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ANTIOXIDANTS



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.

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Rationales for micronutrient supplementation in diabetes

Med Hypotheses. 1984 Feb. 13(2). P 139-51

Available evidence--some well-documented, some only preliminary--suggests that properly-designed nutritional insurance supplementation may have particular value in diabetes. Comprehensive micronutrient supplementation providing ample doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine, gamma-linolenic acid, and carnitine, may aid glucose tolerance, stimulate immune defenses, and promote wound healing, while reducing the risk and severity of some of the secondary complications of diabetes. Refs: 125.



Contraction and relaxation of aortas from diabetic rats: effects of chronic anti-oxidant and aminoguanidine treatments.

Naunyn Schmiedebergs Arch Pharmacol (GERMANY) Apr 1996, 353 (5) p584-91

We examined whether chronic treatment with the free radical scavengers butylated hydroxytoluene (1 g kg-1 day-1) and N-acetyl-L-cysteine (250 mg kg-1 day-1), or the inhibitor of advanced glycosylation reactions, aminoguanidine (1 g kg-1 day-1), could prevent the development of relaxation and contraction abnormalities in aorta from 2 month streptozotocin-diabetic rats. Diabetes caused a 24% deficit in maximal endothelium-dependent relaxation to acetylcholine for phenylephrine precontracted aortas (P < 0.01). This was unaffected by tissue-bath glucose concentration (5.5 or 40 mM), or by addition of 1 mM L-arginine. Butylated hydroxytoluene, N-acetyl-L-cysteine and aminoguanidine treatments gave substantial protection, maximum relaxation remaining in the non-diabetic range. Neither diabetes nor treatment affected endothelium-independent relaxation to glyceryl trinitrate. To test the suggestion that aminoguanidine could act as an inhibitor of constitutive nitric oxide synthase, acute aminoguanidine effects on endothelium-dependent relaxation to acetylcholine were also examined. No inhibition was noted. A modest increase in phenylephrine sensitivity with diabetes (P < 0.05) was unaffected by butylated hydroxytoluene or N-acetyl-L-cysteine, but partially prevented by aminoguanidine (P < 0.05). The data, therefore, provide evidence for the involvement of reactive oxygen species and the advanced glycosylation process particularly for impaired endothelium-dependent relaxation in experimental diabetes.



Antioxidant vitamins in hospitalized elderly patients: Analysed dietary intakes and biochemical status

European Journal of Clinical Nutrition (United Kingdom), 1996, 50/7 (473-478)

Design: Descriptive study. Setting: Geriatric department of the Grenoble University Hospital. Subjects: 24 hospitalized elderly women: 13 long-stay patients and 11 in rehabilitation after femoral neck fracture. Main outcome measures: Retinol, carotene, tocopherol and vitamin C dietary intakes were evaluated by 5-day duplicate portion analysis. Circulating levels of retinol, beta-carotene, alpha-tocopherol and vitamin C were determined in parallel (HPLC). Results: Mean intake of vitamin C (21 mg/d), and vitamin E (3.1 mg alpha-tocopherol equivalents TE/d) were low compared to recommendations, in relation with poor energy intake (5.27 MJ/d) and nutrient densities. More than 85% of the patients exhibited vitamin C and vitamin E intakes below two-thirds the recommendations (60 mg/d and 10 mg TE/d, respectively) and 50% did not meet recommendations for vitamin A (800 microg retinol equivalents/d). With the exception of retinol, dietary vitamin intakes were positively correlated to corresponding blood concentrations. No values below cut-off levels were found concerning plasma retinol, plasma tocopherol or ratio of alpha-tocopherol to cholesterol. In contrast, 26% and 32% of the elderly patients had low circulating levels of beta-carotene and vitamin C, respectively. Conclusions: The present study highlights low antioxidant vitamin intakes, particularly concerning vitamin E and vitamin C, and an important proportion of low blood vitamin C and beta-carotene concentrations in hospitalized elderly women. Further studies are needed to determine the actual requirements of hospitalized elderly patients and to evaluate the potential benefits of providing micronutrient-enriched foods to this population.



Antioxidant depletion, lipid peroxidation, and impairment of calcium transport induced by air-blast overpressure in rat lungs

Experimental Lung Research (USA), 1996, 22/2 (179-200)

Exposure to blast overpressure, or the sudden rise in atmospheric pressure after explosive detonation, results in damage mainly of the gas-filled organs. In addition to the physical damage, in the lung, injury may proceed via a hemorrhage-dependent mechanism initiating oxidative stress and accumulation of lipid peroxidation products. Massive rupture of capillaries and red blood cells, release of hemoglobin, its oxidation to met-hemoglobin and degradation sets the stage for heme-catalyzed oxidations. The authors hypothesized that lipid hydroperoxides interact with met-hemoglobin in the lungs of exposed animals to produce ferryl-hemoglobin, an extremely potent oxidant that induces oxidative damage by depleting antioxidants and initiating peroxidation reactions. Oxidation-induced disturbance of Ca2+ homeostasis facilitates further amplification of the damage. To test this hypothesis, groups of anesthetized rats (6 rats/group) were exposed to blast at 3 peak pressures: low (61.2 kPa), medium (95.2 kPa), high (136 kPa). One group served as an unexposed control. Immediately after exposure, the rats were euthanized and the lungs were analyzed for biochemical parameters. Blast overpressure caused: (1) depletion of total and water-soluble pulmonary antioxidant reserves and individual antioxidants (ascorbate, vitamin E, GSH), (2) accumulation of lipid peroxidation products (conjugated dienes, TBARS), and (3) inhibition of ATP-dependent Ca2+ transport. The magnitude of these changes in the lungs was proportional to the peak blast overpressure. Inhibition of Ca2+ transport strongly correlated with both depletion of antioxidants and enhancement of lipid peroxidation. In model experiments, met-hemoglobin/H2O2 produced damage to Ca2+ transport in the lungs from control animals similar to that observed in the lungs from blast overpressure-exposed animals. Ascorbate, which is known to reduce ferryl- hemoglobin, protected against met-hemoglobin/H2O2-induced damage of Ca2+ transport. If ferryl-hemoglobin is the major reactive oxygen species released by hemorrhage, then its specific reductants (e.g., nitric oxide) along with other antioxidants may be beneficial protectants against pulmonary barotrauma.



