in respect of the prevention of diabetic side effects and subsequent disease should therefore be expected.

Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.

Darr D; Dunston S; Faust H; Pinnell S

North Carolina Biotechnology Center, Raleigh, N.C., USA.

Acta Derm Venereol (NORWAY) Jul 1996, 76 (4) p264-8,

Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.

Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury.

Gonzalez PK; Zhuang J; Doctrow SR; Malfroy B; Benson PF; Menconi MJ; Fink MP

Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215, Shock (UNITED STATES) 1996, 6 Suppl 1 pS23-6

/Reactive oxygen metabolites (ROMs) are thought to play a key role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Accordingly, the use of ROM scavengers, such as N-acetyl-cysteine or dimethylthiourea, as therapeutic adjuncts to prevent oxidant-mediated damage to the lung have been evaluated extensively in animal models of ARDS. Results with this approach have been quite variable among studies. Another strategy that has been examined in animal models of ARDS is the administration of various enzymes, particularly superoxide dismutase (SOD) or catalase (CAT), in an effort to promote the conversion of ROMs to inactive metabolites. In theory, this strategy should be more effective than the use of ROM scavengers since a single molecule of a catalytically active molecule can neutralize a large number of molecules of a reactive species, whereas most scavengers act in a stoichiometric fashion to neutralize radicals on a mole-for-mole basis. This notion is supported by studies showing that prophylactic treatment with CAT provides impressive protection against acute lung injury induced in experimental animals by the administration of lipopolysaccharide (LPS). Results with SOD have been more variable. Recently, we have utilized a porcine model of LPS-induced ARDS to investigate the therapeutic potential of EUK-8, a novel, synthetic, low molecular salen-manganese complex that exhibits both SOD-like and CAT-like activities in vitro. Using both pre- and post-treatment designs, we have documented that treatment with EUK-8 significantly attenuates many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance, and pulmonary edema. These findings support the view that salen-manganese complexes warrant further nt or prevention of sepsis-related ARDS in humans. (54 Refs.)

Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson's disease.

Offen D; Ziv I; Sternin H; Melamed E; Hochman A

Department of Neurology, Beilinson Medical Center, Petah-Tiqva, Israel.

Exp Neurol (UNITED STATES) Sep 1996, 141 (1) p32-9

We have recently shown that dopamine (DA) can trigger apoptosis, an active program of cellular self-destruction, in various neuronal cultures and proposed that inappropriate activation of apoptosis by DA and or its oxidation products may initiate nigral cell loss in Parkinson's disease (PD). Since DA toxicity may be mediated via generation of oxygen-free radical species, we examined whether DA-induced cell death in PC12 cells may be inhibited by antioxidants. We have found that the thiol containing compounds, reduced glutathione (GSH), N-acetyl-cysteine (NAC), and dithiothreitol (DTT) were markedly protective, while vitamins C and E had lesser or no effect. The thiol antioxidants and vitamin C but not vitamin E, prevented dopamine autooxidation and production of dopamine-melanin. Their protective effect has also manifested by inhibiting DA-induced apoptosis; DNA fragmentation was prevented as was shown histochemically by the in situ end-labeled DNA technique (TUNEL). Intracellular GSH and other thiols constitute an important natural defense against oxidative stress. We have found that depletion of cellular GSH by the addition of phoron, a substrate of glutathione transferase, and buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl transpeptidase, significantly enhanced DA toxicity. Cotreatment with NAC rescued the cells from the toxic effect of BSO+DA, and phoron+ DA, while addition of GSH provided only partial protection from BSO+DA toxicity. Our data indicate that the thiol family antioxidants, but not vitamins C and E, are highly effective in rescuing cells from DA-induced apoptosis. Further study of the mechanisms underlying the unique protective capacity of thiol antioxidants may lead to the development of new neuroprotective therapeutic strategies for PD.

[The dose-dependent effects of a combination of different classes of antioxidants exemplified by dibunol and beta-carotene]

Minenkova EA; Barsel' VA; Pichugin VV; Gagarina AB; Evteeva NM; Paramonova MIu; Maikova GG

Izv Akad Nauk Ser Biol (RUSSIA) Mar-Apr 1996, (2) p147-52

In order to enhance antioxidant protection of the organism in various pathological states, effective combinations of antioxidants have been developed that interact with various types of free radicals. On two experimental models,--acute alcohol intoxication and calcium chloride arrhythmia of rats, the prophylactic activity of antioxidant combinations was established for certain doses, rather then for monotherapy. The possibility of obtaining high protective effects at relatively low concentrations of the components in the complex preparation was shown. Am increase of antioxidant concentration in the preparation could decrease its efficiency. The highest efficiency in the complex preparations, as compared with in each component taken separately, was observed in the case of calcium chloride arrhythmia when dibunol and beta-carotene were combined at concentrations of 10 mg/kg and in the case of acute alcohol intoxication (1 and 0.25 mg/kg, respectively). Enhanced efficiency of combined antioxidant therapy opens up the way to the production of new active complex preparations with minimum toxic side toxic effects and complications.

Oxidative damage and defense.

Jacob RA; Burri BJ

USDA, Agricultural Research Service, Western Human Nutrition Research Center, San Francisco, CA 94129, USA.

