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And alt mercury detox doesn't do anything in rats

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- Hide quoted text — Show quoted text –       1: J Toxicol Clin Toxicol. 2003;41(4):339-47.  Related       Articles, Links Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor. No surprise. How the heck would Vitamin C bind Hg2+? It’s just incredible what some people expect from vitamines. What’s next? Someone will claim that Vitamin C makes immune against radiation? http://www.thorne.com/altmedrev/fulltext/lipoic.html Alpha-Lipoic Acid: Biological Effects and Clinical Implications

Opened all flood gates to flush out vast amount of sewage.

Response:

      1: J Toxicol Clin Toxicol. 2003;41(4):339-47.  Related Articles,       Links Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor.

No surprise. How the heck would Vitamin C bind Hg2+? It’s just incredible what some people expect from vitamines. What’s next? Someone will claim that Vitamin C makes immune against radiation?

Response:

- Hide quoted text — Show quoted text –       1: J Toxicol Clin Toxicol. 2003;41(4):339-47.  Related Articles,       Links Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor. No surprise. How the heck would Vitamin C bind Hg2+? It’s just incredible what some people expect from vitamines. What’s next? Someone will claim that Vitamin C makes immune against radiation?

http://www.thorne.com/altmedrev/fulltext/lipoic.html Alpha-Lipoic Acid: Biological Effects and Clinical Implications Trent W. Nichols, Jr. M.D. Abstract Alpha-lipoic acid is unique in its ability to act as an antioxidant in fat- and water-soluble tissues in both its oxidized and reduced forms. It is readily absorbed from an oral dose. Because of its myriad biological activities, including an ability to chelate metals and to scavenge a wide array of free radicals, alpha-lipoic acid is considered by several experts to be an ideal antioxidant. Clinical applications for this nutrient include the following conditions: diabetic polyneuropathy, cataracts, glaucoma, ischemia-reperfusion injury, and Amanita mushroom poisoning. Because of its unique characteristics alpha-lipoic acid is likely to have therapeutic application in a wide range of additional clinical conditions. (Alt Med Rev 1997; 2(3):177-183) Introduction Alpha-lipoic acid, first isolated in 1951 by Reed and coworkers as a catalytic agent associated with pyruvate dehydrogenase, is known by a variety of names, including 2-dithiolane-3 pentanoic acid; 1,2-dithiolane-3 valeric acid; and thioctic acid.1 It was originally classified as a vitamin; however, it subsequently was found to be synthesized by animals and humans.2 Although the enzyme pathway for its de novo synthesis has not been fully elucidated, cysteine appears to be the source of sulfur, and octanoate serves as the intermediate precursor for the 8-carbon fatty acid.3 It is readily converted to its reduced form, dihydrolipoic acid (DHLA), in many tissues of the body. Antioxidant Activity Alpha-lipoic acid is unique in its ability to act as an antioxidant in fat- and water-soluble tissues in both its oxidized and reduced forms. It is also readily absorbed from an oral dose. Because of these advantages and its low toxicity, alpha-lipoic acid is receiving increased attention as a potentially effective therapeutic agent in clinical conditions associated with free radical damage. Lester Packer, PhD, of the University of California at Berkeley, has suggested alpha-lipoic acid is an ideal antioxidant candidate because of its role in the following: specificity of free radical quenching, metal chelating activity, interaction with other antioxidants, and effects on gene expression.4 An antioxidant function for alpha-lipoic acid was discovered in 1959 by Rosenberg and Culik, who reported it prevented both scurvy symptoms in vitamin C-deficient guinea pigs and vitamin E deficiency in rats fed a diet lacking a-tocopherol.5 Podda et al reported alpha-lipoic acid prevents symptoms of vitamin E deficiency in mice fed a vitamin E-deficient diet; however, it had no effect on sustaining vitamin E tissue concentrations.6 Experimental evidence indicates optimal reduction of dehydroascorbic to ascorbic acid is achieved in the presence of pyruvate, alpha-lipoic acid, and ATP.7 Alpha-lipoic acid has a low redox potential, and through its reduced form, DHLA, very readily donates electrons to other compounds. Ascorbic acid, and indirectly vitamin E, are thought to be regenerated by DHLA.8 (See Figure 2.) Busse et al found alpha-lipoic acid can cause an increase in intracellular glutathione.9 DHLA can regenerate Coenzyme Q10, and NADPH or NADH via glutathione.10 Experts are in general agreement that alpha-lipoic acid is capable of scavenging hydroxyl radicals, hypochlorous acid, and singlet oxygen, but not hydrogen peroxide, peroxyl, and superoxide.4,11-13 DHLA is both an antioxidant and prooxidant in studies where hydroxyl radicals were generated. It protects against single strand DNA breaks induced by singlet oxygen, although it does not do so directly and several steps might be involved in the process.13 Sandhya et al indicate alpha-lipoic acid acts in a dose-dependent manner as a nephroprotective agent against experimentally induced gentamicin toxicity.14 Metal