Whole Body Health Sale


Heavy Metal Toxicity



Significant mercury deposits in internal organs following the removal of dental amalgam, & development of pre-cancer on the gingiva and the sides of the tongue and their represented organs as a result of inadvertent exposure to strong curing light (used to solidify synthetic dental filling material) & effective treatment: a clinical case report, along with organ representation areas for each tooth.

Omura Y, Shimotsuura Y, Fukuoka A, Fukuoka H, Nomoto T. Heart Disease Research Foundation, New York, NY, U.S.A. Acupunct Electrother Res 1996 Apr-Jun;21(2):133-60

Because of the reduced effectiveness of antibiotics against bacteria (e.g., Chlamydia trachomatis, alpha-Streptococcus, Borrelia burgdorferi, etc.) and viruses (e.g., Herpes Family Viruses) in the presence of mercury, as well as the fact that the 1st author has found that mercury exists in cancer and pre-cancer cell nuclei, the presence of dental amalgam (which contains about 50% mercury) in the human mouth is considered to be a potential hazard for the individual's health. In order to solve this problem, 3 amalgam fillings were removed from the teeth of the subject of this case study. In order to fill the newly created empty spaces in the teeth where the amalgams had formerly existed, a synthetic dental-filling substance was introduced and to solidify the synthetic substance, curing light (wavelength range reportedly between 400-520 nm) was radiated onto the substance in order to accelerate the solidifying process by photo-polymerization. In spite of considerable care not to inhale mercury vapor or swallow minute particles of dental amalgam during the process of removing it by drilling, mercury entered the body of the subject. Precautions such as the use of a rubber dam and strong air suction, as well as frequent water suctioning and washing of the mouth were insufficient. Significant deposits of mercury, previously non-existent, were found in the lungs, kidneys, endocrine organs, liver, and heart with abnormal low-voltage ECGs (similar to those recorded 1-3 weeks after i.v. injection of radioisotope Thallium-201 for Cardiac SPECT) in all the limb leads and V1 (but almost normal ECGs in the precordial leads V2-V6) the day after the procedures were performed. Enhanced mercury evaporation by increased temperature and microscopic amalgam particles created by drilling may have contributed to mercury entering the lungs and G.I. system and then the blood circulation, creating abnormal deposits of mercury in the organs named above. Such mercury contamination may then contribute to intractable infections or pre-cancer. However, these mercury deposits, which commonly occur in such cases, were successfully eliminated by the oral intake of 100 mg tablet of Chinese parsley (Cilantro) 4 times a day (for average weight adults) with a number of drug-uptake enhancement methods developed by the 1st author, including different stimulation methods on the accurate organ representation areas of the hands (which have been mapped using the Bi-Digital O-Ring Test), without injections of chelating agents. Ingestion of Chinese parsley, accompanied by drug-uptake enhancement methods, was initiated before the amalgam removal procedure and continued for about 2 to 3 weeks afterwards, and ECGs became almost normal. During the use of strong bluish curing light to create a photo-polymerization reaction to solidify the synthetic filling material, the adjacent gingiva and the side of the tongue were inadvertently exposed. This exposure to the strong bluish light was found to produce pre-cancerous conditions in the gingiva, the exposed areas of the tongue, as well as in the corresponding organs represented on those areas of the tongue, and abnormally increased enzyme levels in the liver. These abnormalities were also successfully reversed by the oral intake of a mixture of EPA with DHA and Chinese parsley, augmented by one of the non-invasive drug-uptake enhancement methods previously described by the 1st author, repeated 4 times each day for 2 weeks.

Symptomatic treatment of brain tumor patients with sodium selenite, oxygen, and other supportive measures.

Pakdaman A. Klinik fur komplimentare Onkologie und Immuntherapie im Gesundheitspark Beelitz, Beelitz-Heilstatten, Germany.

Biol Trace Elem Res 1998 Apr-May;62(1-2):1-6

Patients (16 women and 16 men) with brain tumors previously treated conservatively by surgery, radiation, and/or chemotherapy with typical symptoms of increased intracranial pressure were consecutively enrolled to test the effects of pharmacological dosages of sodium selenite (selenase) in conjunction with other supportive therapies (biological response modifiers, detoxification, chemotherapy, immunotherapy, oxygen therapy). The rationale for the use of sodium selenite was that the whole-blood selenium levels were subnormal in 70% of the patients on admission. Patients also frequently presented abnormal levels of other minerals, especially lowered sodium and elevated potassium levels, which appears to be characteristic of brain tumor patients. Sodium selenite was administered by infusion at dosages of 1000 microg Se in physiological saline/d for 4-8 wk. In 76% of the patients, a definite, and in 24% a slight improvement of the general condition and a decrease in symptoms, such as nausea, emesis, headache, vertigo, unsteady gait, speech disorders, and Jacksonian seizures, were observed. In all treated patients, improvements of erythrocyte, hemoglobin, and thrombocyte counts were observed. Additional beneficial effects were noted in the patients receiving the oxygen therapy. It is concluded that the sodium selenite can be employed with oxygen therapy and other supportive measures in the management of brain tumor patients.

S-adenosyl-L-methionine a counter to lead intoxication?

Paredes SR, Kozicki PA, Batlle AM.

Comp Biochem Physiol B 1985;82(4):751-7

The effect of S-adenosyl-L-methionine (SAM) administration to both acute and chronic lead exposed mice was investigated. SAM was given s.c. at different doses and for different time intervals. The best results were obtained using 20 mg SAM/kg applied daily over a period of 20-22 days. Results obtained in both acute and chronic lead poisoning were quite similar. GSH concentration in blood and liver, reduced in intoxicated animals was increased after SAM administration reaching normal values. Blood, liver and kidney lead content notably increased at the beginning of SAM treatment and decreased rapidly in the group receiving SAM, attaining values near control levels in 2 weeks. A significant recovery of blood, liver, kidney, spleen and brain delta-aminolevulic acid dehydratase (ALA-D) initially reduced in poisoned animals, was clearly produced after SAM administration. A clear and direct correlation between the recovery of both ALA-D activity and GSH levels and the decreased concentration of lead in tissues was observed, reinforcing our proposal that enhancement of thiol content as a result of SAM administration would facilitate the detoxification process and lead removal, consequently reversing the inactivation of the enzyme. We conclude that SAM therapy is beneficial in the treatment of lead intoxication.

Prevention by rutin of gastric lesions induced by ethanol in rats: role of endogenous prostaglandins.

Perez Guerrero C, Martin MJ, Marhuenda E. Departamento de Farmacia y Tecnologia Farmaceutica, Laboratorio de Farmacodinamia, Facultad de Farmacia, Universidad de Sevilla, Spain.

Gen Pharmacol 1994 May;25(3):575-80

1. This study was designed to demonstrate the cytoprotective effect of Rutin against ethanol-induced gastric injury in rats and to determine whether this cytoprotective effect is mediated by endogenous prostaglandins. 100 and 200 mg/kg of Rutin given orally 1 hr before administration of 1 ml of 100% ethanol significantly (p < 0.01) reduced the area of macroscopic lesions induced by ethanol (84.16 +/- 23.01 and 54.75 +/- 16.05 respectively) when compared to distilled water (305.60 +/- 67.20). However, it did not induce changes in the amount and total proteins and hexosamines content of gastric mucus. 2. Pretreatment with indomethacin, 10 mg/kg s.c. 30 min before Rutin administration, slightly but not significantly reduced the cytoprotective effect. 3. The levels of PGE2 present in the mucous material were not significantly modified with administration of Rutin (100 mg/kg). 4. These results show that Rutin has a cytoprotective effect against ethanol injury in the rat, but this property does not appear to be mediated by endogenous prostaglandins.

Antioxidant activity of silybin in vivo during long-term iron overload in rats.

Pietrangelo A, Borella F, Casalgrandi G, Montosi G, Ceccarelli D, Gallesi D, Giovannini F, Gasparetto A, Masini A. Dipartimento di Medicina Interna, University of Modena, Italy.