Am J Clin Nutr (UNITED STATES) Jun 1996, 63 (6) p985S-990S

Increased production of reactive oxygen species is a feature of most, if not all, human disease, including cardiovascular disease and cancer. Dietary antioxidants may g against human diseases associated with free radical damage to cellular DNA, lipids, and proteins. Ascorbic acid is an effective water-soluble antioxidant, and epidemiologic studies suggest that increased ascorbate nutriture is associated with reduced risk of some degenerative diseases, especially cancer and eye cataracts. Population studies have also shown that high vitamin E intakes are associated with decreased risk of coronary heart disease, possibly as a result of inhibition of atherogenic forms of oxidized low-density lipoprotein. Recent data suggest that beta-carotene provides protection against lipid peroxidation in humans, as well as provitamin A activity. Yet, present data are not sufficient to quantitate micronutrient requirements needed to protect against oxidative damage. The antioxidant roles of many food constituents, such as polyphenols, have not been clarified. Most antioxidants can act as prooxidants under certain conditions, and more research is needed to determine the occurrence and importance of this in vivo. The few controlled intervention trials carried out so far have shown mixed results as to the potential of antioxidant supplements for reducing the incidence of chronic diseases. Definitive recommendations on antioxidant intakes for disease prevention must await evidence from controlled studies and intervention trials, some currently in progress. Overall, the present data suggest that protection against oxidative damage and related disease is best served by the variety of antioxidant substances found in fruit and vegetables. (43 Refs.)

The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis.

Kwiterovich PO Jr

Johns Hopkins University School of Medicine, Department of Pediatrics and Medicine, Baltimore, MD 21287-3654, USA.

J Am Diet Assoc (UNITED STATES) Jul 1997, 97 (7 Suppl) pS31-41

A number of primary and secondary prevention trials, including angiographic studies, have indicated that a decrease in dietary saturated fat and cholesterol produces a decrease in the blood levels of cholesterol and low-density lipoprotein (LDL) cholesterol, leading to a decrease in coronary artery disease (CAD). Increasing evidence indicates that the oxidation of LDL in human beings is atherogenic. Of the three major antioxidants, vitamin E, beta carotene, and vitamin C, the evidence is strongest that vitamin E (at a minimum dose of 100 IU/day) has a strong and independent inverse association with CAD. Selenium and flavonoids also have antioxidant properties, but their association with CAD in human beings is equivocal. Two prooxidants, homocysteine and iron, have been found to be associated with CAD. Blood homocysteine levels can be lowered significantly by an increase in dietary folic acid. Clinical trials are needed to assess expeditiously the effect of antioxidants, particularly vitamin E, and of folic acid on CAD and atherosclerosis. The substitution of monounsaturated fat for saturated fat lowers LDL and makes it less susceptible to oxidation without decreasing high-density lipoprotein (HDL) cholesterol. Studies in transgenic mice indicate that apolipoprotein A-I, the major protein of HDL, may inhibit the oxidation of LDL. Dietary trans fatty acids at the level consumed by many Americans can increase LDL cholesterol and may decrease HDL cholesterol. Individuals who have CAD or have family members who have premature CAD have delayed clearance of dietary fat, as judged by studies of postprandial triglyceride metabolism. The importance of decreasing dietary saturated fat and cholesterol is well established, but a number of other factors appear to influence the risk of CAD significantly and provide important areas for future investigation to improve prevention and treatment through better nutrition. (75 Refs.)

Reliability of a food frequency questionnaire to assess dietary antioxidant intake.

McCarty CA; De Paola C; Livingston PM; Taylor HR

Dept. Ophthalmology, Royal Victorian Eye & Ear Hospital, East Melbourne, Australia.

Ophthalmic Epidemiol (NETHERLANDS) Mar 1997, 4 (1) p33-9

OBJECTIVE: Epidemiologic evidence of a role for antioxidants in the prevention of chronic disease has been inconclusive, in part due to the difficulty of measuring past diets of free-living populations. The purpose of the current study was to examine the reliability of a 19-item, self-administered, semiquantitative, food frequency questionnaire to assess intake of the major dietary antioxidants. METHODS: Reliability was established by administering the food frequency questionnaire a second time by telephone. The subjects comprised 151 participants in the Melbourne Visual Impairment Project, a study of the distribution and determinants of eye disease in Melbourne residents aged 40 and over. RESULTS: Spearman correlation coefficients ranged from 0.39 for spinach to 0.76 for yoghurt, and all were highly significant (all p = 0.001). The reliability of the instrument was not influenced by gender, English speaking ability, or the number of days between the first and second administration of the questionnaire. uency questionnaire to be highly reliable. It should be usef ul for anyone involved in the study of the relationship of dietary antioxidant intake to health outcomes in large populations where limitations of time and money prohibit the collection of more detailed dietary intake information.

Dietary antioxidants and Parkinson disease. The Rotterdam Study.

de Rijk MC; Breteler MM; den Breeijen JH; Launer LJ; Grobbee DE; van der Meche FG; Hofman A

Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherland.