The use of antioxidants in healing

Dermatologic Surgery (USA), 1996, 22/2 (156-160)

BACKGROUND. Antioxidants enhance the healing of infected and noninfected wounds by reducing the damage caused by oxygen radicals. OBJECTIVE. Studies were conducted to determine if the CRT components (vitamin E, sodium pyruvate, and specific fatty acids) could synergistically enhance healing. METHODS. In vitro and in vivo studies were used to assess the effect of various combination of CRT components. RESULTS. CRT reduced oxidative damage to keratinocytes and monocytes exposed to ultraviolet light and toxic chemicals and provided protection to human subjects exposed to ultraviolet irradiation. CRT dramatically facilitated healing of infected and noninfected wounds. In herpes-infected guinea pigs, CRT reduced vaginal viral lesion development, severity, and duration, thus facilitated healing of the lesions. CRT also reversed doxorubicin cytotoxicity in monocytes and reversed doxorubicin-impaired wound healing in rats. CONCLUSION: The CRT colly to enhancing healing of injuries.



Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids.

J Am Diet Assoc (UNITED STATES) Jul 1996, 96 (7) p693-702; quiz 703-4

Under normal circumstances, free radicals that are produced through biological processes and in response to exogenous stimuli are controlled by various enzymes and antioxidants in the body. Laboratory evidence suggests that oxidative stress, which occurs when free radical formation exceeds the ability to protect against them, may form the biological basis of several acute medical problems, such as tissue injury after trauma, and chronic conditions, such as atherosclerosis and cancer. A potential role for the antioxidant micronutrients (vitamin C, vitamin E, and the carotenoids) in modifying the risk for conditions that may result from oxidative stress has stimulated intense research efforts, increased interest in micronutrient supplements, and heightened consumer interest in these compounds. Much remains to be learned, however, about the bioavailability, tissue uptake, metabolism, and biological activities of these micronutrients. These biological characteristics will ultimately determine their clinical usefulness in modulating oxidative stress. Also, whether the antioxidant mechanism explains their relationship with risk for acute and chronic disease in epidemiologic studies remains to be determined. Increased knowledge in this area of nutrition science will have an impact on both clinical dietetics practice and public health nutrition guidelines.



Dietary intake and plasma levels of antioxidant vitamins in health and disease: A hospital-based case-control study

India Journal of Nutritional and Environmental Medicine (United Kingdom)

1995, 5/3 (235-242)

Of 1667 subjects that attended the hospital, 1335 were patients with diagnosed medical conditions, together with 202 randomly selected apparently healthy controls from the same population, were studied in detail for demographic variables, dietary and biochemical data. Dietary consumption of antioxidant vitamins A, E, and C and beta-carotene and soluble fibre was lower in the majority of conditions compared to controls. Plasma concentrations of vitamin C and beta-carotene were significantly lower in all patient groups. Reduced vitamin E levels were noted in patients with cardiovascular diseases, stroke, Parkinson's disease, chronic renal failure, nephrotic syndrome, type A behaviour, post-partum psychosis, burns, liver diseases, cancer, rheumatoid arthritis and aluminium phosphide poisoning. Lipid peroxides (thiobarbituric acid reactive substances), which are an indicator of oxygen-derived free radical damage, were significantly higher than controls in most conditions and marginally higher in respiratory and psychiatric conditions. Lipid peroxides levels were much greater over all in acute myocardial infarction, cancer, stroke, nephrotic syndrome, chronic renal failure, liver diseases, post-partum psychosis, pregnancy, burns and aluminium phosphide poisoning. Pool dietary intake alone does not explain the decreases in plasma levels of antioxidants and increases in lipid peroxides. Decreases may also be due to increased demands for antioxidants to counter free radical damage.



Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction

European Heart Journal (United Kingdom), 1995, 16/8 (1044-1049)