Gastroenterology 1995 Dec;109(6):1941-9

BACKGROUND & AIMS: Hepatic iron toxicity may be mediated by free radical species and lipid peroxidation of biological membranes. The antioxidant property of silybin, a main constituent of natural flavonoids, was investigated in vivo during experimental iron overload. METHODS: Rats were fed a 2.5% carbonyl-iron diet and 100 mg.kg body wt-1.day-1 silybin for 4 months and were assayed for accumulation of hepatic lipid peroxidation by-products by immunocytochemistry, mitochondrial energy-dependent functions, and mitochondrial malondialdehyde content. RESULTS: Iron overload caused a dramatic accumulation of malondialdehyde-protein adducts into iron-filled periportal hepatocytes that was decreased appreciably by silybin treatment. The same beneficial effect of silybin was found on the iron-induced accumulation of malondialdehyde in mitochondria. As to the liver functional efficiency, mitochondrial energy wasting and tissue adenosine triphosphate depletion induced by iron overload were successfully counteracted by silybin. CONCLUSIONS: Oral administration of silybin protects against iron-induced hepatic toxicity in vivo. This effect seems to be caused by the prominent antioxidant activity of this compound.

Antioxidant therapy in the prevention of organ dysfunction syndrome and infectious complications after trauma: early results of a prospective randomized study.

Porter JM, Ivatury RR, Azimuddin K, Swami R. The Lincoln Medical Center, Bronx, New York, U.S.A.

Am Surg 1999 May;65(5):478-83; erratum, Am Surg 1999 Sep;65(9):902

Reactive oxygen species have been implicated in the etiology of multiorgan dysfunction syndrome and infectious complications in trauma patients by either direct cellular toxicity and/or the activation of intracellular signaling pathways. Studies have shown that the antioxidant defenses of the body are decreased in trauma patients; these include glutathione, for which N-acetylcysteine is a precursor, and selenium, which is a cofactor for glutathione. Eighteen trauma patients were prospectively randomized to a control or antioxidant group where they received N-acetylcysteine, selenium, and vitamins C and E for 7 days. As compared with the controls, the antioxidant group showed fewer infectious complications (8 versus 18) and fewer organs dysfunctioning (0 versus 9). There were no deaths in either group. We conclude that these preliminary data may support a role for the use of this antioxidant mixture to decrease the incidence of multiorgan dysfunction syndrome and infectious complications in the severely injured patient. This remains to be confirmed in larger trials.

MSM: the multi-purpose compound.

Prater G. Life Extension Magazine 1999 Sep;5(9):71-2 (http://www.lef.org/magazine/mag99/sep99-products.htm) Life Extension Foundation, Ft. Lauderdale, FL. U.S.A.

No abstract available.

Vitamin E and heart disease: basic science to clinical intervention trials.

Pryor WA. The Biodynamics Institute, Louisiana State University, Baton Rouge, LA 70803, U.S.A. wpryor@LSU.edu

Free Radic Biol Med 2000 Jan 1;28(1):141-64

A review is presented of studies on the effects of vitamin E on heart disease, studies encompassing basic science, animal studies, epidemiological and observational studies, and four intervention trials. The in vitro, cellular, and animal studies, which are impressive both in quantity and quality, leave no doubt that vitamin E, the most important fat-soluble antioxidant, protects animals against a variety of types of oxidative stress. The hypothesis that links vitamin E to the prevention of cardiovascular disease (CVD) postulates that the oxidation of unsaturated lipids in the low-density lipoprotein (LDL) particle initiates a complex sequence of events that leads to the development of atherosclerotic plaque. This hypothesis is supported by numerous studies in vitro, in animals, and in humans. There is some evidence that the ex vivo oxidizability of a subject's LDL is predictive of future heart events. This background in basic science and observational studies, coupled with the safety of vitamin E, led to the initiation of clinical intervention trials. The three trials that have been reported in detail are, on balance, supportive of the proposal that supplemental vitamin E can reduce the risk for heart disease, and the fourth trial, which has just been reported, showed small, but not statistically significant, benefits. Subgroup analyses of cohorts from the older three trials, as well as evidence from smaller trials, indicate that vitamin E provides protection against a number of medical conditions, including some that are indicative of atherosclerosis (such as intermittent claudication). Vitamin E supplementation also produces an improvement in the immune system and protection against diseases other than cardiovascular disease (such as prostate cancer). Vitamin E at the supplemental levels being used in the current trials, 100 to 800 IU/d, is safe, and there is little likelihood that increased risk will be found for those taking supplements. About one half of American cardiologists take supplemental vitamin E, about the same number as take aspirin. In fact, one study suggests that aspirin plus vitamin E is more effective than aspirin alone. There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition for which vitamin E provides benefit will have a unique dose-effect curve. Furthermore, different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients. It will be extremely difficult to do trials that adequately probe the dose-effect curve for vitamin E for each condition that it might affect, or to do studies of all the possible combinations of other micronutrients that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time when the science is "complete." At some point, the weight of the scientific evidence must be judged adequate; although some may regard it as early to that judgement now, clearly we are very close. In view of the very low risk of reasonable supplementation with vitamin E, and the difficulty in obtaining more than about 30 IU/day from a balanced diet, some supplementation appears prudent now.

Cysteine metabolism and metal toxicity.

Quig D. Doctor's Data, Inc., West Chicago, IL, U.S.A. dquig@doctorsdata.com

Altern Med Rev 1998 Aug;3(4):262-70

Chronic, low level exposure to toxic metals is an increasing global problem. The symptoms associated with the slow accumulation of toxic metals are multiple and rather nondescript, and overt expression of toxic effects may not appear until later in life. The sulfhydryl-reactive metals (mercury, cadmium, lead, arsenic) are particularly insidious and can affect a vast array of biochemical and nutritional processes. The primary mechanisms by which the sulfhydryl-reactive metals elicit their toxic effects are summarized. The pro-oxidative effects of the metals are compounded by the fact that the metals also inhibit antioxidative enzymes and deplete intracellular glutathione. The metals also have the potential to disrupt the metabolism and biological activities of many proteins due to their high affinity for free sulfhydryl groups. Cysteine has a pivotal role in inducible, endogenous detoxication mechanisms in the body, and metal exposure taxes cysteine status. The protective effects of glutathione and the metallothioneins are discussed in detail. Basic research pertaining to the transport of toxic metals into the brain is summarized, and a case is made for the use of hydrolyzed whey protein to support metal detoxification and neurological function. Metal exposure also affects essential element status, which can further decrease antioxidation and detoxification processes. Early detection and treatment of metal burden is important for successful detoxification, and optimization of nutritional status is paramount to the prevention and treatment of metal toxicity.

The effects of glutathione depletion on reproductive success in oysters, Crassostrea virginica.

Ringwood AH, Conners DE. Marine Resources Research Institute, 217 Fort Johnson Road, Charleston, SC 29412, U.S.A. ringwooda@mrd.dnr.state.sc.us

Mar Environ Res 2000 Jul-Dec;50(1-5):207-11

Glutathione (GSH) is a ubiquitous tripeptide that functions as a very important modulator of cellular homeostasis, including detoxification of metals and oxyradicals. Therefore, depletion of GSH may predispose organisms to pollutant stress. Reproductively active oysters (Crassostrea virginica) were exposed to buthionine sulfoximine in the laboratory to deplete gonadal GSH. The effects of metal exposures (Cd and Cu) on fertilization and developmental assays were evaluated using gametes from control and GSH-depleted adults. Fertilization success was not affected by GSH status, i.e. the fertilization rates of gametes derived from GSH-depleted adults were the same or slightly higher. However, GSH depletion did increase the susceptibility of developing embryos to metal toxicity, i.e. adverse effects on embryonic development were observed at lower metal concentrations with gametes derived from GSH-depleted adults. These effects may be related to diminished removal of free radicals or increased availability of metals. Whereas sperm penetration of embryonic membranes and fertilization success may be facilitated by free radicals, the persistence of free radicals during subsequent developmental periods may adversely affect differentiation and normal development. GSH probably also plays an important role in scavenging toxic metals and reducing metal interactions with essential developmental processes. These results suggest that parental depletion of GSH may increase the susceptibility of embryos to metal toxicity.