Arch Neurol (UNITED STATES) Jun 1997, 54 (6) p762-5

OBJECTIVE: To investigate whether high dietary intake of antioxidants decreases the risk of Parkinson disease (PD). SETTING: The community-based Rotterdam Study, the Netherlands. DESIGN: The cross-sectional study formed part of a large community-based study in which all participants were individually screened for parkinsonism and were administered a semiquantitative food frequency questionnaire. The study population consisted of 5342 independently living individuals without dementia between 55 and 95 years of age, including 31 participants with PD (Hoehn-Yahr stages 1-3). RESULTS: The odds ratio for PD was 0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4-1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids intake, all adjusted for age, sex, smoking habits, and energy intake. The association with vitamin E intake was dose dependent (P for trend = .03). To assess whether the association was different in participants with more advanced disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This did not fundamentally alter the results. CONCLUSION: Our data suggest that a high intake of dietary vitamin E may protect against the occurrence of PD.

Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities.

Iribarren C; Folsom AR; Jacobs DR Jr; Gross MD; Belcher JD; Eckfeldt JH

Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454-1015, USA.

Arterioscler Thromb Vasc Biol (UNITED STATES) Jun 1997, 17 (6) p1171-7

Oxidative modification of LDL is believed to be a crucial step in atherosclerosis. Thus, antioxidant vitamins may have a role in the prevention of coronary disease. We examined the cross-sectional association of serum vitamin levels, the susceptibility of LDL to hemin-induced oxidation (lag phase to conjugated diene formation), and the malondialdehyde-LDL (MDA-LDL) to native LDL radioacomatic early atherosclerosis. The participants in this observational study were 231 asymptomatic age-, sex-, race-, and field center-matched case-control pairs selected from the Atherosclerosis Risk in Communities (ARIC) study cohort on the basis of B-mode carotid artery ultrasonograms obtained from 1986 through 1989. Cases exceeded the 90th percentile of IMT, and control subjects were below the 75th percentile of IMT for all arterial segments. Biochemical analyses were performed on fasting frozen (-70 degrees C) serum specimens collected from 1990 through 1992. In conditional logistic regression adjusting for age, blood storage time, total cholesterol, and log-triglyceride concentrations, serum beta-cryptoxanthin and lutein plus zeaxanthin levels were inversely related to the extent of atherosclerosis (odds ratio [OR] per 1-SD increase: 0.75, 95% confidence interval [CI]: 0.59-0.94; and OR per 1-SD increase: 0.76, 95% CI: 0.59-0.95, respectively). Increases in alpha-carotene and lycopene were associated with nonsignificantly lower odds of being a case, whereas beta-carotene, retinol, and alpha-tocopherol were unrelated to IMT. Although not reaching statistical significance, the lag phase and autoantibodies against MDA-LDL were positively associated with asymptomatic atherosclerosis. After adjustment for potential confounders, only the inverse association of lutein plus zeaxanthin with asymptomatic atherosclerosis was maintained. This study supports a modest inverse association between circulating levels of some carotenoids, particularly lutein plus zeaxanthin, and carotid IMT. These findings suggest that these carotenoid compounds (regarded as biomarkers of fruit and vegetable intake) may be important in early stages of atherosclerosis.

Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study.

Hertog MG; Sweetnam PM; Fehily AM; Elwood PC; Kromhout D

Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and the Environment, Bilthoven, Netherlands.

Am J Clin Nutr (UNITED STATES) May 1997, 65 (5) p1489-94

Antioxidant flavonols and their major food source, black tea, have been associated with a lower risk of ischemic heart disease (IHD) and stroke in Dutch men. We investigated whether flavonol intake predicted a lower rate of IHD in 1900 Welsh men aged 45-59 y, who were followed up for 14 y. Flavonol intake, mainly from tea to which milk is customarily added, was not related to IHD incidence [relative risk (RR), highest compared with lowest quartile: 1.0; 95% CI: 0.6, 1.6; P for trend = 0.996; n = 186] but was weakly positively related to IHD mortality (RR: 1.6; 95% CI: 0.9, 2.9; P = 0.119; n = 131) and cancer mortality (RR: 1.3; 95% CI: 0.7, 2.3; P = 0.150; n = 104) and strongly related to total mortality (RR: 1.4; 95% CI: 1.0, 2.0; P = 0.014; n = 334). Men with the highest consumption of tea (> 1.2 L, or > 8 cups/d) had an RR of 2.4 (95% CI: 1.5, 3.9) of dying in the follow-up period compared with men consuming < 300 mL/d (< 2 cups/d). We conclude that intake of antioxidant flavonols is not inversely associated with IHD risk in the United Kingdom. Possibly, flavonols from tea to which milk is added are not absorbed; experimental evidence suggests that adding milk to tea abolishes the plasma antioxidant-raising capacity of tea. The apparent association between tea consumption and increased mortality in this population merits further investigation.

[Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)]

Schmidt R; Reinhart B; Schumacher M; Hayn M; Schmidt H; Fazekas F; Niederkorn K; Horner S; Lechner H; Offenbacher H; Eber B; Weinrauch V; Auer-Grumbach P; Kleinert G; Roob G; Kostner GM; Esterbauer H

Universitatskliniken fur Neurologie, Universitat Graz.