Clinical studies suggest that neutrophil activation during acute myocardial infarction (MI) aggravates tissue injury. Activated neutrophils are an important source of oxygen free radicals (OFR), the injurious effects of which are counteracted by endogenous antioxidants. We have previously shown in healthy subjects that supplementation with antioxidant vitamins C and E suppresses OFR production by isolated neutrophils assayed by chemiluminescence (CL). the present study, performed in patients with acute MI aimed (1) to investigate the effect of vitamin C and E supplementation upon neutrophil OFR production and serum lipid peroxides, (2) to evaluate serum levels of vitamins C and E in the course of MI. Forty-five patients with acute MI were randomized to receive either conventional treatment plus vitamin C and E aa 600 mg.day-1 p.o. for 14 days (VIT,n=23) or conventional treatment only (control, n=22). All measurements were performed on the 1st and 14th day. Neutrophil OFR production assayed by CL decreased significantly in VIT patients (Wilcoxon test for paired data P<0.01, Chi square test P<0.01). In the control group, changes in OFR production were not significant. Serum lipid peroxides (measured as TBARS) increased in controls (P<0.05), but remained stable in VIT patients. Mean (plus or minusSE) serum ascorbic acid and tocopherol on the 1st day were 0.43 plus or minus 0.18mg% and 3.25 plus or minus 1.32 microM.mM -1 cholesterol, respectively, in all patients. On the 14th day in non-supplemented patients mean tocopherol was unchanged, whereas ascorbic acid increased significantly (0.63 plus or minus 0.24 mg%, P<0.01) suggesting that a low basal level was associated at least in part with the acute phase of the disease. An expected increase in serum vitamin levels occurred in VIT patients. In conclusion, supplementation with vitamins C and E suppresses neutrophil OFR production and lowers the marker of lipid peroxidation in patients with MI. These effects, together with a deficiency of antioxidant vitamins, particularly vitamin C in the early phase of the disease, support the view that supplementation with antioxidant vitamins is advisable in patients with MI.



Antioxidant therapy using high dose vitamin C: Reduction of postburn resuscitation fluid volume requirements

World Journal of Surgery (USA), 1995, 19/2 (287-291)

Twenty-four guinea pigs with third degree burns over 70% of the body surface area were divided equally into four groups. At 0.5 hours postburn, all groups received Ringer's lactate solution (R/L) according to the Parkland formula. The infusion rate was then reduced to 25% of the Parkland formula at 1.5 hours postburn. Group 1 received only R/L, and groups 2, 3 and 4 received adjuvant vitamin C (14.2 mg/kg/hr) until 4, 8, and 24 hours postburn, respectively. The volume of R/L was reduced by that of vitamin C solution so that the hourly sodium and fluid intake in each group was the same. Groups 1 and 2 demonstrated higher hematocrit and lower cardiac output values than did group 3, suggesting hypovolemia and hemoconcentration in these groups. Group 3 showed hematocrit and cardiac output values equivalent to those in group 4. We conclude that high dose vitamin C infusion maintains hemodynamic stability in the presence of a reduced resuscitation fluid volume provided vitamin C is administered for a minimum of 8 hours postburn.



Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise

EUR. J. APPL. PHYSIOL. OCCUP. PHYSIOL. (Germany), 1993, 67/5 (426-430)

This study investigated the effects of antioxidant vitamin supplementation upon muscle contractile function following eccentric exercise and was performed double blind. Twenty-four physically active young subjects ingested either placebo (400 mg; n = 8), vitamin E (400 mg; n = 8) or vitamin C (400 mg; n = 8) for 21 days prior to and for 7 days after performing 60 min of box-stepping exercise. Contractile function of the triceps surae was assessed by the measurement of maximal voluntary contraction (MVC) and the ratio of the force generated at 20 Hz and 50 Hz tetanic stimulation before and after eccentric exercise and for 7 days during recovery. Following eccentric exercise, MVC decreased to 75 (4)% (mean (SE); n = 24; P < 0.05) of the preexercise values and the 20/50 Hz ratio of tetanic tension from 0.76 (0.01) to 0.49 (0.03) (mean (SE); n = 24; P < 0.05). Compared to the placebo group no significant changes in MVC were observed immediately post-exercise, though recovery of MVC in the first 24 h post-exercise was greater in the group supplemented with vitamin C. The decrease in 20/50 Hz ratio of tetanic tension was significantly less (P < 0.05) postexercise and in the initial phase of recovery in subjects supplemented with vitamin C but not with vitamin E. These data suggest that prior vitamin C supplementation may exert a protective effect against eccentric exercise-induced muscle damage.



Modification of the daily photoreceptor membrane shedding response in vitro by antioxidants

INVEST. OPHTHALMOL. VISUAL SCI. (USA), 1992, 33/10 (3005-3008)

The shedding of rod outer segment disc membrane was investigated in a commonly used frog eyecup preparation, with respect to length of time in vitro. It was found that the amplitude, but not the timing, of the 'dawn' (ie, when the lights are turned on) shedding response was increased threefold if the time in vitro was increased from 1.5-2 hr to 12-13 hr before dawn. After the overnight incubation, morphologic deterioration of the photoreceptors was not apparent by light or electron microscopy. The addition of the antioxidants, vitamin C or alpha-tocopherol (vitamin E), inhibited the increase in shedding, suggesting that it was induced by oxidation. These results help define conditions necessary for the maintenance of normal retinal metabolism in vitro. They also suggest a link between the amplitude of the dawn disc membrane shedding response and oxidation.



Tirilazad mesylate protects vitamins C and E in brain ischemia-reperfusion injury

J. NEUROCHEM. (USA), 1992, 58/6 (2263-2268)

Brain concentrations of the antioxidant vitamins C and E decreased following unilateral carotid occlusion and reperfusion for 2 or 24 h in gerbils. Administration of the 21-aminosteroid inhibitor of lipid peroxidation, tirilazad mesylate (U74006F), prevented the decrease in level of both of these vitamins following 2 h of reperfusion. After 24 h of reperfusion, however, alpha-tocopherol (vitamin E) continued to be protected, but ascorbic acid (vitamin C) showed a pronounced decrease in content. The changes in concentrations of these vitamins are consistent with U74006F acting to inhibit peroxidation in the CNS by scavenging of lipid peroxyl radicals and suggest that, in the presence of this agent, injury-induced depletion of ascorbic acid may occur without irreversible tissue damage.