Metal toxicity in children.

Roberts JR. June 1999 Training Manual on Pediatric Environmental Health: Putting It into Practice. (http://www.cehn.org/cehn/trainingmanual/pdf/manual-full.pdf) Children's Environmental Health Network, Emeryville, CA, U.S.A.

No abstract available.

Long-term use of nicotine chewing gum and mercury exposure from dental amalgam fillings.

Sallsten G, Thoren J, Barregard L, Schutz A, Skarping G. Department of Occupational Medicine, Sahlgrenska University Hospital, Goteborg, Sweden.

J Dent Res 1996 Jan;75(1):594-8

In experimental studies, chewing gum has been shown to increase the release rate of mercury vapor from dental amalgam fillings. The aim of the present study was to investigate the influence of long-term frequent chewing on mercury levels in plasma and urine. Mercury levels in plasma (P-Hg) and urine (U-Hg), and urinary cotinine were examined in 18 subjects who regularly used nicotine chewing gum, and in 19 referents. Age and number of amalgam surfaces were similar in the two groups. Total mercury concentrations in plasma and urine were determined by means of cold vapor atomic absorption spectrometry. Urinary cotinine was determined by gas chromatography-mass spectrometry. The chewers had been using 10 (median) pieces of gum per day for the past 27 (median) months. P-Hg and U-Hg levels were significantly higher in the chewers (27 nmol/L and 6.5 nmol/mmol creatinine) than in the referents (4.9 nmol/L and 1.2 nmol/mmol creatinine). In both groups, significant correlations were found between P-Hg or U-Hg on the one hand and the number of amalgam surfaces on the other. In the chewers, no correlations were found between P-Hg or U-Hg and chewing time per day or cotinine in urine. Cotinine in urine increased with the number of pieces of chewing gum used. The impact of excessive chewing on mercury levels was considerable.

Alzheimer's disease, dental amalgam and mercury.

Saxe SR, Wekstein MW, Kryscio RJ, Henry RG, Cornett CR, Snowdon DA, Grant FT, Schmitt FA, Donegan SJ, Wekstein DR, Ehmann WD, Markesbery WR. Geriatric Oral Health Program, College of Dentistry, University of Kentucky, Lexington, KY, U.S.A.

J Am Dent Assoc 1999 Feb;130(2):191-9

BACKGROUND: Mercury, or Hg, is a neurotoxin that has been speculated to play a role in the pathogenesis of Alzheimer's disease, or AD. Dental amalgam releases low levels of Hg vapor and is a potential source of Hg for a large segment of the adult population. METHODS: The authors studied 68 subjects with AD and 33 control subjects without AD to determine Hg levels in multiple brain regions at autopsy and to ascertain the subjects' dental amalgam status and history. The subjects were from central Kentucky and Elm Grove, Wis. The authors conducted dental amalgam assessments during the lives of the majority of subjects and in some subjects at the time of autopsy only. The authors also determined three dental amalgam index scores--Event (placement, repair or removal of amalgam), Location and Time In Mouth--in addition to the numbers of and surface area of occlusal amalgam restorations. The authors determined Hg levels in multiple brain regions and performed full neuropathologic evaluations to confirm the normal status of the brain or the presence of AD. RESULTS: The authors found no significant association of AD with the number, surface area or history of having dental amalgam restorations. They also found no statistically significant differences in brain Hg level between subjects with AD and control subjects. CONCLUSIONS: Hg in dental amalgam restorations does not appear to be a neurotoxic factor in the pathogenesis of AD. The authors found that brain Hg levels are not associated with dental amalgam, either from existing amalgam restorations or according to subjects' dental amalgam restoration history. CLINICAL IMPLICATIONS: Dental amalgam restorations, regardless of number, occlusal surface area or time, do not relate to brain Hg levels.

Effect of selenium on the side effect profile of adjuvant chemotherapy/radiotherapy in patients with breast carcinoma. Design for a clinical study.] [Article in German]

Schumacher K.

Med Klin 1999 Oct 15;94 Suppl 3:45-8

Selenium is a very important component of the antioxidative protective mechanism which belongs to every cell. By chemotherapy and radiotherapy a strong increase of free oxygen radicals is induced leading to damage also of normal tissue. This phenomenon is registered as adverse drug reactions. Since, in addition, tumor patients frequently have low selenium blood levels the application of higher doses of selenium in connection with chemo- and radiotherapy will induce the toxicity of the treatment without lowering the efficiency. Within the presented prospective randomized placebo-controlled double-blind phase-III study we intend to answer the question whether the application of higher doses of sodium selenite will reduce the toxicity of chemotherapy and radiotherapy. Primary targets of the study are therefore the evaluation of toxicity according to CTC-criteria and of life quality.

Dependence of cadmium-metallothionein nephrotoxicity on glutathione.

Shaikh ZA, Northup JB, Vestergaard P. Department of Biomedical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881-0809, U.S.A. ZShaikh@uri.edu

J Toxicol Environ Health A 1999 Jun 11;57(3):211-22

Acute cadmium-metallothionein (CdMT) injection is frequently used as a model to study the mechanism of chronic Cd-induced nephrotoxicity. The purpose of this study was to investigate the relationship between glutathione (GSH) status and the ability of CdMT, either administered as a bolus dose or infused over a 24-h period by an osmotic minipump, to cause nephrotoxicity. GSH levels were modulated by pretreatment with either buthionine sulfoximine (BSO) or GSH. BSO enhanced while GSH suppressed acute CdMT nephrotoxicity. An infused dose of CdMT (150 microg Cd/kg) that was well tolerated when delivered over a 24-h period became nephrotoxic when GSH synthesis was inhibited by BSO. With depletion of GSH, as little as 0.4 microg Cd/g renal cortex was sufficient to cause nephrotoxicity after an acute dose of CdMT. While BSO had no effect on renal Cd accumulation, pretreatment with GSH reduced renal cortical Cd accumulation by 36%. CdMT nephrotoxicity was enhanced by depleting renal GSH, but without increasing renal Cd accumulation, which suggests that intracellular GSH is directly involved in protection against CdMT nephrotoxicity. Reduced Cd accumulation in the renal cortex following GSH pretreatment suggests an additional extracellular mechanism of GSH protection. It is concluded that GSH status is an important determinant of CdMT nephrotoxicity, with low GSH levels enhancing and high GSH levels reducing its toxicity, and that the mechanism appears to involve both intracellular and extracellular sites.

Protection against chronic cadmium toxicity by glycine.

Shaikh ZA, Tang W. Department of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881, U.S.A. zshaikh@uriacc.uri.edu

Toxicology 1999 Feb 15;132(2-3):139-46

A Japanese drug containing glycine, glycyrrhizin, and cysteine (Stronger Neo-Minophagen C) has been reported to protect against chronic cadmium (Cd) toxicity. The present study was conducted to evaluate which of the three constituents of this drug was the main antagonist for Cd toxicity and whether the mechanism of protection involved antioxidant action. Adult female Sprague-Dawley rats were injected sc with 5 micromol CdCl2/kg per day, five times per week, for 15 weeks. Four groups of Cd-injected animals received co-treatments with either 10 mg glycyrrhizin/kg, 100 mg glycine/kg, 5 mg cysteine/kg, or with a mixture of all three compounds, five times per week, starting from week 7. An additional Cd-injected group was co-treated with vitamin E (100 mg/kg, five times per week, starting from week 7) as a positive control. Only those animals that received vitamin E, Minophagen mixture, or glycine were protected against Cd-induced hepatotoxicity as well as nephrotoxicity. All three co-treatments suppressed Cd-induced hepatic and renal lipid peroxidation. We conclude that the reported beneficial effects of Stronger Neo-Minophagen C are due to glycine, which appears to protect against chronic Cd toxicity by reducing oxidative stress.