Wien Med Wochenschr (AUSTRIA) 1997, 147 (2) p36-40

The Austrian Stroke Prevention Study recruited 1960 randomly selected subjects aged 50 to 75 years during a 3-year period of enrollment. The response rate of the study was 32.4%. A telephone interview with 200 randomly selected non-responders yielded no differences to responders regarding the frequency of major vascular risk factors known to the subjects. Besides demographics, the study assessed arterial hypertension, diabetes mellitus, cardiac disease, smoking, a complete lipid status including the apolipoprotein-E genotype, serum fibrinogen and anticardiolipin antibodies as well as various natural antioxidants such as vitamins A, C, E and beta-carotene. Arterial hypertension, diabetes mellitus, cardiac disease and hypercholesterolemia > 200 mg/dl were strikingly common and occurred in 38%, 7.6%, 32% and 76%, respectively. Suboptimal plasma concentrations of vitamin A, E, and beta-carotene were noted in 77.2%, 56.1% and in 53.2% of study participants. The rate of treatment of major risk factond 70% for arterial hypertension and diabetes me llitus, but only 37.1% and 6.3% for cardiac disease and hypercholesterolemia > 250 mg/dl. Diet was commonly used to treat diabetes but was almost neglected in the treatment of other vascular risk factors. These data provide an orientation on the prevalence of risk factors and the use of primary preventive measures for stroke treatment in our community.

Beta-2-agonists have antioxidant function in vitro. 2. The effect of beta-2-agonists on oxidant-mediated cytotoxicity and on superoxide anion generated by human polymorphonuclear leukocytes.

Gillissen A; Wickenburg D; van Zwoll D; Schultze-Werninghaus G

Department of Internal Medicine, University Hospital Bergmannsheil, Bochum, Germany.

Respiration (SWITZERLAND) 1997, 64 (1) p23-8

Therapeutic agents which may be able to enhance the antioxidant screen of the epithelial surface of the lung have the potential to influence the progression of lung inflammation. This study evaluates the efficacy of a variety of antiasthma drugs to reduce oxidant-mediated cytotoxicity and to inhibit superoxide anion generated by human polymorphonuclear leukocytes. We quantified in vitro the prevention of H2O2-mediated cytotoxicity (lactate dehydrogenase release assay) using the antiasthma drugs as follows: ipratropium bromide, salbutamol (salbutamol base), fenoterol (fenoterol hydrobromide), terbutaline terbutaline sulfate), isoproterenol, prednisolone (prednisolone hydrogensuccinate), beclomethasone (17,21-beclomethasone dipropionate) and reduced glutathione. Furthermore, fenoterol and isoproterenol were evaluated ex vivo to reduce superoxide anion (O2-) generated by freshly isolated polymorphonuclear cells (PMN) from smokers with chronic obstructive lung disease (n = 10). Using a concentration of 10(-4) M, reduction of cytotoxicity was quite different among beta(2)-agonists: fenoterol (97.8%) > isoproterenol (67.6% > salbutamol (41.8%) > terbutaline (30.5%) > ipratropium bromide (18.1%). Corticosteroids and theophylline had no antioxidant effect. The cellular O2- production of freshly isolated PMN was significantly (p < 0.05, comparisons 0 vs. > or = 10(-7) M) reduced with fenoterol and isoproterenol at concentrations > or = 10(-7) M. Propranolol had no inhibitory effect on antioxidant properties of beta(2)-agonists. We hypothesize that the antioxidant function of beta(2)-agonists is related to the number and formation of se results demonstrate that beta(2)-agonists have in part a good intrinsic scavenger function on reactive oxygen species when used in micromolar concentrations. However, to achieve this effect supratherapeutic concentrations were necessary. Thus, the conceivable benefit of beta(2)-agonists in the treatment of high oxidant burden in vivo seems doubtful.

Antioxidants in the prevention of atherosclerosis.

Olsson AG; Yuan XM

Department of Internal Medicine, University Hospital, Linkoping, Sweden.

Curr Opin Lipidol (UNITED STATES) Dec 1996, 7 (6) p374-80

Four antioxidant treatment modalities against atherosclerosis and coronary heart disease are scrutinized: probucol, beta-carotene, alpha-tocopherol and anti-iron treatment. A pattern seems to have emerged in which some treatments look promising, but others are disappointing. Most published studies of antioxidation in atherosclerosis have been ad-hoc in that the primary endpoint of the study has not been a diagnosis related to atherosclerosis; this may be misleading. The most promising antioxidant seems to be alpha-tocopherol, supported by the results of the Cambridge Heart Antecreasing high density lipoprotein concentration and is therefore unlikely to influence atheroma in people. beta-Carotene has been repeatedly shown to be ineffective against coronary heart disease. Anti-iron treatment has not yet been tested in animal models or in man. More has to be learned of the role of antioxidation in atherosclerosis before the effectiveness of this treatment modality can be established. (45 Refs.)

Bronchial reactivity and dietary antioxidants.

Soutar A; Seaton A; Brown K

Department of Environmental and Occupational Medicine, University Medical School, Foresterhill, Aberdeen, UK.

Thorax (ENGLAND) Feb 1997, 52 (2) p166-70

BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.

Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol.

Liebler DC; Stratton SP; Kaysen KL

College of Pharmacy, University of Arizona, Tucson, Arizona, 85721-0207, USA.

