Mechanism for prevention of alcohol-induced liver injury by dietary methyl donors.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Christine L PowellIvan Rusyn

Abstract

Alcohol-induced liver injury (ALI) has been associated with, among other molecular changes, abnormal hepatic methionine metabolism, resulting in decreased levels of S-adenosylmethionine (SAM). Dietary methyl donor supplements such as SAM and betaine mitigate ALI in animal models; however, the mechanisms of protection remain elusive. It has been suggested that methyl donors may act via attenuation of alcohol-induced oxidative stress. We hypothesized that the protective action of methyl donors is mediated by an effect on the oxidative metabolism of alcohol in the liver. Male C57BL/6J mice were administered a control high-fat diet or diet enriched in methyl donors with or without alcohol for 4 weeks using the enteral alcohol feeding model. As expected, attenuation of ALI and an increase in reduced glutathione:oxidized glutathione ratio were achieved with methyl donor supplementation. Interestingly, methyl donors led to a 35% increase in blood alcohol elimination rate, and while there was no effect on alcohol metabolism in the stomach, a profound effect on liver alcohol metabolism was observed. The catalase-dependent pathway of alcohol metabolism was induced, yet the increase in CYP2E1 activity by alcohol was blunted, which may be ...Continue Reading

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Citations

Dec 4, 2010·Antioxidants & Redox Signaling·Jessica I CohenLaura E Nagy
Aug 27, 2013·Pharmacology & Therapeutics·Ivan RusynKathryn Z Guyton
Oct 11, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sheng-lei YanMei-chin Yin
Jan 29, 2016·Molecular & Cellular Proteomics : MCP·Emilie Bigaud, Fernando J Corrales
Jun 5, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Jesse LyonsKen S Lau
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Jan 13, 2016·World Journal of Gastroenterology : WJG·Kyu-Ho HanMichihiro Fukushima
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Oct 8, 2011·International Journal of Immunopathology and Pharmacology·Giovanni CorsettiR Rezzani
Jun 11, 2018·International Journal of Pharmaceutics·Thaís Gomes de CarvalhoRaimundo Fernandes de Araújo Júnior

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