Glutathione status and cadmium neurotoxicity: studies in discrete brain regions of growing rats.

Shukla GS, Srivastava RS, Chandra SV. Industrial Toxicology Research Centre, Lucknow, India.

Fundam Appl Toxicol 1988 Aug;11(2):229-35

Intraperitoneal administration of cadmium (Cd2+, 0.4 mg/kg) daily for 30 days to rats was found to decrease the contents of reduced glutathione (GSH) and increase oxidized glutathione (GSSG) in various brain regions. These changes resulted in a significant decline in the GSH/GSSG ratio in different brain regions, except for the hippocampus and midbrain. In addition, the activities of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (GPDH) were also significantly inhibited in different brain regions. Measurement of regional Cd levels revealed that Cd administration significantly increased the levels in all brain regions except for the hippocampus, which could be the reason for not finding any change in any of the biochemical parameters studied in this region. The observed changes in the regional GSH/GSSG ratios could be the result of inhibition in GR activity, as this enzyme catalyzes an irreversible conversion of GSH to GSSG and is responsible for higher cellular GSH levels. GR uses NADPH in its reaction; therefore, the inhibition of GPDH may further aggravate the situation because of the short supply of NADPH. The alterations in the regional "glutathione status" may affect various related metabolic processes, including those required for detoxification of lipid peroxides which have recently been suggested to play a role in the mechanism of Cd neurotoxicity.

Effect of chronic cadmium exposure on glutathione S-transferase and glutathione peroxidase activities in rhesus monkey: the role of selenium. Sidhu M, Sharma M, Bhatia M, Awasthi YC, Nath R. Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Toxicology 1993 Oct 25;83(1-3):203-13

The effect of cadmium (Cd) on the activity of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) which play an important role in the detoxification of xenobiotics, was studied in the liver, kidney, heart and lung of Rhesus monkeys. Furthermore, the role of selenium (Se) in the modulation of Cd toxicity with respect to GST and GSH-Px was also evaluated. Cadmium exposure (5 mg Cd/kg body wt./day as CdCl2 for 10 weeks) to monkeys resulted in decreased GSH-Px activity in all four organs present in the order liver > kidney > heart > lung. Cadmium administration also resulted in a significant decrease in total GST activity present in the order liver > heart > kidney > lung, whereas a significant increase in the pi class GST activity was observed greatest in the heart followed by lung, kidney and liver. Oral administration of Se (0.5 mg Se/kg body wt./day as Na2SeO3 for 10 weeks) caused a significant increase in GSH-Px activity in the order liver > heart > kidney > lung. Selenium administration caused an increase in total GST activity in liver and lung but a decrease in kidney and heart. Simultaneous administration of Cd and Se resulted in an increase in total GST activity (except in lung) including the pi class activity as well as GSH-Px activity in all four tissues under study. Thus, the mechanism by which selenium decreases Cd toxicity in Rhesus monkeys, seems to rely on the protection of the enzyme systems GST and GSH-Px in the four organs, possibly by forming non-toxic cadmium selenide.

Activities of silymarin and its flavonolignans upon low density lipoprotein oxidizability in vitro.

Skottova N, Krecman V, Simanek V. Institute of Medical Chemistry, Medical Faculty, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic.

Phytother Res 1999 Sep;13(6):535-7

Silymarin, a standardized extract from Silybum marianum, inhibited in vitro the copper- nduced oxidation of human LDL in a concentration-dependent manner. Silybin, a main flavonolignan of silymarin, appeared to be responsible for this LDL antioxidant effect. Silychristin and silydianin, other flavonolignans of silymarin, acted rather as pro- oxidants, but with regard to their content in silymarin, it did not contribute significantly to the reduction of the total LDL antioxidant capacity of silymarin. Copyright 1999 John Wiley & Sons, Ltd.

Case report of metallic mercury injury.

Smith SR, Jaffe DM, Skinner MA. Department of Pediatric Emergency Medicine, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO 63110-1077, U.S.A.

Pediatr Emerg Care 1997 Apr;13(2):114-6

OBJECTIVE: Injury and poisoning from metallic mercury has become a rare event. Review of the literature and a case report of pediatric metallic mercury injury are presented. DESIGN: A case report. SETTING: The Emergency Department at St. Louis Children's Hospital. PATIENTS OR PARTICIPANTS: A 15-year-old boy. INTERVENTIONS: None. MAIN OUTCOME MEASURES: None. RESULTS: The 15-year-old boy fell on a broken mercury thermometer. A subcutaneous abscess formed on his left forearm during the next five days. He had no signs or symptoms of mercury toxicity. His wound was debrided in the operating room and healed completely after several months. CONCLUSIONS: This case shows elemental mercury from a thermometer as a potential, if unusual, source of mercury toxicity.

Carcinogen binding to various types of dietary fiber.

Smith-Barbaro P, Hanson D, Reddy BS.

J Natl Cancer Inst 1981 Aug;67(2):495-7

The percent of the carcinogen 1,2-dimethylhydrazine (DMH) bound to a variety of fibers, such as wheat bran, corn bran, citrus pulp, citrus pectin, and alfalfa, was examined at pH values ranging from 1 to 12. The percent of DMH bound to wheat bran increased from 4% at PH 1 to 55% at pH 2 to 77% at pH 12. A sharp rise in carcinogen binding to corn bran occurred between pH 5% of the DMH was bound and pH 8 where 51% of the DMH was bound. The percent of DMH bound to dehydrated citrus pulp also increased as the pH increased with 10% binding observed at pH 1 and with 57% binding observed at pH 12. Between pH 2 and pH 7, the percent of DMH bound to pectin decreased from 60 to 11%. As the pH became more basic, the percent of DMH bound to pectin increased to 42% at pH 12. The sharpest rise in the percent of DMH bound to alfalfa meal occurred between pH 10.5 and pH 12.0. Results from this experiment showed that the affinity to various types of dietary fibers for the colon carcinogen DMH was differentially affected by pH. These results suggested that the protective effect of certain types of dietary fiber against chemically induced colon cancer my in part be attributed to enhanced carcinogen binding by dietary fiber in the colon.

Stimulatory effect of Silibinin on the DNA synthesis in partially hepatectomized rat livers: non-response in hepatoma and other malign cell lines.

Sonnenbichler J, Goldberg M, Hane L, Madubunyi I, Vogl S, Zetl I.

Biochem Pharmacol 1986 Feb 1;35(3):538-41

No abstract available.

Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells.

Sonnenbichler J, Scalera F, Sonnenbichler I, Weyhenmeyer R. Max Planck Institute for Biochemistry, Martinsried, Germany.

J Pharmacol Exp Ther 1999 Sep;290(3):1375-83

The biochemical influence of flavonolignans from the milk thistle Silybum marianum has been tested on kidney cells of African green monkeys. Two nonmalignant cell lines were selected, with the focus of the work on the fibroblast-like Vero line. Proliferation rate, biosynthesis of protein and DNA, and the activity of the enzyme lactate dehydrogenase (as a measure of the cellular metabolic activity) were chosen as parameters for the effect of the flavonolignans. Silibinin and silicristin show remarkable stimulatory effects on these parameters, mainly in Vero cells; however, isosilibinin and silidianin proved to be inactive. In vitro experiments with kidney cells damaged by paracetamol, cisplatin, and vincristin demonstrated that administration of silibinin before or after the chemical-induced injury can lessen or avoid the nephrotoxic effects. The results warrant in vivo evaluations of the flavonolignan derivatives.

[Evaluation of the antiradical protector effect of multifermented milk serum with reiterated dosage in rats.] [Article in French]

Stella V, Postaire E. Direction Scientifique, Pharmacie Centrale des Hopitaux, Paris.