Chelation Alpha-lipoic acid appears capable of chelating transition metals in biological systems. It forms stable complexes with copper, manganese and zinc ions.15 Its ability to chelate iron remains equivocal.16,17 Mice were protected from arsenite poisoning with alpha-lipoic acid administration when the ratio of alpha-lipoic acid to arsenite was at least 8:1. Protection occurred even if the administration was after severe symptoms of poisoning were present.18 Evidence suggests alpha-lipoic acid might chelate copper. Ou et al report the R-enantiomer and racemic mixture of alpha-lipoic acid seemed more effective than the S-enantiomer in their assays of metal chelation.19 In isolated hepatocytes, alpha-lipoic acid has been found to reduce cadmium-induced toxicity, although DHLA was much more effective.20 Sumathi et al also reported alpha-lipoic acid offers significant hepatoprotection against cadmium toxicity, even under glutathione-depleted experimental conditions.21 In a rat model, a dose of 30 mg of alpha-lipoic acid completely prevented cadmium-induced lipid peroxidation in the brain, heart, and testicles.22 In vitro experiments have indicated alpha-lipoic acid, while not the most effective chelating agent, will remove mercury from renal slices.23 alpha-lipoic acid administration to rats increased biliary excretion of injected mercury 12-37 fold but decreased the excretion of cadmium, zinc, copper, and methylmercury.24 Clinical Implications Diabetes: Because many of the systemic complications of diabetes mellitus, such as polyneuropathy and cataract formation, appear to be secondary to free radical damage, alpha-lipoic acid and DHLA have been proposed as possible therapeutic agents in these conditions. In heart tissue of diabetic rats, high doses of alpha-lipoic acid first normalized glucose uptake and utilization, and consequently normalized oxygen uptake, myocardial ATP levels, and cardiac output, while a low dose of alpha-lipoic acid normalized lactate and pyruvate production.25 In cell cultures, alpha-lipoic acid stimulated basal glucose transport and had a positive effect on insulin-stimulated glucose uptake.26 alpha-lipoic acid administration prevented diabetes in 70% of diabetes induced animals. This effect was thought to be secondary to DHLA suppression of nitric oxide release from macrophages involved in islet cell inflammation.27 In a type II diabetic model using insulin-resistant obese Zucker rats, alpha-lipoic acid increased the uptake of glucose in the absence of insulin.28 Glycation of protein caused by elevated blood and tissue glucose is believed to contribute to many of the complications seen in diabetes. These sugar-damaged proteins are referred to as advanced glycosylation end products (AGEs). AGEs increase with the length of hyperglycemia and are thought to be responsible for the kidney damage and advanced atherosclerosis seen in diabetes.4 Packer and Kawabata found noncovalent binding of alpha-lipoic acid to albumin protected proteins against glycation.29 Type II diabetic humans given an acute dose of alpha-lipoic acid (1000 mg intravenously) experienced 50% improvement in insulin-stimulated glucose disposal.30 In an uncontrolled pilot study 20 patients with type II diabetes received daily alpha-lipoic acid (500 mg/500 ml NaCl, 0.9%) parenterally for ten days. An increase of insulin-stimulated glucose disposal of approximately 30% was reported; however, no changes in fasting plasma levels for glucose or insulin were found during the short period of treatment and observation.31 Diabetic polyneuropathy has been treated clinically in Germany with alpha-lipoic acid for over 20 years. Findings indicate alpha-lipoic acid can correct neuropeptide deficits in diabetic rats.32 A model of streptozotocin-induced diabetic neuropathy was evaluated using alpha-lipoic acid and measuring improved nerve blood flow (NBF) after one month in age controlled rats. The alpha-lipoic acid-supplemented rats exhibited normal NBF.33 A three-week multicenter double-blind, placebo-controlled trial of alpha-lipoic acid administered intravenously at 1200, 600, or 100 mg was conducted in patients with diabetic neuropathy. Symptom scoring including pain, burning, paresthesia, and numbness was conducted at baseline and at each visit. Intravenous treatment with 600 mg/day for three weeks was superior to placebo in reducing symptoms of neuropathy and caused no significant adverse reactions.34 In a non-blinded study of diabetic patients with both type I and II diabetes, 600 mg/day of alpha-lipoic acid was given for two weeks, followed by 300 mg/day for 10 weeks. Albuminuria decreased 50% as compared to placebo controls. A clinical improvement in neurological symptoms was found in the alpha-lipoic acid group but not in the control group.35 Cataracts: High levels of activity of the enzyme aldose reductase have been associated with diabetic cataracts. Aldose reductase is inhibited by alpha-lipoic acid in rat lenses.36 Dietary supplementation of alpha-lipoic acid has been shown to prevent cataract formation caused by buthionine sulfoximine-induced (BSO) inhibition of glutathione synthesis in newborn rats.37 The protective effects of alpha-lipoic acid against BSO-induced cataract appear to be stereospecific. Both a racemic mixture and R-alpha-lipoic acid were able to … read more »