Arch Biochem Biophys (UNITED STATES) Feb 15 1997, 338 (2) p244-50

beta-Carotene and other carotenoids are widely regarded as biological antioxidants. However, recent clinical trials indicate that beta-carotene supplements are not effective in disease prevention and raise questions about the biological significance of carotenoid antioxidant actions. To further explore this issue, we have reevaluated the antioxidant actions of beta-carotene in liposomal and biological membrane systems. In dilinoleoylphosphatidylcholine liposomes in which 0.35 mol % beta-carotene was incorporated into the bilayer during liposome preparation, the carotenoid inhibited lipid peroxidation initiated by 10 mm azobis[amidinopropane HCl] (AAPH). In carotenoid-free liposome suspensions to which the same amount of beta-carotene was added, no antioxidant effect was observed. Supplementation of rat liver microsomes with beta-carotene in vitro yielded microsomes containing 1.7 nmol beta-carotene mg-1 and 0.16 nmol alpha-tocopherol mg-1 microsomal protein. In beta-carotene supplemented microsomes incubated with 10 mm AAPH under an air atmosphere, lipid peroxidation did not occur until alpha-tocopherol was depleted by approximately 60%. beta-Carotene exerted no apparent antioxidant effect and was not significantly depleted in the incubations. Similar results were obtained when the incubation was done at 3.8 torr O2. In liver microsomes from Mongolian gerbils fed beta-carotene-supplemented diets, beta-carotene levels were 16-37% of alpha-tocopherol levels. The kinetics of AAPH-induced lipid peroxidation were no different in beta-carotene-supplemented microsomes than in microsomes from unsupplemented animals, although the kinetics of beta-carotene and alpha-tocopherol depletion were similar. The results indicate that beta-carotene is ineffective as an antioxidant when added to preformed lipid bilayer membranes and that alpha-tocopherol is a much more effective membrane antioxidant than beta-carotene, regardless of the method of carotenoid-membrane incorporation. These results support a reevaluation of the proposed antioxidant role for beta-carotene in biological membranes.

[Alcohol and free radicals: from basic research to clinical prospects]

Nordmann R; Rouach H

Biomecicale des Saints-Peres, PARIS.

Ann Gastroenterol Hepatol (Paris) (FRANCE) May-Jun 1996, 32 (3) p128-33; discussion 133-4

Subfile: liver of rats following various conditions of ethanol administration. The ethanol-inducible cytochrome P450 2E1 plays a key role in its generation, favoured itself by an increase in the "redox-active" fraction of intracellular non-heme iron. Administration of ethanol elicits the generation of the 1-hydroxyethyl radical, which has been identified in vivo. Its reactivity contributes to alcohol-induced immunological disturbances. Liver inflammatory and fibrotic disorders can be reproduced in rats by long-term ethanol administration associated with a high fat diet. The severity of these disorders is correlated to the intensity of the oxidative stress. Some conditions of ethanol administration to rats also elicit an oxidative stress in the myocardium and central nervous system. Through its inhibitory effect on glutamine synthetase activity and resulting excitotoxicity it may contribute to neuronal death and possibly to dependence on alcohol. Disorders related to an oxidative stress were also reported in the serum and erythrocytes as well as in liver biopsies from alcoholic individuals. Their detection may be useful to follow the evolution of alcoholic liver diseases. Supplementation with antioxidants such as vitamin E may be considered in the prevention of severe cellular disorders in individuals consuming large amounts of alcoholic beverages. An increase in free radical production is likely playing a role in the induction of severe cellular damage linked to repeated withdrawals occurring as a result of heavy and sporadic ethanol intake. (41 Refs.)

Oxidized low-density lipoprotein and atherosclerosis.

Devaraj S; Jialal I

Center for Human Nutrition and Department of Internal Medicine. University of Texas Southwestern Medical Center, Dallas 75235-9052, USA.

Int J Clin Lab Res (GERMANY) 1996, 26 (3) p178-84

Atherosclerosis is the leading cause of morbidity and mortality in western society. The most important risk factiabetes and a family history of premature atherosclerosis. Several studies indicate that an increased plasma low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Many data support a proatherogenic role for oxidized LDL, and its in vivo existence. The oxidative susceptibility of LDL is increased with established cardiovascular risk factors, such as diabetes, smoking and dyslipidemia. Supplementation with antioxidants such as ascorbate and alpha to copherol can decrease LDL oxidation as well as cardiovascular mortality and thus shows promise in the prevention of atherosclerosis (86 Refs.)

Serum levels of antioxidant vitamins in relation to coronary artery disease: a case control study of Koreans.

Kim SY; Lee-Kim YC; Kim MK; Suh JY; Chung EJ; Cho SY; Cho BK; Suh I

Department of Food and Nutrition, Yonsei University, Seoul, Korea.