C R Seances Soc Biol Fil 1995;189(6):1191-7

Epidemiological and experimental studies suggest that dietary milk products may exert an inhibitory effect on the development of several types of tumors. Some recent experiments in rodents indicate that the antitumor activity of the dairy product is in the protein fraction and more specifically in the whey protein component of milk. It has been demonstrated that whey protein diets result in increased glutathione (GSH) concentration in a number of tissues, and that some of the beneficial effects of whey protein intake are abrogated by inhibition of GSH synthesis. Whey protein is particularly rich in substrates for GSH synthesis. It has been suggested that whey protein may be exerting its effect on carcinogenesis and VIH infection by enhancing GSH concentration. Lactoferrin, one of the proteins contained in whey has aise been studied in this way. It has been suggested that lactoferrin binding may play an important role in maintaining, optimal mononuclear phagocyte function, thus protecting adjacent tissue against phagocyte derived radicals. Moreover it has been demonstrated by one of us that the level of plasma lactoferrin were decreased in HIV-1 infected patients in relation to the progression of the disease. The aim of the present study is to evaluate in rat the reactive oxygen species, scavenger activities (ROSSA) of red blood cells (RBCs) with a multifermented whey (SK 344), by repeated doses during 16 days. This study has permitted to demonstrate in vivo that the SK 344 has an excellent ROSSA corresponding to a limitation of the lipoperoxidation of RBCs membranes by singlet oxygen and nitric oxide. We can conclude that whey protein, lactoferrin and multifermented whey are good candidates as dietary inhibitors of the oxidative stress and should be considered as potential medicinal foods in various pathologies as HIV infection and cancer.

Restoration of the cellular thiol status of peritoneal macrophages from CAPD patients by the flavonoids silibinin and silymarin.

Tager M, Dietzmann J, Thiel U, Hinrich Neumann K, Ansorge S. Institute of Immunology, Otto-von-Guericke University, Leipziger Str. 44 D-39120 Magdeburg, Germany. michael.tager@medizin.uni-magdeburg.de

Free Radic Res 2001 Feb;34(2):137-51

During continuous ambulatory peritoneal dialysis (CAPD) the peritoneal immune ells, mainly macrophages, are highly compromised by multiple factors including oxidative stress, resulting in a loss of functional activity. One reason for the increase of inflammatory reactions could be an imbalance in the thiol-disulfide status. Here, the possible protective effects of the antioxidant flavonoid complex silymarin and its major component silibinin on the cellular thiol status were investigated. Peritoneal macrophages from dialysis fluid of 30 CAPD patients were treated with silymarin or silibinin up to 35 days. A time-dependent increase of intracellular thiols was observed with a nearly linear increment up to 2.5-fold after 96 hours, reaching a maximum of 3.5-fold after 20 days of culture. Surface-located thiols were also elevated. The stabilization of the cellular thiol status was followed by an improvement of phagocytosis and the degree of maturation as well as significant changes in the synthesis of IL-6 and IL-1ra. Furthermore, the treatment of peritoneal macrophages with flavonoids in combination with cysteine donors resulted in a shortened and more efficient time course of thiol normalization as well as in a further increased phagocytosis. In addition, GSH-depletion in thiol-deficient media simulating CAPD procedures led to intracellular thiol deficiency similar to the in vivo situation. It is concluded that treatment with milk thistle extracts silymarin and silibinin alone or, more effectively in combination with cysteine donors, provide a benefit for peritoneal macrophages of CAPD-patients due to a normalization and activation of the cellular thiol status followed by a restoration of specific functional capabilities.

Preventive effect of vitamin E in cadmium intoxication.

Tandon SK, Singh S, Dhawan M. Industrial Toxicology Research Centre, Lucknow, India.

Biomed Environ Sci 1992 Mar;5(1):39-45

The influence of vitamin E on cadmium intoxication was investigated in rats. The exposure to cadmium (1 mg/kg, Cd as CdCl2.2H2O, intraperitoneally for 7 days) decreased the activity of hepatic and renal glutamic oxalacetic and glutamic pyruvic transaminases (GOT, GPT) and alkaline phosphatase (ALP) accompanied by increase in the levels of serum GOT and GPT and urinary protein. Simultaneous administration of vitamin E (5 mg/kg, intramuscularly for 7 days) reduced these Cd induced biochemical alterations. The accumulation of Cd in blood, liver and kidney also decreased significantly upon co-exposure to vitamin E. The antioxidant property of vitamin E seems to be responsible for the observed protection of Cd intoxication. Nephrotoxicity of cadmium-metallothionein: protection by zinc and role of glutathione.

Tang W, Sadovic S, Shaikh ZA. College of Pharmacy, University of Rhode Island, Kingston, RI 02881, U.S.A.

Toxicol Appl Pharmacol 1998 Aug;151(2):276-82

Chronic cadmium (Cd) exposure can cause renal proximal tubular dysfunction resulting from the release of Cd metallothionein (CdMT) from the liver and its accumulation and degradation in the renal tubular epithelial cells. Pretreatment with zinc (Zn) can protect against acute CdMT nephrotoxicity. While induction of MT by Zn plays a part in Zn protection, other factors, such as glutathione (GSH), may also be involved because protection is offered even in MT-null mice. The present study was designed to investigate the involvement of GSH in Zn protection against acute CdMT nephrotoxicity. The study was carried out in MT-null mice to remove the induction of MT by Zn as a confounding variable. Three approaches were used to modulate renal cortex GSH levels: buthionine sulfoximine (BSO) was administered to inhibit GSH synthesis, and GSH and Zn were administered to increase the GSH levels. Both GSH and Zn were effective in protecting against CdMT nephrotoxicity. Elevation in renal cortex GSH levels, however, was not essential for Zn protection, as a low dose of Zn that caused no significant increase in renal GSH also protected against CdMT. On the other hand, maintenance of normal GSH status was essential for Zn protection, as inhibition of GSH synthesis abolished this protection. Both GSH and Zn reduced the accumulation of Cd as well as MT in the renal cortex, with Zn causing greater reduction in Cd accumulation than that of MT. The relative intracellular distribution of Cd was unaltered. These results suggest that in MT-null mice Zn protects against CdMT nephrotoxicity by possibly displacing some of the Cd from CdMT as well as reducing the uptake of CdMT, and that this protection requires the maintenance of normal GSH status. Copyright 1998 Academic Press.

Association of glutathione S-transferase isozyme-specific induction and lipid peroxidation in two inbred strains of mice subjected to chronic dietary iron overload.

Tjalkens RB, Valerio LG Jr, Awasthi YC, Petersen DR. Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80262, U.S.A.

Toxicol Appl Pharmacol 1998 Jul;151(1):174-81

The alpha-class glutathione S-transferases are proposed to play a prominent role in catalyzing the conjugation of glutathione with electrophilic aldehydic products of lipid peroxidation. The effect of iron-induced lipid peroxidation on induction of glutathione S-transferase (GST) isozymes A1 and A4 in the livers of male C57/BL6Ibg and DBA/J2Ibg mice was studied. C57 and DBA mice were fed for 4 months on a diet supplemented with iron as ferrocene and then were assessed for liver injury, hepatic iron loading, indices of lipid peroxidation, GST activity, and induction of GST isozymes A1 and A4. Iron-treated animals displayed a loss in body weight from pair-fed controls and had large increases in hepatic non-heme iron with concomitant liver injury, as measured by serum alanine aminotransferase. Hepatic lipid hydroperoxides, a direct measure of oxidized membrane lipids, were significantly increased only in C57 mice, but hepatic concentrations of reduced glutathione (GSH) were significantly increased in both inbred strains. Total GST activity toward 1-chloro-2,4-dinitrobenzene was significantly increased in C57 mice but not in DBA. Western blot studies using polyclonal antibodies specific for GST A1 and A4 revealed significant increases of 1.5-2.0-fold in these GST isoforms in both inbred strains. These results in a unique murine model for hepatic iron overload further support recent in vivo studies (Khan et al., Toxicol. Appl. Pharmacol., 131, 63-72, 1995) that have associated induction of GST A4 with protection against oxidative stress-induced lipid peroxidation. The observed increases in lipid hydroperoxides, hepatic GSH, GST activity, and GST A1 and A4 protein strongly support the hypothesis that induction of GST A1 and A4 represents an important protective event in the detoxification of electrophilic products of lipid peroxidation. Copyright 1998 Academic Press.