Response:

- Hide quoted text — Show quoted text –      1: J Toxicol Clin Toxicol. 2003;41(4):339-47.  Related Articles, Links Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor. Aposhian HV, Morgan DL, Queen HL, Maiorino RM, Aposhian MM. Department of Molecular and Cellular Biology, The University of Arizona, Some medical practitioners prescribe GSH and vitamin C alone or in combination with DMPS or DMSA for patients with mercury exposure that is primarily due to the mercury vapor emitted by dental amalgams. HYPOTHESIS: This study tested the hypothesis that GSH, vitamin C, or lipoic acid alone or in combination with DMPS or DMSA would decrease brain mercury. METHODS: Young rats were exposed to elemental mercury by individual nose cone, at the rate of 4.0 mg mercury per m3 air for 2 h per day for 7 consecutive days. After a 7-day equilibrium period, DMPS, DMSA, GSH, vitamin C, lipoic acid alone, or in combination was administered for 7 days and the brain and kidneys of the animals removed and analyzed for mercury by cold vapor atomic absorption. RESULTS: None of these regimens reduced the mercury content of the brain. Although DMPS or DMSA was effective in reducing kidney mercury concentrations, GSH, vitamin C, lipoic acid alone, or in combination were not. CONCLUSION: One must conclude that the palliative effect, if any, of GSH, vitamin C, or lipoic acid for treatment of mercury toxicity due to mercury vapor exposure does not involve mercury mobilization from the brain and kidney.