Biomed Environ Sci (UNITED STATES) Sep 1996, 9 (2-3) p229-35

With the changes in trends of disease pattern from infectious to chronic degenerative disease, cardiovascular disease has been considered as the major cause of death in Korea. Numerous studies have been done on the antioxidant effects of some vitamins in the prevention of chronic illness, but not many in relation to the cardiovascular disease. Therefore, the relation between antioxidant vitamins, mainly alpha-tocopherol (alpha-T) and beta-carotene (beta-C), and coronary artery disease (CAD) such as angina pectoris and myocardial infarction has been investigated in this study. The blood samples were obtained from the CAD patients who were angiographically diagnosed within a month (100 case group). Patients who had an experience of PTCA or CABG were excluded from the study. Control subjects were healthy adults who had normal EKG values, no chest pain and no past history of cardiac disease (100 control group). All subjects were free for serum lipid lowering drugs. Serum alpha-T and beta-C were analysed using HPLC. In addition to antioxidant vitamins, serum lipids (total cholesterol, HDL, TG) were also measured. Each case and control was matched in terms of age and sex. And all the CAD risk factors such as blood pressure, smoking, alcohol, serum lipid profile and BMI were adjusted to determine pure effect(s) of alpha-T and beta-C on the CAD. The concentrations of both alpha-T and beta-C were significantly lower in the CAD group than those in control group (P < 0.05); in CAD group, mean values of alpha-T and beta-C were 11.9 +/- 7.2 (micrograms/ml), 35.8 +/- 3.1 (micrograms/dl) respectively. As for the levels of beta-C, it shows inverse relation with age, but not for the alpha-T levels. Serum levels of both vitamins did not show any significant differences in terms of sex, but men have a tendency o higher levels of beta-C, but lower levels of alpha-T.

Antioxidants in food and chronic degenerative diseases.

Candlish JK; Das NP

Biochemistry Department, National University of Singapore, Singapore.

Biomed Environ Sci (UNITED STATES) Sep 1996, 9 (2-3) p117-23

Both preventive and chain breaking antioxidants have a role in the limitation of free radical damage. Some of these may be regarded as "classical", like vitamins E and C but others are more recently discovered, such as the flavonoids, widespread in plant tissues, and the muscle constituents anserine and carnosine. The major conditions in which the role of antioxidants is under intense investigation include coronary artery disease, cancer and diabetes. There are theoretical underpinnings for the efficacy of antioxidants in each of these, with the protection of low density lipoprotein (in respect of the first) being exceptionally persuasive. Much attention is now being focussed on the flavonoids, which are surprisingly pleiotropic in their effects. For one of them, quercetin, over a dozen seemingly independent biological effects can be listed, including the inhibition of low density lipoprotein oxidation. Flavonoids also inhibit peroxidation in foodstuffs, as opposed to tissues. Tersy over antioxidant supplementation policies, some authorities recommending a massive programme of supplementation for all ages and classes, others stressing the value of the traditional mixed diet. This matter is unlikely to be resolved soon, but in the meantime sensible supplementation policies should be continued for those most vulnerable, that is, babies and the aged.

Randomized trials of dietary antioxidants in cardiovascular disease prevention and treatment.

Gaziano JM

Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204, USA.

J Cardiovasc Risk (ENGLAND) Aug 1996, 3 (4) p368-71

The hypothesis that antioxidant vitamins might reduce cardiovascular disease risk is based on a large body of basic and human epidemiologic research. Basic research provides a plausible mechanism by which antioxidants might reduce the risk of atherosclerosis. A large number of descriptive, case-control and cohort studies provide data suggesting that consumption of antioxidant vitamins is associated with reduced risks of cardiovascular disease. These data raise the question of a role of antioxidants, such as vitamins C and E, and beta-carotene, in the primary prevention of cardiovascular disease, but do not provide a definitive answer. Randomized trial data will be essential in establishing whether or not there is a causal effect of antioxidants in reducing the risk of cardiovascular disease. For many hypotheses randomized trials are neither necessary nor desirable; however, when searching for small to moderate effects, large-scale randomized trials of adequate dose and duration, in which investigators allocate subjects at random to either active treatment or placebo will provide valuable information about whether there is a causal relationship, and provide reliable estimates of effect size. Results from several large-scale randomized trials of antioxidants are summarized in this paper. At present, there is not sufficient data available to define clearly the role of antioxidants in primary or secondary prevention of cardiovascular disease. Additional trial data should be forthcoming in the near future which will aid in individual clinical decision-making and in the establishment of guidelines for the general public. (19 Refs.)

Basic research in antioxidant inhibition of steps in atherogenesis.

Gokce N; Frei B

Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts 02118, USA.

J Cardiovasc Risk (ENGLAND) Aug 1996, 3 (4) p352-7

Oxidised low-density lipoprotein (LDL) contributes to atherogenesis by a number of mechanisms, and antioxidants may act as anti-atherogens. LDL oxidation is inhibited by LDL-associated antioxidants, particularly alpha-tocopherol (vitamin E), and water-soluble antioxidants present in LDL's biologic milieu, especially ascorbate (vitamin C). In addition to protecting LDL against oxidation, antioxidants may act at the level of the vascular cell by limiting cellular production of reactive oxygen species, and, thus, cell-mediated LDL oxidation. Cellular antioxidants can also protect against vascular cell dysfunction that would otherwise promote atherogenesis, such as increased adhesion molecule expression and monocyte recruitment, impaired production or release of nitric oxide, or both, and the proliferation of smooth muscle cells. Some of these processes are regulated by nuclear factor-kappa B or related transcription factors, which are redox-sensitive and inhibited by antioxidants. Furthermore, cellular antioxidants can limit cytotoxic effects of oxidised LDL and other oxidant insults, inhibiting vascular cell necrosis and lesion progression. Finally, some antioxidants, in particular alpha-tocopherol, may affect atherogenesis by inhibiting platelet function and mural thrombosis, although this effect appears to be explained by the inhibition of protein kinase C independent of alpha-tocopherol's antioxidant activity. (65 Refs.)