ToxFAQs™ for Aluminum. CAS 7429-90-5.

Agency for Toxic Substances and Disease Registry. June 1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop E-29, Atlanta, GA 30333, U.S.A.

HIGHLIGHTS: Everyone is exposed to low levels of aluminum from food, air, and water. Exposure to high levels of aluminum may result in respiratory problems. Aluminum has been found in at least 427 of the 1,467 National Priorities List sites identified by the Environmental Protection Agency (EPA).

ToxFAQs™ for Arsenic. CAS 7440-38-2.

Agency for Toxic Substances and Disease Registry. July 2001 Division of Toxicology, 1600 Clifton Road NE, Mailstop E-29, Atlanta, GA 30333, U.S.A.

HIGHLIGHTS: Exposure to higher than average levels of arsenic occurs mostly in the workplace, near hazardous waste sites, or in areas with high natural levels. At high levels, inorganic arsenic can cause death. Exposure to lower levels for a long time can cause a discoloration of the skin and the appearance of small corns or warts. Arsenic has been found at 1,014 of the 1,598 National Priority List sites identified by the Environmental Protection Agency (EPA).

ToxFAQs™ for Cadmium. CAS 7440-43-9.

Agency for Toxic Substances and Disease Registry. June 1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop E-29, Atlanta, GA 30333, U.S.A.

HIGHLIGHTS: Exposure to cadmium happens mostly in the workplace where cadmium products are made. The general population is exposed from breathing cigarette smoke or eating cadmium contaminated foods. Cadmium damages the lungs, can cause kidney disease, and may irritate the digestive tract. This substance has been found in at least 776 of the 1,467 National Priorities List sites identified by the Environmental Protection Agency (EPA).

ToxFAQs™ for Lead. CAS 7439-92-1.

Agency for Toxic Substances and Disease Registry. June 1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop E-29, Atlanta, GA 30333, U.S.A.

HIGHLIGHTS: Exposure to lead can happen from breathing workplace air or dust, eating contaminated foods, or drinking contaminated water. Children can be exposed from eating lead-based paint chips or playing in contaminated soil. Lead can damage the nervous system, kidneys, and reproductive system. Lead has been found in at least 1,026 of 1,467 National Priorities List sites identified by the Environmental Protection Agency (EPA).

ToxFAQs™ for Mercury. CAS 7439-97-6.

Agency for Toxic Substances and Disease Registry. April 1999 Division of Toxicology, 1600 Clifton Road NE, Mailstop E-29, Atlanta, GA 30333, U.S.A.

HIGHLIGHTS: Exposure to mercury occurs from breathing contaminated air, ingesting contaminated water and food, and having dental and medical treatments. Mercury, at high levels, may damage the brain, kidneys, and developing fetus. This chemical has been found in at least 714 of 1,467 National Priorities List sites identified by the Environmental Protection Agency.

Effects of some thiol chelators on enzymatic activities in blood, liver and kidneys of acute arsenic (III) exposed mice.

Tripathi N, Flora SJ. Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India. Biomed Environ Sci 1998 Mar;11(1):38-45

The effects of meso 2, 3-dimercaptosuccinic acid (DMSA), sodium 2, 3-dimercaptopropane 1-sulfonate (DMPS) and S-adenosyl L-methionine (SAM) on the enzymatic activities of mice were studied. The mice were given intraperitoneal (i.p.) injections of these chelating agents (1 mmol/kg) and 3 h later the activity of delta-aminolevulinic acid dehydratase (ALAD) in the blood, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (ALP) in the liver and kidney were determined. The activity of blood ALAD was significantly increased by the administration of DMSA and SAM while DMPS had only a moderate effect. The activities of other hepatic enzymes changed little when the mice were treated with these chelating agents, except for a significant reduction in hepatic ALP activity following DMPS administration. Arsenic (III) administration markedly increased the activities of ALT and ALP in the liver and kidneys. The changes in the enzymatic activities by treatment with arsenic were prevented by injection of DMSA, DMPS and SAM, DMSA being the most effective. These results indicate that DMSA, DMPS and SAM were not toxic to the liver or kidneys of mice and that treatment with DMSA is more effective than DMPS or SAM in protecting mice from acute hepatic or renal toxicity caused by arsenic.

Serum selenium and glutathione-peroxidase activities and their interaction with toxic metals in dialysis and renal transplantation patients.

Turan B, Delilbasi E, Dalay N, Sert S, Afrasyap L, Sayal A. Department of Biophysics, Faculty of Medicine, Ankara University, Turkiye. Biol Trace Elem Res 1992 Apr-Jun;33:95-102

Selenium, aluminum, cadmium, and magnesium concentrations and glutathione-peroxidase activities in sera of 35 healthy individuals, 30 renal transplants, and 30 hemodialysis patients were measured. Serum selenium, aluminum, and cadmium concentrations in both groups of patients were higher than the controls (p less than 0.001), whereas the serum glutathione-peroxidase levels were lower (p less than 0.001). According to our results, it can be concluded that the patients receiving hemodialysis are subjected to more toxic elements than the transplantation patients. These findings imply that dietary selenium supplement may be suggested in renal failure for the detoxification of elements, such as cadmium and mercury. The essential trace element selenium takes part not only in the direct protection of endothelial cells against the accumulation of aggressive oxygen species, but also in the prevention of the toxic effects of cadmium or in the modulation of the active calcium transport.

Deferoxamine (Systemic).

USNLM/NIH (no authors given). 2001 Drug Information (http://www.nlm.nih.gov/medlineplus/druginfo). U.S. National Laboratory of Medicine/National Institutes of Health, Bethesda, MD, U.S.A. (http://www.nlm.nih.gov/medlineplus/druginfo)

No abstract available.

DMSA (Succimer Systemic).

USNLM/NIH (no authors given). 2001 Drug Information (http://www.nlm.nih.gov/medlineplus/druginfo). U.S. National Laboratory of Medicine/National Institutes of Health, Bethesda, MD, U.S.A. (http://www.nlm.nih.gov/medlineplus/druginfo)

No abstract available.

EDTA (Edetate Disodium Systemic).

USNLM/NIH (no authors given). 2001 Drug Information (http://www.nlm.nih.gov/medlineplus/druginfo). U.S. National Laboratory of Medicine/National Institutes of Health, Bethesda, MD, U.S.A. (http://www.nlm.nih.gov/medlineplus/druginfo)

No abstract available.

Penicillamine (Systemic).

USNLM/NIH (no authors given). 2001 Drug Information (http://www.nlm.nih.gov/medlineplus/druginfo). U.S. National Laboratory of Medicine/National Institutes of Health, Bethesda, MD, U.S.A.

Biochemical bases of the pharmacological action of the flavonoid silymarin and of its structural isomer silibinin.

Valenzuela A, Garrido A. Unidad de Bioquimica Farmacologica y Lipidos, Universidad de Chile, Santiago. Biol Res 1994;27(2):105-12

The flavonoid silymarin and one its structural components, silibinin, have been well characterized as hepato-protective substances. However, little is known about the biochemical mechanisms of action of these substances. This review deals with recent investigations to elucidate the molecular action of the flavonoid. Three levels of action have been proposed for silymarin in experimental animals: a) as an antioxidant, by scavenging prooxidant free radicals and by increasing the intracellular concentration of the tripeptide glutathione; b) regulatory action of the cellular membrane permeability and increase of its stability against xenobiotic injury; c) at the nuclear expression, by increasing the synthesis of ribosomal RNA by stimulating DNA polymerase I and by exerting a steroid-like regulatory action on DNA transcription. The specific hepatoprotective action of silibinin against the toxicity of ethanol, phenylhydrazine and acetaminophen is also discussed. It is suggested that the biochemical effects observed for the flavonoid in experimental models may settle the basis for understanding the pharmacological action of silymarin and silibinin.