http://www.thorne.com/altmedrev/fulltext/lipoic.html Alpha-Lipoic Acid: Biological Effects and Clinical Implications Trent W. Nichols, Jr. M.D. Abstract Alpha-lipoic acid is unique in its ability to act as an antioxidant in fat- and water-soluble tissues in both its oxidized and reduced forms. It is readily absorbed from an oral dose. Because of its myriad biological activities, including an ability to chelate metals and to scavenge a wide array of free radicals, alpha-lipoic acid is considered by several experts to be an ideal antioxidant. Clinical applications for this nutrient include the following conditions: diabetic polyneuropathy, cataracts, glaucoma, ischemia-reperfusion injury, and Amanita mushroom poisoning. Because of its unique characteristics alpha-lipoic acid is likely to have therapeutic application in a wide range of additional clinical conditions. (Alt Med Rev 1997; 2(3):177-183) Introduction Alpha-lipoic acid, first isolated in 1951 by Reed and coworkers as a catalytic agent associated with pyruvate dehydrogenase, is known by a variety of names, including 2-dithiolane-3 pentanoic acid; 1,2-dithiolane-3 valeric acid; and thioctic acid.1 It was originally classified as a vitamin; however, it subsequently was found to be synthesized by animals and humans.2 Although the enzyme pathway for its de novo synthesis has not been fully elucidated, cysteine appears to be the source of sulfur, and octanoate serves as the intermediate precursor for the 8-carbon fatty acid.3 It is readily converted to its reduced form, dihydrolipoic acid (DHLA), in many tissues of the body. Antioxidant Activity Alpha-lipoic acid is unique in its ability to act as an antioxidant in fat- and water-soluble tissues in both its oxidized and reduced forms. It is also readily absorbed from an oral dose. Because of these advantages and its low toxicity, alpha-lipoic acid is receiving increased attention as a potentially effective therapeutic agent in clinical conditions associated with free radical damage. Lester Packer, PhD, of the University of California at Berkeley, has suggested alpha-lipoic acid is an ideal antioxidant candidate because of its role in the following: specificity of free radical quenching, metal chelating activity, interaction with other antioxidants, and effects on gene expression.4 An antioxidant function for alpha-lipoic acid was discovered in 1959 by Rosenberg and Culik, who reported it prevented both scurvy symptoms in vitamin C-deficient guinea pigs and vitamin E deficiency in rats fed a diet lacking a-tocopherol.5 Podda et al reported alpha-lipoic acid prevents symptoms of vitamin E deficiency in mice fed a vitamin E-deficient diet; however, it had no effect on sustaining vitamin E tissue concentrations.6 Experimental evidence indicates optimal reduction of dehydroascorbic to ascorbic acid is achieved in the presence of pyruvate, alpha-lipoic acid, and ATP.7 Alpha-lipoic acid has a low redox potential, and through its reduced form, DHLA, very readily donates electrons to other compounds. Ascorbic acid, and indirectly vitamin E, are thought to be regenerated by DHLA.8 (See Figure 2.) Busse et al found alpha-lipoic acid can cause an increase in intracellular glutathione.9 DHLA can regenerate Coenzyme Q10, and NADPH or NADH via glutathione.10 Experts are in general agreement that alpha-lipoic acid is capable of scavenging hydroxyl radicals, hypochlorous acid, and singlet oxygen, but not hydrogen peroxide, peroxyl, and superoxide.4,11-13 DHLA is both an antioxidant and prooxidant in studies where hydroxyl radicals were generated. It protects against single strand DNA breaks induced by singlet oxygen, although it does not do so directly and several steps might be involved in the process.13 Sandhya et al indicate alpha-lipoic acid acts in a dose-dependent manner as a nephroprotective agent against experimentally induced gentamicin toxicity.14 Metal Chelation Alpha-lipoic acid appears capable of chelating transition metals in biological systems. It forms stable complexes with copper, manganese and zinc ions.15 Its ability to chelate iron remains equivocal.16,17 Mice were protected from arsenite poisoning with alpha-lipoic acid administration when the ratio of alpha-lipoic acid to arsenite was at least 8:1. Protection occurred even if the administration was after severe symptoms of poisoning were present.18 Evidence suggests alpha-lipoic acid might chelate copper. Ou et al report the R-enantiomer and racemic mixture of alpha-lipoic acid seemed more effective than the S-enantiomer in their assays of metal chelation.19 In isolated hepatocytes, alpha-lipoic acid has been found to reduce cadmium-induced toxicity, although DHLA was much more effective.20 Sumathi et al also reported alpha-lipoic acid offers significant hepatoprotection against cadmium toxicity, even under glutathione-depleted experimental conditions.21 In a rat model, a dose of 30 mg of alpha-lipoic acid completely prevented cadmium-induced lipid peroxidation in the brain, heart, and testicles.22 In vitro experiments have indicated alpha-lipoic acid, while not the most effective chelating agent, will remove mercury from renal slices.23 alpha-lipoic acid administration to rats increased biliary excretion of injected mercury 12-37 fold but decreased the excretion of cadmium, zinc, copper, and methylmercury.24 Clinical Implications Diabetes: Because many of the systemic complications of diabetes mellitus, such as polyneuropathy and cataract formation, appear to be secondary to free radical damage, alpha-lipoic acid and DHLA have been proposed as possible therapeutic agents in these conditions. In heart tissue of diabetic rats, high doses of alpha-lipoic acid first normalized glucose uptake and utilization, and consequently normalized oxygen uptake, myocardial ATP levels, and cardiac output, while a low dose of alpha-lipoic acid normalized lactate and pyruvate production.25 In cell cultures, alpha-lipoic acid stimulated basal glucose transport and had a positive effect on insulin-stimulated glucose uptake.26 alpha-lipoic acid administration prevented diabetes in 70% of diabetes induced animals. This effect was thought to be secondary to DHLA suppression of nitric oxide release from macrophages involved in islet cell inflammation.27 In a type II diabetic model using insulin-resistant obese Zucker rats, alpha-lipoic acid increased the uptake of glucose in the absence of insulin.28 Glycation of protein caused by elevated blood and tissue glucose is believed to contribute to many of the complications seen in diabetes. These sugar-damaged proteins are referred to as advanced glycosylation end products (AGEs). AGEs increase with the length of hyperglycemia and are thought to be responsible for the kidney damage and advanced atherosclerosis seen in diabetes.4 Packer and Kawabata found noncovalent binding of alpha-lipoic acid to albumin protected proteins against glycation.29 Type II diabetic humans given an acute dose of alpha-lipoic acid (1000 mg intravenously) experienced 50% improvement in insulin-stimulated glucose disposal.30 In an uncontrolled pilot study 20 patients with type II diabetes received daily alpha-lipoic acid (500 mg/500 ml NaCl, 0.9%) parenterally for ten days. An increase of insulin-stimulated glucose disposal of approximately 30% was reported; however, no changes in fasting plasma levels for glucose or insulin were found during the short period of treatment and observation.31 Diabetic polyneuropathy has been treated clinically in Germany with alpha-lipoic acid for over 20 years. Findings indicate alpha-lipoic acid can correct neuropeptide deficits in diabetic rats.32 A model of streptozotocin-induced diabetic neuropathy was evaluated using alpha-lipoic acid and measuring improved nerve blood flow (NBF) after one month in age controlled rats. The alpha-lipoic acid-supplemented rats exhibited normal NBF.33 A three-week multicenter double-blind, placebo-controlled trial of alpha-lipoic acid administered intravenously at 1200, 600, or 100 mg was conducted in patients with diabetic neuropathy. Symptom scoring including … read more »