Oxidative susceptibility of low-density lipoproteins--influence of regular alcohol use.

Croft KD; Puddey IB; Rakic V; Abu-Amsha R; Dimmitt SB; Beilin LJ

Department of Medicine, Royal Perth Hospital, University of Western Australia.

Alcohol Clin Exp Res (UNITED STATES) Sep 1996, 20 (6) p980-4

In population studies, a low-to-moderate intake of alcohol has been consistently linked to a lower risk of coronary artery disease. The recent suggestion that alcoholic beverages may be conferring this decrease in risk because they contain antioxidant phenolic compounds that reduce the oxidizability of low-density lipoprotein (LDL) has to be reconciled with the possible counteracting influence of a pro-oxidant effect of alcohol. In a controlled crossover study, we have now measured the oxidizability of LDL in 27 regular beer drinkers during consecutive 4-week periods, wherein they consumed a high versus low alcohol beer (4.9 vs. 0.9% alcohol v/v, respectively), with the two beers being similar in phenolic content. This resulted in a decrease in alcohol consumption by approximately 80% (408 +/- 25 ml/week vs. 75 +/- 11 ml/week). During the low alcohol period, there was no change in LDL vitamin E or its cholesterol or protein content. Analysis of LDL oxidation kinetics revealed an increase in oxidizability during the high alcohol phase. This was despite a decrease in arachidonic acid content of LDL and a corresponding increase in palmitic acid during high alcohol intake--a change in fatty acid composition that has the potential to favor a decrease in oxidizability. Our results suggest that alcohol ingestion increases LDL oxidation, despite reducing the polyunsaturated fatty acid composition. The overall effect of alcoholic beverages on LDL oxidation may be a balance between the pro-oxidant and antioxidant activity of its various constituents. The predominant pro-oxidant effect demonstrated in these beer drinkers, although not relevant to any potential decrease in coronary artery disease, may be important in the pathogenesis of alcohol-relat

Do hydroxy-carotenoids prevent coronary heart disease? A comparison between Belfast and Toulouse.

Howard AN; Williams NR; Palmer CR; Cambou JP; Evans AE; Foote JW; Marques-Vidal P; McCrum EE; Ruidavets JB; Nigdikar SV; Rajput-Williams J; Thurnham DI

Department of Pathology, Papworth Hospital NHS Trust, Cambridge, UK.

Int J Vitam Nutr Res (SWITZERLAND) 1996, 66 (2) p113-8

High intakes of antioxidants in fruit, vegetables and wine are thought to protect against coronary heart disease (CHD). Because people in Toulouse have a much lower incidence of CHD compared with Belfast, the plasma concentrations of antioxidant vitamins and carotenoids in the two populations have been compared. The major difference was in some of the plasma carotenoids. Hydroxy-carotenoids were twice as high in Toulouse in both sexes, notably lutein which occurs principally in dark green vegetables and beta-cryptoxanthin which occurs chiefly in citrus fruits. In addition, alpha-carotene was 50% higher in Toulouse, gamma-tocopherol was 50% higher in Belfast. Other plasma vitamins and carotenoids were not significantly different. If antioxidants play a role in preventing CHD, then the hydroxy-carotenoids are major candidates for further investigation.

Antioxidants in cardiovascular disease: randomized trials.

Gaziano JM

Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204, USA.

Nutrition (UNITED STATES) Sep 1996, 12 (9) p583-8

The hypothesis that antioxidant vitamins might reduce cardiovascular disease risk is based on a large body of both basic and human epidemiologic research. One of the most consistent findings in dietary research is that those who consume higher amounts of fruits and vegetables have lower rates of heart disease and stroke as well as cancer. Recent attention has focused on the antioxidant content of fruits and vegetables as a possible explanation for the apparent protective effects. Basic research provides a plausible mechanism by which antioxidants might reduce the risk of atherosclerosis. A large number of descriptive, case-control and cohort studies provide data suggesting that consumption of antioxidant vitamins is associated with reduced risks of cardiovascular disease. These data raise the question of a possible role of antioxidants, such as vitamins C and E, and beta carotene, in the primary prevention of cardiovascular disease but do not provide a definitive answer. Results from several large-scale randomized trials of antioxidant supplements are now available; however, results are not entirely consistent. The results of the major trials do not prove or disprove the value of antioxidant vitamins, nor do they incriminate them as harmful. They do, however, raise the possibility that some of the benefits from observational epidemiology may have been overestimated and that there may be some adverse effects. At this point randomized trial data are not yet sufficient to fully assess the risk-to-benefit ratios for antioxidant supplements. More reliable data should be forthcoming in the near future which will better define the role of antioxidants in the primary and secondary prevention of atherosclerotic disease as well as cancer. (59 Refs.)

Randomized trial of antioxidants in the primary prevention of Alzheimer disease warranted?

Evans DA; Morris MC

Rush Alzheimer's Disease Center, Rush University, Chicago, Illinois 60612, USA.