Induction of lesions of selenium-vitamin E deficiency in ducklings fed silver, copper, cobalt, tellurium, cadmium, or zinc: protection by selenium or vitamin E supplements.

Van Vleet JF, Boon GD, Ferrans VJ. Am J Vet Res 1981 Jul;42(7):1206-17

In 3 experiments, 684 newly hatched White Pekin ducklings were fed (for 15 to 28 days) a commercial starter mash that was adequate in selenium and vitamin E (Se-E) content, either alone or with supplements of Ag (3,000 mg/kg of feed, as acetate), Cu (1,500 mg/kg, as sulfate), Co (200 or 500 mg/kg, as chloride), Te (500 mg/kg, as tetrachloride), Cd (100 or 500 mg/kg, as sulfate), Zn (3,000 or 6,000 mg/kg, as sulfate), or V (100 mg/kg, as vanadate). The ducklings fed Ag, Cu, Co, Te, Cd, and Zn frequently developed lesions characteristic of Se-E deficiency, such as necrosis of skeletal and cardiac muscle and of smooth muscle of the gizzard and intestine. Complete protection from the muscle lesions produced by Cu, Co, Te, Cd, and Zn supplements was provided by vitamin E (200 IU of alpha-tocopherol acetate/kg) and Se (2 mg/kg, as selenite). Ducklings fed Ag were protected by supplements of vitamin E and partial protection was achieved by Se addition. The birds fed excessive Zn developed pancreatic necrosis and fibrosis that was not prevented by supplements of Se or vitamin E. Terminally, blood glutathione peroxidase activity was low and hepatic Se concentration was increased in the ducklings fed Ag. However, neither blood glutathione peroxidase activity nor hepatic Se concentrations were consistently abnormal in ducklings fed other trace elements, although lesions of Se-E deficiency were often present in these animals.

Lead induced disorders in hematopoietic and drug metabolizing enzyme system and their protection by ascorbic acid supplementation.

Vij AG, Satija NK, Flora SJ. Defence Institute of Physiology and Allied Sciences, Timarpur, Delhi, India. Biomed Environ Sci 1998 Mar;11(1):7-14

Effect of vitamin C supplementation in restoring lead induced alterations in hematopoietic system and drug metabolizing enzymes were investigated in male rats. Intraperitoneal administration of 20 mg/kg lead produced a significant inhibition of heme synthesis in blood and liver and drug metabolism in liver. Toxic insult by lead also resulted into a marked decline in tissue thiols and vitamin C levels. Oral supplementation of vitamin C (100 mg/kg for 3 days) completely restored blood delta aminolevulinic acid dehydratase, uroporphyrinogen I synthetase and a few drug metabolizing enzymes. Level of vitamin C and sulfhydryl contents too recovered to a great extent. A marked reduction in blood and liver lead concentration occurred on vitamin C supplementation although renal lead contents were marginally reduced in lead exposed animals. The results, thus, indicate a significant protective action of vitamin C against toxic effects of lead on heme synthesis and drug metabolism.

Vitamin A supplementation: implications for morbidity and mortality in children.

Villamor E, Fawzi WW. Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115, U.S.A. J Infect Dis 2000 Sep;182 Suppl 1:S122-33

Vitamin A deficiency impairs epithelial integrity and systemic immunity and increases the incidence and severity of infections during childhood. However, findings from vitamin A supplementation trials are not consistent. Supplementation has resulted in significant reductions in mortality in several (but not all) large community-based trials among apparently healthy children. In hospital-based studies, vitamin A supplements have been consistently found to reduce the severity of measles infection, but no effect on nonmeasles respiratory infections has been observed. In some cases, the supplements were associated with an apparently increased risk of lower respiratory infection. Vitamin A supplements also reduced the severity of diarrhea in most (but not all) trials. Potential explanations for the differences in efficacy across trials are reviewed. While vitamin A supplementation is effective in reducing total mortality and complications from measles infections, it is likely to be more effective in populations suffering from nutritional deficiencies.

Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings.

Vimy MJ, Takahashi Y, Lorscheider FL. Department of Medicine, Faculty of Medicine, University of Calgary, Alberta, Canada. Am J Physiol 1990 Apr;258(4 Pt 2):R939-45

In humans, the continuous release of Hg vapor from dental amalgam tooth restorations is markedly increased for prolonged periods after chewing. The present study establishes a time-course distribution for amalgam Hg in body tissues of adult and fetal sheep. Under general anesthesia, five pregnant ewes had twelve occlusal amalgam fillings containing radioactive 203Hg placed in teeth at 112 days gestation. Blood, amniotic fluid, feces, and urine specimens were collected at 1- to 3-day intervals for 16 days. From days 16-140 after amalgam placement (16-41 days for fetal lambs), tissue specimens were analyzed for radioactivity, and total Hg concentrations were calculated. Results demonstrate that Hg from dental amalgam will appear in maternal and fetal blood and amniotic fluid within 2 days after placement of amalgam tooth restorations. Excretion of some of this Hg will also commence within 2 days. All tissues examined displayed Hg accumulation. Highest concentrations of Hg from amalgam in the adult occurred in kidney and liver, whereas in the fetus the highest amalgam Hg concentrations appeared in liver and pituitary gland. The placenta progressively concentrated Hg as gestation advanced to term, and milk concentration of amalgam Hg postpartum provides a potential source of Hg exposure to the newborn. It is concluded that accumulation of amalgam Hg progresses in maternal and fetal tissues to a steady state with advancing gestation and is maintained. Dental amalgam usage as a tooth restorative material in pregnant women and children should be reconsidered.

Silymarin: a review of its clinical properties in the management of hepatic disorders.

Wellington K, Jarvis B. Adis International Limited, Auckland, New Zealand. demail@adis.co.nz BioDrugs 2001;15(7):465-89

The mechanisms of action of silymarin involve different biochemical events, such as the stimulation of the synthetic rate of ribosomal RNA (rRNA) species through stimulation of polymerase I and rRNA transcription, protecting the cell membrane from radical-induced damage and blockage of the uptake of toxins such as alpha-amanitin. Studies in patients with liver disease have shown that silymarin increases superoxide dismutase (SOD) activity of lymphocytes and erythrocytes, as well as the expression of SOD in lymphocytes. Silymarin has also been shown to increase patient serum levels of glutathione and glutathione peroxidase. Silybin 20 to 48 mg/kg/day has shown promise as a clinical antidote to acute Amanita (deathcap mushroom) poisoning. Primary efficacy data from 3 trials which examined the therapeutic potential of silymarin in patients with cirrhosis, and included patient survival as an end-point, demonstrated that silymarin had no significant beneficial effect on patient mortality. However, upon subanalysis, silymarin 420 mg/day had a significantly beneficial effect on patient survival rate (compared with patients receiving placebo) in 1 randomised, double-blind trial in patients with alcoholic cirrhosis. Silymarin 420 mg/day was also shown to improve indices of liver function [AST, ALT, gamma-glutamyl transferase and bilirubin] in patients with liver disease of various aetiology, including those exposed to toxic levels of toluene or xylene; however, it was largely ineffective in patients with viral hepatitis. Reports of adverse events while receiving silymarin therapy are rare. However, there have been accounts of nausea, epigastric discomfort, arthralgia, pruritus, headache and urticaria. Silymarin has also been reported to have possibly caused a mild laxative effect. CONCLUSION: The antioxidant properties of silymarin (a mixture of at least 4 closely related flavonolignans, 60 to 70% of which is a mixture of 2 diastereomers of silybin) have been demonstrated in vitro and in animal and human studies. However, studies evaluating relevant health outcomes associated with these properties are lacking. Although silymarin has low oral absorption, oral dosages of 420 mg/day have shown some therapeutic potential, with good tolerability, in the treatment of alcoholic cirrhosis. Moreover, silybin 20 to 48 mg/kg/day has shown promise as an antidote for acute mushroom poisoning by Amanita phalloides; however, further studies paying attention to the amount of ingested mushroom and time elapsed before administration of treatment are needed to clarify its role in this indication. Studies in patients with the early onset of liver disease may demonstrate the liver regeneration properties that silymarin is promoted as possessing.