Biochemical basis of ozone toxicity

FREE RADIC. BIOL. MED. (USA), 1990, 9/3 (245-265)

Ozone (O3) is the major oxidant of photochemical smog. Its biological effect is attributed to its ability to cause oxidation or peroxidation of biomolecules directly and/or via free radical reactions. A sequence of events may include lipid peroxidation and loss of functional groups of enzymes, alteration of membrane permeability, and cell injury or death. An acute exposure to O3 causes lung injury involving the ciliated cell in the airways and the type 1 epithelial cell in the alveolar region. The effects are particularly localized at the junction of terminal bronchioles and alveolar ducts, as evident from a loss of cells and accumulation of inflammatory cells. In a typical short-term exposure the lung tissue response is biphasic: an initial injury-phase characterized by cell damage and loss of enzyme activities, followed by a repair-phase associated with increased metabolic activities, which coincide with a proliferation of metabolically active cells, for example, the alveolar type 2 cells and the bronchiolar Clara cells. A chronic exposure to O3 can cause or exacerbate lung diseases, including perhaps an increased lung tumor incidence in susceptible animal models. Ozone exposure also causes extrapulmonary effects involving the blood, spleen, central nervous system, and other organs. A combination of O3 and NO2, both of which occur in photochemical smog, can produce effects which may be additive or synergistic. A synergistic lung injury occurs possibly due to a formation of more powerful radicals and chemical intermediates. Dietary antioxidants, for example, vitamin E, vitamin C, and selenium, can offer a protection against O3 effects.



Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats

USA NEUROSCI. LETT. (Netherlands), 1990, 108/1-2 (201-206)

Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to delayed tissue damage following traumatic spinal cord injury (SCI). Ubiquinols (reduced coenzyme Q), ascorbate (vitamin C), and alpha-tocopherol (vitamin E) are endogenous antioxidants; decreases in tissue levels of these compounds may, therefore, reflect ongoing oxidative reactions. In the present studies, alterations in tissue levels of ubiquinol-9 and -10, ascorbate, and alpha-tocopherol were examined after SCI of varying severity in the rat. Levels of alpha-tocopherol did not change significantly after injury. Ascorbate and ubiquinol levels were decreased after trauma. Changes in tissue levels of ubiquinol, but not ascorbate reflected the degree of trauma. Thus, ubiquinol levels may provide a useful marker of the oxidative component of the secondary injury response.



An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes

ARCH. BIOCHEM. BIOPHYS. (USA), 1990, 283/2 (234-240)

Since antioxidants have been shown to play a major role in preventing some of the effects of aging and photoaging in skin, it is important to study this phenomenon in a controlled manner. This was accomplished by developing a simple and reliable in vitro technique to assay antioxidant efficacy. Inhibition of peroxidation by antioxidants was used as a measure of relative antioxidant potential. Liposomes, high in polyunsaturated fatty acids (PUFA), were dispersed in buffer and irradiated with ultraviolet (UV) light. Irradiated liposomes exhibited a significantly higher amount of hydroperoxides than liposomes containing antioxidants in a dose- and concentration-dependent manner. Lipid peroxidation was determined spectrophotometrically by an increase in thiobarbituric acid reacting substances. To further substantiate the production of lipid peroxides, gas chromatography was used to measure a decrease in PUFA substrate. In order of decreasing antioxidant effectiveness, the following results were found among lipophilic antioxidants: BHA > catechin > BHT > alpha-tocopherol > chlorogenic acid. Among hydrophilic antioxidants, ascorbic acid and dithiothreitol were effective while glutathione was ineffective. In addition, ascorbic acid was observed to act synergistically with alpha-tocopherol, which is in agreement with other published reports on the interaction of these two antioxidants. Although peroxyl radical scavengers seem to be at a selective advantage in this liposomal/UV system, these results demonstrate the validity of this technique as an assay for measuring an antioxidant's potential to inhibit UV-induced peroxidation.



Antioxidants, fat and skin cancer

Skin Cancer (Portugal), 1995, 10/2 (97-101)

The incidence of actinic keratoses, basal cell carcinomas and squamous cell carcinomas increases proportionately with increasing cutaneous sun exposure. There is mounting evidence that dietary nutrients may play an important role in sun induced skin damage and skin cancer. In this brief discussion, the evidence is reviewed for a participatory interaction between ultraviolet radiation and dietary factors in cutaneous aging and carcinogenesis. In particular, this paper investigates the relationship between dietary antioxidants and cutaneous fat concentrations as the keys to understanding the possible relationship between diet and skin cancer.



Photoprotective effect of superoxide scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse

Photodermatology Photoimmunology Photomedicine (Denmark), 1990, 7/2 (56-62)

Albino hairless mice (Skh: HR-1) exposed chronically to suberythemal doses of ultraviolet radiation develop visible skin changes, histological alterations, and tumors. Topical treatment of mice with solutions of superoxide-scavening antioxidants (such as alpha-tocopherol, ascorbic acid, propyl gallate and Trolox (R)) prior to each UVB radiation exposure reduced significantly the severity of these events. Tocopherol esters and ascorbyl palmitate were not as effective as the parent compounds in providing protection. The data suggest a role for superoxide in UVB radiation-induced skin photoaging and the protective potential of super oxide scavengers. In contrast, the severity of UVA radiation-induced mouse skin damage was not reduced by topical application of the antioxidants tested here.



Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation

J. INVEST. DERMATOL. (USA), 1989, 93/6 (769-773)

Antioxidants may play a significant role in ameliorating or preventing photobiologic damage in skin that could lead to cutaneous disorders such as cancer and premature aging. The objective of this study was to assess the acute cutaneous enzymic and nonenzymic antioxidant response to a single exposure of large fluence (300 mJ/cm2) ultraviolet radiation (>280 nm) in hairless mice. This treatment caused an immediate and statistically significant inhibition of glutathione reductase and catalase activity. Glutathione peroxidase and superoxide dismutase were not affected. Glutathione levels decreased and, conversely glutathione disulfide concentrations increased. A slight depletion of the total glutathione was observed, while the content of total ascorbic acid did not change. The lipophilic antioxidants alpha-tocopherol, ubiquinol 9 and ubiquinone 9 also decreased significantly, and the concentration of malondialdehyde remained constant. The free radical scavenging activity of epidermis, as assessed by reduction of the stable, cationic nitroxide radical (2,2,6,6-tetramethyl-1-piperidinoxy-4-(2',4',6'-trimethyl) methyl-pyridinium perchlorate) was considerably inhibited. The study indicates that immediately after exposure to a large fluence of ultraviolet radiation the enzymic and nonenzymic antioxidant capacity of skin decreases significantly.



Diminished production of malondialdehyde after carotid artery surgery as a result of vitamin administration

Medical Science Research (United Kingdom), 1996, 24/11 (777-780)

The objective of this study was to establish the antioxidative effect of the vitamins E, C and retinyl palmitate (vitamin A), contained in a multivitamin solution, in carotid artery revascularisation surgery. 57 patients, 67.84 plus or minus 5.72 years of age, 39 men and 18 women, were divided into a control group (27 subjects) and a group with 30 subjects (mean age 68.46 plus or minus 5.09 years) who received the vitamin treatment immediately before the start of reperfusion of the brain. The control group (mean age 67.14 plus or minus 6.37 years) received physiological sodium chloride as placebo. All of the patients suffered from ischaemic cerebrovascular insufficiency manifested as TIA (transitory ischaemic attack) due to haemodynamically significant stenosis of the extracranial part of the ICA (internal carotid artery). Oxidative burst was measured by malondialdehyde (MDA) - thiobarbituric acid reactive substances (TBARS) perioperatively before and 0.5, 1, 2 and 3 h after revascularisation. In the control group MDA-TBARS significantly increased from 0.91 plus or minus 0.49 to 1.15 plus or minus 0.41 nmol mL-1 (p < 0.003) 1 h after reperfusion onset and returned to baseline after 2-3 h. In the vitamin-treated group MDA-TBARS steadily decreased during the reperfusion period (1.11 plus or minus 0.39, 0.91 plus or minus 0.42, 0.81 plus or minus 0.29, 0.78 plus or minus 0.39, 0.72 plus or minus 0.24 nmol mL-1). The significant difference in MDA-TBARS between control and treatment groups, 1 h after the start at reperfusion was 1.15 plus or minus 0.41 vs 0.81 plus or minus 0.29 nmol mL-1; (p < 0.001). As an indirect parameter of reperfusion injury 13% (4/30 patients) of the patients in thetreatment group suffered... The perioperative use of antihypertensive drugs was 20% (6/30) in the treatment group, as compared to 78% (21/27) in the control group. These results suggests that vitamin treatment prior to reperfusion might be of beneficial effect, alleviating lipid peroxidation and leading to a better clinical course as regards the central nervous system.



Spermine partially normalizes in vivo antioxidant defense potential in certain brain regions in transiently hypoperfused rat brain

Neurochemical Research (USA), 1996, 21/12 (1497-1503)

Activities of the antioxidant enzymes such as superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) as well as the level of reduced glutathione and the concentration of thiobarbituric acid-reactive substance (TBARS) in brain regions in transiently hypoperfused rat brain with or without intravenous infusion of spermine were evaluated. Cerebral hypoperfusion was induced by temporary occlusion of common carotid arteries for 30 min and subsequently, by reperfusion for 60 min. Infusion of spermine reversed the decrease in SOD activity in the cerebral cortex, striatum, hippocampus, hypothalamus and midbrain, and amounted to 50.1 U, 61.5 U, 50.3 U, 30.0 U, 38.0 U, respectively, while GSH-Px restored to normal values only in the cerebral cortex and striatum and amountter use of spermine no changes in GSSG-R were seen in the hypothalamus and midbrain. The activity of GSSG-R was in accordance with the control for the striatum and amounted to 39.0 IU after using spermine, GSH content returned to normal values in the striatum and midbrain after i.v. use of spermine and amounted to 210 and 240 nmol/g of wet tissue, respectively. In addition, the production of TBARS dropped markedly (P < 0.05) in the hippocampus and midbrain and amounted to 100 and 105 micromol/g of wet tissue, respectively. Partially beneficial effect of spermine could result from the inhibition of free radical generation and capability of chelate formation with iron ions.



Positron-labeled antioxidant 6-deoxy-6-(18F)fluoro-L-ascorbic acid: Increased uptake in transient global ischemic rat brain

Nuclear Medicine and Biology (USA), 1996, 23/4 (479-486)

The in vivo uptake and distribution of 6-deoxy-6-(18F)fluoro-L-ascorbic acid (18F-DFA) were investigated in rat brains following postischemic reperfusion. Global cerebral ischemia was induced in male Wistar rats for 20 min by occlusion of four major arteries. Two time paints were chosen for 18F-DFA injection to rats subjected to cerebral ischemia, at the start of recirculation and 5 days following recirculation. The rats were then killed at 2 h after tail-vein administration of 18F-DFA and tissue radioactivity concentration was determined. Increased uptake of radioactivity in particular brain regions, including the cerebral cortex, hypothalamus, and amygdala following injection of 18F-DFA, compared to the sham operated control, was observed 5 days after reperfusion. Similar results were also obtained in in vitro experiments using brain slices. Abnormal in v45Ca, a marker of regional postischemic injury, was observed in these brain regions in tissue dissection experiments. Furthermore, metabolite analysis of nonradioactive DFA using 19F-NMR showed that DFA remained intact in the postischemic reperfusion brain. The present results indicate that 18F-DFA increasingly accumulates in damaged regions of postischemic reperfusion brain.



