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Medical Forum / General / General / June 2005Neuroprotection / folate / vitamin E / iron overload
Neuromolecular Med. 2004;6(2-3):93-104. Links Dietary supplementation with 3-deaza adenosine, N-acetyl cysteine, and s-adenosyl methionine provide neuroprotection against multiple consequences of vitamin deficiency and oxidative challenge: relevance to age-related neurodegeneration. Tchantchou F, Graves M, Ortiz D, Rogers E, Shea TB. Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA. Folate deprivation induces neurotoxicity that is potentiated by additional nutritional and genetic deficiencies including vitamin E and apolipoprotein E deficiency. These deficiencies collectively induce oxidative damage, cognitive impairment, and compensatory alteration in glutathione generation. Treatment with agents that regulate distinct portions of the methionine cycle, including the S-adenosyl homocysteine hydrolase inhibitor, 3-deaza adenosine, the methyl donor S-adenosyl methionine, and the antioxidant N-acetyl cysteine, provide neuroprotection against various aspects of neurotoxicity in normal and apolipoprotein E-deficient mice and in cultured neuronal cells deprived of dietary folate and vitamin E and subjected to iron overload. Here it is demonstrated that simultaneous treatment with these agents provide superior neuroprotection by alleviating individual and overlapping neurotoxic consequences. These findings support combinatorial treatments with agents that compenate for differential insults in age-related neurodegenerative disorders. PMID: 15970627 [PubMed - in process] -------------------------------------------------------------------------------- Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking Alcohol Alcohol. 2003 May-Jun;38(3):208-12. Related Articles, Links Polyenylphosphatidylcholine corrects the alcohol-induced hepatic oxidative stress by restoring s-adenosylmethionine. Aleynik SI, Lieber CS. Alcohol Research Center, Section of Liver Disease and Nutrition, Bronx VA Medical Center and Mount Sinai School of Medicine, New York, NY, USA. AIMS: Since the late stages of alcoholic liver injury are associated with decreased activity of methionine adenosyltransferase (MAT), we wondered whether this already occurs at the early stages and what is the mechanism involved. METHODS: Sprague-Dawley rats (n = 32) were pair-fed ethanol (36% of energy) or isocaloric carbohydrates (control) in Lieber-DeCarli liquid diets, with or without polyenylphosphatidylcholine (PPC). RESULTS: After 2 months, there was a striking depletion of S-adenosylmethionine (measured by high-performance liquid chromatography) from 68.2 +/- 5.1 to 36.2 +/- 3.4 nmol/g, associated with a reduction in hepatic reduced glutathione (GSH) from 4.95 +/- 0.20 to 4.09 +/- 0.08 micro mol/g, and an increase from 0.24 +/- 0.02 to 0.47 +/- 0.07 nmol/g of 4-hydroxynonenal (4-HNE), a reliable marker of lipid peroxidation. Hepatic S-adenosylmethionine (SAMe) correlated positively with GSH (r = 0.5916) and negatively with 4-HNE (r = -0.6375). Feeding PPC corrected all values and MAT activity did not differ significantly between groups. CONCLUSIONS: SAMe depletion occurs already after 8 weeks of alcohol feeding and is fully corrected by PPC, in parallel with the prevention by PPC of the alcohol-induced oxidative stress. Since phosphatidylcholines (PCs) are produced in the liver via methylation of phosphatidylethanolamine by SAMe, it is likely that PPC, by providing PCs, decreases the utilization of SAMe and thereby contributes to its restoration, with replenishment of GSH and correction of the alcohol-induced oxidative stress. PMID: 12711653 [PubMed - indexed for MEDLINE] -------------------------------------------------------------------------------- Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking |
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