Response:

      1: J Toxicol Clin Toxicol. 2003;41(4):339-47.  Related Articles, Links Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor. Aposhian HV, Morgan DL, Queen HL, Maiorino RM, Aposhian MM. Department of Molecular and Cellular Biology, The University of Arizona, Some medical practitioners prescribe GSH and vitamin C alone or in combination with DMPS or DMSA for patients with mercury exposure that is primarily due to the mercury vapor emitted by dental amalgams. HYPOTHESIS: This study tested the hypothesis that GSH, vitamin C, or lipoic acid alone or in combination with DMPS or DMSA would decrease brain mercury. METHODS: Young rats were exposed to elemental mercury by individual nose cone, at the rate of 4.0 mg mercury per m3 air for 2 h per day for 7 consecutive days. After a 7-day equilibrium period, DMPS, DMSA, GSH, vitamin C, lipoic acid alone, or in combination was administered for 7 days and the brain and kidneys of the animals removed and analyzed for mercury by cold vapor atomic absorption. RESULTS: None of these regimens reduced the mercury content of the brain. Although DMPS or DMSA was effective in reducing kidney mercury concentrations, GSH, vitamin C, lipoic acid alone, or in combination were not. CONCLUSION: One must conclude that the palliative effect, if any, of GSH, vitamin C, or lipoic acid for treatment of mercury toxicity due to mercury vapor exposure does not involve mercury mobilization from the brain and kidney.

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