Maternal infusion of antioxidants (Trolox and ascorbic acid) protects the fetal heart in rabbit fetal hypoxia

Division of Neonatology, 525 NHB, Birming (USA), 1996, 39/3 (499-503)

The antioxidants, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2 carboxylic acid, a water soluble analog of vitamin E) and ascorbic acid (AA), protect the heart from ischemia-reperfusion injury. We hypothesized that maternal infusion of Trolox and AA, would reduce the fetal bradycardia and myocardial damage observed in fetal hypoxia and increase the total antioxidant activity in fetal plasma. Either i.v. saline (control group) or Trolox + AA (drug group) was randomly administered to 29 d-old pregnant rabbits. Fetal hypoxia was induced by uterine ischemia. Fetal heart rate, plasma CK-MB activity, and plasma total radical antioxidant potential (TRAP) were measured in different sets of animals. Fetal heart rate in the drug group was higher than in the control group for the first 35 min (p < 0.05 at every 5-min interval). Fetal bradycardia (<60 beats/min) occurred after 39 min (median) in the drug group, and 29 min in the control group (p < 0.05). After 50 min of hypoxia, plasma CK-MB was lower in the drug group, 1204 plus or minus 132 U/L (mean plus or minus SEM), than in the control group, 2633 plus or minus 233 U/L (p < 0.05), TRAP was higher in the drug group, 3.01 plus or minus 0.15 mM (Trolox equivalent concentration), than in the control group, 1.48 plus or minus 0.27 mM (p < 0.05). Higher TRAP levels (greater than or equal to2.0 mM) were associated with lower CK-MB levels (<2500 U/L) (p < 0.05). Administration of Trolox and AA to the mother has a beneficial effect on fetal myocardial damage after fetal hypoxia, and a small beneficial effect on fetal bradycardia during hypoxia. The beneficial effect may be due to the augmentation of fetal plasma antioxidants from maternal antioxidant pretreatment.



Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study

CLIN. INVEST. (Germany), 1993, 71/1 (3-6)

Previous cross-cultural comparisons of the mortality from ischemic heart disease in European communities with associated plasma levels of essential antioxidants have revealed strong inverse correlations for vitamin E and relatively weak correlations for other antioxidants. Similarly, in a case-control study in Edinburgh low plasma levels of vitamin E were significantly associated with an increased risk of previously undiagnosed angina pectoris whereas low levels of other essential antioxidants lacked statistical significance. The current Basel Prospective Study is particularly well suited to elucidate the impact of antioxidants other than vitamin E. In this population (which was recently evaluated regarding cancer mortality) the plasma levels of vitamins E and A are exceptionally high and above the presumed threshold level of risk for ischemic heart disease. The present 12-year follow-up of cardiovascular mortality in this study reveals a significantly increased relative risk of ischemic heart disease and stroke at initially low plasma levels of carotene (< 0.23 micromol/l) and/or vitamin C (< 22.7 micromol/l), independently of vitamin E and of the classical cardiovascular risk factors. Low levels of both carotene and vitamin C increase the risk further, in the case of stroke even with significance for overmultiplicative interaction. In conclusion, in cardiovascular disease independent inverse correlations may exist for every major essential antioxidant although the latter can also interact synergistically. Therefore future intervention trials of antioxidants in the prevention of ischemic heart disease should primarily test the simultaneous optimization of the status of all principal essential antioxidants.



Antioxidant vitamins and disease - Risks of a suboptimal supply

THER. UMSCH. (Switzerland), 1994, 51/7 (467-474)