Chelation therapy: conventional treatments.

Wentz PW. (LabCorp., Burlington, NC). May 2000 Advance Magazines for Administrators of the Laboratory (http://www.advanceforal.com/common/editorial/editorial/aspx). Merion Publications, King of Prussia, PA

Maternal low level lead and pregnancy outcomes.

West WL, Knight EM, Edwards CH, Manning M, Spurlock B, James H, Johnson AA, Oyemade UJ, Cole OJ, Westney OE, et al. Department of Pharmacology, College of Medicine, Howard University, Washington, D.C. 20059.

J Nutr 1994 Jun;124(6 Suppl):981S-986S

We examined the relationship between the concentrations of blood lead and pregnancy outcomes in a subset of 349 African American women who enrolled in the program project, "Nutrition, Other Factors, and the Outcome of Pregnancy." Vitamin-mineral supplement users had significantly higher serum levels of ascorbic acid and vitamin E. Also, in supplement users, there were significantly lower mean concentrations of maternal blood lead. Inverse correlations were found between maternal levels of lead and the antioxidant vitamins, vitamin E and ascorbic acid. In addition, significant Pearson's correlations were observed between maternal blood lead levels and the following variables: positive correlations with calcium, phosphorus, mean corpuscular volume; inverse correlations with gestational age, Ponderal Index, infant orientation, and hematologic values. In the total subset, the three trimester sample means for maternal blood lead concentrations were not significantly different for mothers of infants who weighed less than 2500 g (low birth weight) and those who were delivered infants who weighed 2500 g or more. Clinically, nutrition may play a role in the reduction of potentially adverse effects from lead during pregnancy, i.e. protection of the fetus against lead toxicity and/or free radical damage through the antioxidant actions of vitamin E and ascorbic acid. Even when maternal blood lead levels are within the so-called "safe" range, maternal/use of a vitamin supplement supplying vitamin E and ascorbic acid during pregnancy may offer protection.


WHO (no authors given). 1998 Guidelines for Drinking-Water Quality, Second Edition, Health Criteria and Other Supporting Information, pp. 3-13 (http://www.who.into/water_sanitation_health/GDWQ/Chemicals/aluminfull.html). World Health Organization, Geneva.

No health-based guideline value for aluminium was recommended in the second edition of the WHO Guidelines for drinking-water quality. It was concluded that although further studies were needed, the balance of epidemiological and physiological evidence did not support a causal role for aluminium in Alzheimer disease. An aluminium concentration of 0.2 mg/litre in drinking-water provided a compromise between the practical use of aluminium salts in water treatment and discoloration of distributed water. The Coordinating Committee for the updating of the WHO Guidelines recommended that a health criteria document be prepared for aluminium, based on the IPCS Environmental Health Criteria monograph that was finalized in 1995.

[Mercury concentration in the mouth mucosa of patients with amalgam fillings.] [Article in German]

Willershausen-Zonnchen B, Zimmermann M, Defregger A, Schramel P, Hamm G. Poliklinik fur Zahnerhaltung und Parodontologie, Universitat Munchen. Dtsch Med Wochenschr 1992 Nov 13;117(46):1743-7

Mercury concentrations were measured in specimens of oral mucosa taken during oral surgery from 90 patients (53 men, 37 women, mean age 42 +/- 16 years); 30 of the patients had no amalgam fillings. All the mucosal specimens extended for at least 2-3 mm from the epithelium of the gingival margin and were clinically and radiologically normal. Thirteen patients without metallic fillings of any kind had mercury concentrations of 118.4 +/- 83.7 ng/g tissue, and in 17 patients with precious metal fillings but no amalgam the mean mercury concentrations were 144 +/- 290 ng/g tissue. Seventeen patients with 1-3 amalgam fillings had an average of 1975 +/- 4300 ng/g tissue and in 26 patients with 3-6 amalgam fillings the average concentration was 1158 +/- 2500 ng/g tissue. In 17 patients with more than six amalgam fillings the mean mercury concentration was 2302 +/- 5600 ng/g tissue. Although these results demonstrate a considerable degree of transfer of mercury from the amalgam fillings to the oral mucosa, it had not resulted in any clinically detectable mucosal lesions.

Effects of lead on glutathione S-transferase expression in rat kidney: a dose-response study.

Wright LS, Kornguth SE, Oberley TD, Siegel FL. Waisman Center, University of Wisconsin, Madison, WI 53705, U.S.A. Toxicol Sci 1998 Dec;46(2):254-9

Glutathione S-transferases (GST, EC are a family of phase II detoxification enzymes involved in the conjugation of glutathione to a highly diverse group of compounds. The purpose of this study was to evaluate the dose-response effects of lead acetate administration on the expression of rat kidney GST. Sprague-Dawley rats were injected with doses of lead acetate ranging from 0.11 to 114 mg/kg (0.3 to 300 mumol/kg) for three consecutive days and sacrificed 24 h later. Kidney GST activity, GST isoform HPLC profiles, blood lead analysis, and electron microscopy were performed. A dose of 1.1 mg/kg lead acetate resulted in a blood lead level of 26 micrograms/dl and produced a significant increase in GST activity which continued to increase with dose up to 38 mg/kg. Morphological changes were detected at 3.8 mg/kg and increasing severity of cellular damage paralleled dose, blood lead levels, and changes in body weight. Individual GST isoforms exhibited different thresholds and maxima; rGSTP1 and rGSTM1 had thresholds of 1.1 and 3.8 mg/kg, respectively, very similar rates of increase with dose, and a maximum yield that was 450% above control at a dose of 38 mg/kg for both enzymes. rGSTA1 and rGSTA3 showed similar thresholds (1.1 mg/kg) and maximal fold increase (275%) but varied in the relative response to each dose. These results indicate that renal GST increases occur at lead levels which are environmentally significant, that these changes precede cellular damage, and suggest that GST may serve as a tissue biomarker of lead exposure.

Metabolic methylation is a possible genotoxicity-enhancing process of inorganic arsenics.

Yamanaka K, Hayashi H, Tachikawa M, Kato K, Hasegawa A, Oku N, Okada S. Department of Biochemical Toxicology, Nihon University College of Pharmacy, Chiba, Japan. Mutat Res 1997 Nov 27;394(1-3):95-101

To elucidate if the metabolic methylation participates in the induction of inorganic arsenic-responsible genetic damage, arsenite (ARS) and its methylated metabolites, methanearsonic acid (MMAA) and dimethylarsinic acid (DMAA), were comparatively assayed for the induction of DNA damage by determining DNA repair synthesis using polymerization inhibitors such as aphidicolin (aph) and hydroxyurea (HU). When human alveolar epithelial type II (L-132) cells in culture were exposed to either one of these three arsenic compounds, DNA single-strand breaks resulting from the inhibition of repair polymerization were remarkably produced by exposure to DMAA at 5 to 100 microM, while not by that to ARS and MMAA even at 100 microM. Furthermore, a bromodeoxyuridine (BrdrU)-photolysis assay indicated that the induction of DNA repair synthesis was observed only in the case of exposure to DMAA. When L-132 cells were exposed to 100 microM MMAA in the presence of 10 mM S-adenosyl-L-methionine (SAM), which is a well-known methyl-group donor in metabolic methylation of arsenics, DNA repair synthesis was induced along with an increase in the amount of dimethylarsenic in the cells. These results indicate that metabolic methylation of inorganic arsenics to dimethylarsenics is predominantly involved in the induction of DNA damage.

Mercury use in espiritismo: a survey of botanicas.

Zayas LH, Ozuah PO. Am J Public Health 1996 Jan;86(1):111-2

No abstract available.

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