Alzheimer Dis Assoc Disord (UNITED STATES) Fall 1996, 10 Suppl 1 p45-9

Alzheimer disease is a common condition that severely affects both persons with the illness and their families. Prevention of Alzheimer disease is an urgent priority, but study of potentially modifiable risk factors for the illness is at an early stage. Laboratory studies suggest that oxidative mechanisms may be involved in the pathogenesis of Alzheimer disease and raise the possibility that antioxidant nutrients could be used in disease prevention. Observational studies suggest that antioxidant nutrients may have protective effects against a number of other common chronic diseases, including cardiovascular disease and cancer. Because the protective effects, if any, of antioxidant nutrients are likely to be small to moderate in magnitude, large-scale randomized trials of primary prevention will likely be necessary to resolve this issue, and a major question is how quickly to progress to expensive and time consuming trials needed to provide more definitive evidence. This is a difficult question, but the severity of the disease, the current absence of preventive strategies and the likelihood that observational studies alone will not provide clear resolution of the issue all suggest that it may be prudent to strongly consider such trials in the near future.

Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.

Wen Y; Killalea S; McGettigan P; Feely J

Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, St. James's Hospital, Dublin, Ireland.

Ir J Med Sci (IRELAND) Jul-Sep 1996, 165 (3) p210-2

Lipid peroxidation is a free radical process which is implicated in the formation of atherosclerosis. Vitamins C and E are important natural antioxidants which inhibit lipid peroxidation and a high intake of these vitamins, particularly vitamin E, is related to a reduced incidence of ischaemic heart disease. Hypertension is an independent risk factor for atherosclerosis and its relationship to antioxidant status is undetermined. In this study, we investigated free radical activity by measuring plasma malondialdehyde (MDA) using high-performance liquid chromatography (HPLC), vitamin C status measured as plasma ascorbic acid and vitamin E status measured as plasma lipid standardized alpha-tocopherol and erythrocyte alpha-tocopherol. We compared 28 patients with essential hypertension to 31 healthy subjects. Results showed that in comparison with the healthy subjects, the hypertensive patients had significantly higher plasma MDA levels (0.95 +/- 0.28 vs 0.69 +/- 0.21 mumol/l, mean +/- SD, p < 0.001) and significantly lower levels of plasma ascorbic acid (34.83 +/- 12.88 vs 51.76 +/- 13.34 mumol/L, p < 0.01). In addition, erythrocyte alpha-tocopherol concentration, which may reflect vitamin E protection in cell membranes, was significantly lower in hypertensive patients when compared with the normotensive controls (3.87 +/- 0.53 vs 4.82 +/- 1.01 mumol/l, p < 0.001), although plasma alpha-tocopherol levels were similar in the two groups (25.07 +/- 10.45 vs 23.96 +/- 6.07 mumol/l). Our results suggest that hypertensive patients may have increased lipid peroxidation and reduced protection from vitamins C and E. This may contribute to the propensity in such patients to develop atherosclerosis.

Update on dietary antioxidants and cancer.

Gaziano JM; Hennekens CH

Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204, USA.

Pathol Biol (Paris) (FRANCE) Jan 1996, 44 (1) p42-5

Advances in diagnosis and treatment of cancer, as well as increased understanding of the mechanisms of the disease, have provided and will certainly continue to provide enormous benefit to affected individuals. At the same time, interventions that may prevent common cancers from developing in healthy people could, at least in theory, afford even greater benefits to society as a whole. The hypothesis that antioxidant vitamins might reduce cancer risk is based on a large body of both basic and human epidemiologic research. A large number of case-control and cohort studies provide remarkably consistent data suggesting that consumption of foods rich in antioxidant vitamins reduce risks of developing epithelial cancers. These data raise the question of a possible role of antioxidants, such as vitamins C and E, and beta carotene, in the primary prevention of cancer as well ar cardiovascular disease but do not provide a definitive answer. Despite the lack of clear benefit, there has been a rapid increase in the consumption of supplements of these micronutrients. Limited randomized trial data on the role of supplemental antioxidants are available. A number of randomized trials are currently underway designed to test the hypothesis that antioxidants prevent chronic diseases and to evaluate the long term safety of the widespread practice of supplementation. Well designed and well conducted large-scale randomized trials are necessary to provide a definitive positive or negative result on which public policy can be based, or a null result that is truly informative and that can then safely permit the rechanneling of already limited resources to other areas of research.

Antioxidants in health and disease

Cheraskin E

School of Medicine, University of Alabama at Birmingham, USA.

J Am Optom Assoc (UNITED STATES) Jan 1996, 67 (1) p50-7

BACKGROUND: Although numerous studies have been published about the probable causes of age-related macular degeneration, arresting or preventing the disease continues to be an elusive goal. METHODS: The professional literature is reviewed to provide an overview of the relationship of the antioxidants to disorders such as heart disease, cancer, diabetes, arthritis, cataracts and macular degeneration. RESULTS: Diseases associated with aging appear to have a common denominator: oxidative damage. Antioxidants have been extensively studied to determine if they can prevent or successfully treat these diseases. CONCLUSIONS: Larger-than-recommended amounts of antioxidants need to be used earlier in life, for longer periods of time, to determine their effectiveness in arresting or preventing diseases of aging. (50 Refs.)