Reactive oxygen species (ROS) such as the superoxide (O2.-) and the hydroxyl radical (OH.) are aggressive chemical compounds that can induce tissue injury, e.g. by peroxidation of polyunsaturated fatty acids in cell membranes or directly by DNA damage. Many pathological conditions are in part caused by ROS. There are various biological defense systems directed towards radicals: specific enzymes, e.g. superoxide dismutase or glutathion peroxidase; nonessential antioxidants, e.g. the plasma proteins and uric acid; and the essential antioxidants, e.g. vitamin C, vitamin D and carotenoids. This review focuses on various clinical conditions where ROS are of major pathogenetic significance: ageing, cancer, stroke, hematologic disorders, adult respiratory distress syndrome (ARDS) and organ preservation in transplantation medicine. Moreover, the complementary system of the vitamins C and E in defense against ROS is shortly discussed and the need for further studies about the effects of antioxidant treatment, such as interventional studies, proposed. The chronic exposure of the organism to ROS is an important factor for tissue injury in the process of ageing. Lipofuscin is a typical product of lipid peroxidation and inversely correlates with longevity of an organism. The ingestion of higher doses of antioxidative vitamins was recently shown to be protective for the development of cataracts, a degenerative disorder of the eye. The impairment of the immune system in elderly people might be prevented by a higher intake of multivitamin supplements. Whether supplementation with antioxidative vitamins can extend the life span in humans, as was shown in experimental animals, remains unanswered. High intake of vegetables and fruits is associated with a significantly lower incidence of cancer, in particular of lung, but also of laryngeal, esophageal and colorectal cancer, which might be attributed to higher intake of antioxidant vitamins. As discussed in this issue of the journal by Gey et al., there is an inverse correlation between plasma status of antioxidant vitamins and coronary mortality due to prevention of atherosclerosis. There is also an inverse correlation between the risk of suffering from a fatal stroke and the plasma concentrations of antioxidant vitamins. Supplementation with vitamin E in some hematologic disorders such as beta-thalassemia and glucose-6-phosphatase-dehydrogenase deficiency showed an improvement of hemolysis. ARDS, a common cause of respiratory failure in severly ill patients, is a 'classical free radical disease'. Interventional studies with antioxidant vitamins for the treatment of ARDS are so far lacking. Reperfusion injury by a 'radical burst' may be a major cause for performance of organ transplants such as the kidney. The treatment with multivitamin preparations containing vitamin C and E was associated with better transplant performance in kidney transplants in a recent study. In conclusion, 'optimal' plasma concentrations of essential antioxidants are a primary aim in the prevention of disease such as ischemic heart disease, stroke and cancer. This is achieved by intake of higher doses of dietary antioxidants (as compared with RDAs) or, if necessary, by vitamin supplements.



Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: An epidemiological update with special attention to carotene and vitamin C

AM. J. CLIN. NUTR. (USA), 1993, 57/5 SUPPL. (787S-797S)

For the prolongation of life expectancy and reduction of ischemic heart disease (IHD) dietary guidelines generally recommend lowering saturated mammalian fat with partial replacement by vegetable oils and increasing generously vegetables, legumes, and fruits, which provide more essential antioxidants. Plasma antioxidants as assayed in epidemiological studies of complementary type (ie the cross-cultural MONICA Vitamin Substudy reevaluation considering the 'Finland-Factor', the Edinburgh Angina-Control Study, and the Basel Prospective Study) consistently revealed an increased risk of IHD (and stroke) at low plasma concentrations of antioxidants, with the rank order as follows: lipid-standardized vitamin E >> carotene = vitamin C > vitamin A, independently of classical IHD risk factors. Decreasing IHD risk through nutrition may be possible when plasma concentrations have the following val ues: > 27.5-30.0 micromol vitamin E/L, 0.4-0.5 micromol carotene/L, 40-50 micromol vitamin C/L and 2.2-2.8 micromol vitamin A/L. Thus, previous prudent regimens may now be updated, aiming at an optimal status of all essential and synergistically linked antioxidants.



Oxidative protein damage in human diabetic eye: evidnal participation.

Eur J Clin Invest (ENGLAND) Feb 1997, 27 (2) p141-7

Considerable evidence indicates that the maintenance of protein redox status is of fundamental importance for cell function, whereas structural changes in proteins are considered to be among the molecular mechanisms leading to diabetic complications. In this study, protein redox status and antioxidant activity were investigated in the lens and vitreous of diabetic and nondiabetic subjects. A significantly lower content of sulphydryl proteins was found in lens and vitreous of diabetic patients than in those of non-diabetic and control subjects. Moreover, an increased formation of protein-bound free sulphydryls and carbonyl proteins, indices of oxidative damage to proteins, was noted in diabetic patients. All these parameters were shown to be altered particularly when diabetes was complicated with retinal alterations. In addition, glutathione peroxidase activity and ascorbic acid levels, known to exert important antioxidant functions in the eye compartment, were found to be significantly decreased in the lens of diabetic patients, especially in the presence of retinal damage. This study indicates an alteration of protein redox status in subjects affected by diabetes mellitus; lens and vitreous proteins were found to be oxidized to a greater extent in the presence of retinal disease, together with a marked decrease of eye antioxidant systems. These results suggest that oxidative events are involved in the onset of diabetic eye complications, in which the decrease in free radical scavengers was shown to be associated with the oxidation of vitreous and lens proteins. Protein oxidation may, therefore, represent an important mechanism in the onset of eye complications in diabetic patients.



Abnormalities in diabetes or experimental galactosemia. IV. Antioxidant defense system.

Free Radic Biol Med (UNITED STATES) 1997, 22 (4) p587-92

Activities of enzymes that protect the retina from reactive oxygen species were investigated in experimentally diabetic rats and experimentally galactosemic rats, two animal models known to develop vascular lesions consistent with diabetic retinopathy. Diabetes or experimental galactosemia of 2 months duration significantly decreased the activities of glutathione reductase and glutathione peroxidase in the retina while having no effect on the glutathione synthesizing enzymes glutathione synthetase and gamma-glutamyl cysteine synthetase. Activities of two other important antioxidant defense enzymes-superoxide dismutase (SOD) and catalase-also were decreased (by more than 25%) in retinas of diabetic rats and galactosemic rats. Administration of supplemental antioxidants, vitamins C and E, for the 2 months prevented the diabetes-induced impairment of antioxidant defense system in the retina. In experimentally galactosemic rats, the supplemental antioxidants were not as effective: SOD activity was normalized, but the enzymes of the glutathione redox cycle were only partly restored, and the subnormal catalase activity was unaffected. Diabetes or experimental galactosemia results in significant impairment of the antioxidant defense system in the retina, and exogenous antioxidant supplementation can help alleviate the subnormal activities of antioxidant defense enzymes.



Nutritional antioxidants, red cell membrane fluidity and blood viscosity in type 1 (insulin dependent) diabetes mellitus.

Diabet Med (ENGLAND) Dec 1996, 13 (12) p1044-50

The study was designed to evaluate whether the antioxidant nutrients selenium, vitamin A, and vitamin E are associated with alterations of blood viscosity in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). We assessed selenium concentrations in plasma and red blood cells (RBC), glutathione peroxidase activity in RBC, vitamin A and vitamin E, and the viscosity of whole blood and plasma in 20 patients with IDDM and 20 sex, age and body mass index-matched healthy controls. While selenium was not altered in plasma in IDDM, it was markedly decreased in RBC of IDDM (1.24 +/- 0.32 vs 0.92 +/- 0.38 mumol l-1, p = 0.006) correlating negatively with the elastic and viscous component of whole blood viscosity. Plasma viscosity increased with stage of retinopathy. Mean glutathione peroxidase activity in RBC was reduced in IDDM (5.78 +/- 0.77 vs 5.13 +/- 1.03 U gHb-1, p = 0.029). In IDDM with normal renal function (creatinine < or = 97.2 mumol l-1, no albuminuria) vitamin A was significantly reduced (1.26 +/- 0.62 vs 1.89 +/- 0.56 mumol l-1, p = 0.005). Vitamin A levels increased with impaired renal function. They strongly correlated with plasma creatinine (r = 0.86, p < 0.001) and plasma viscosity (r = 0.71, p = 0.001). However, in vitro experiments with different vitamin A plasma concentrations indicated that this particular correlation may not represent a causal one. No changes in vitamin E were found in IDDM. We conclude that reduced selenium concentrations in RBC contribute to impaired haemorheology in IDDM patients. Plasma viscosity was not affected by the plasma concentrations of vitamins A and E.



[Prospective biochemical study of the antioxidant defense capacity in retinopathy of premokemiai vizsgalata retinopathia preamaturorumban.

Orv Hetil (HUNGARY) Jan 26 1997, 138 (4) p201-5

The study was carried out on 60 oxygen-treated premature infants weighed less than 2000 g (1529 +/- 302 g, x mean +/- S. D.) and on their mothers. Both the Retinopathy of Prematurity screening and the biochemical tests were started at the age of 6 weeks. According to our results, the signs of an acute oxidative stress could be seen in all 60 oxygen-treated prematures erythrocyte's glutathione redox system, independently of the presence of the retinopathy compared to prematures (n = 20) with the same gestational age but without oxygen therapy (1720 +/- 305 g, mean +/- S.D.). The concentrations of free sulfhydril groups in the plasma, and the blood selenium levels were significantly lower in the prematures suffering from moderate retinopathy (n = 5) than in the other oxygen-treated premature without retinopathy (n = 27) and with "any retinopathy" (n = 28) patients groups. The same tendency was seen in the mothers. Vitamin E treatment of "any retinopathy" infants seemed to have a positive effect against the development of Retinopathy of Prematurity. The close correlation found between the antioxidant capacity of the mothers and babies suggest that the supplementation of feeding with sulfur-containing amino acids (methionine, cysteine) during pregnancy would improve the antioxidant capacity of prematures. An antioxidant cocktail (selenium + vitamin E) given to the high-risk mothers (advanced age, smoking, pregnancy-induced hypertension) before delivery as suggested in literature might be useful in prevention of Retinopathy of Prematurity. (47 Refs.)



[Antioxidants for prophylaxis of eye diseases]

Klin Oczna (POLAND) Feb 1996, 98 (2) p141-3

The contemporary literature has widely described the role of free oxygen radicals and their antioxidants in pathogenesis of some eye diseases, mainly cataract, age-related macular degeneration, retinopathy of prematurity and cystic macular oedema. This paper presents publications which stress the importance of antioxidants use in prophylaxis of cataract and age-related macular degeneration. Positive antioxidants role was proved both in experimental research and in clinical observations. (29 Refs.)



[Erythrocyte and plasma antioxidant activity in diabetes mellitus type I]

Presse Med (FRANCE) Feb 10 1996, 25 (5) p188-92

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 I diabetes.



Oxidative protein damage in human diabetic eye: Evidence of a retinal participation

European Journal of Clinical Investigation (United Kingdom), 1997, 27/2 (141-147)

Considerable evidence indicates that the maintenance of protein redox status is of fundamental importance for cell function, whereas structural changes in proteins are considered to be among the molecular mechanisms leading to diabetic complications. In this study, protein redox status and antioxidant activity were investigated in the lens and vitreous of diabetic and nondiabetic subjects. A significantly lower content of sulphydryl proteins was found in lens and vitreous of diabetic patiel subjects. Moreover, an increased formation of protein-bound free sulphydryls and carbonyl proteins, indices of oxidative damage to proteins, was noted in diabetic patients. All these parameters were shown to be altered particularly when diabetes was complicated with retinal alterations. In addition, glutathione peroxidase activity and ascorbic acid levels, known to exert important antioxidant functions in the eye compartment, were found to be significantly decreased in the lens of diabetic patients, especially in the presence of retinal damage. This study indicates an alteration of protein redox status in subjects affected by diabetes mellitus; lens and vitreous proteins were found to be oxidized to a greater extent in the presence of retinal disease, together with a marked decrease of eye antioxidant systems. These results suggest that oxidative events are involved in the onset of diabetic eye complications, in which the decrease in free radical scavengers was shown to be associated with the oxidation of vitreous and lens proteins. Protein oxidation may, therefore, represent an important mechanism in the onset of eye complications in diabetic patients.

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