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S‐Adenosylmethionine Attenuates Oxidative Liver Injury in Micropigs Fed Ethanol With a Folate‐Deficient Diet
Author(s) -
Villanueva Jesus A.,
Esfandiari Farah,
White Mollie E.,
Devaraj Sridevi,
French Samuel W.,
Halsted Charles H.
Publication year - 2007
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2007.00511.x
Subject(s) - malondialdehyde , liver injury , methionine , nitrotyrosine , cyp2e1 , oxidative stress , steatohepatitis , glutathione , nitric oxide , chemistry , medicine , endocrinology , biochemistry , ethanol metabolism , alcoholic liver disease , ethanol , oxidative phosphorylation , metabolism , nitric oxide synthase , fatty liver , biology , cytochrome p450 , cirrhosis , enzyme , disease , amino acid
Background: To demonstrate a causative role for abnormal methionine metabolism in the pathogenesis of alcoholic steatohepatitis (ASH), we measured the preventive effects of supplementing folate deficient and ethanol containing diets in the micropig with S‐adenosylmethionine (SAM), a metabolite that regulates methionine metabolism. Methods: Yucatan micropigs were fed folate‐deficient diets as control, with ethanol at 40% of kcal, or with ethanol supplemented with SAM at 0.4 g/1000 kcal for 14 weeks. Histopathology, markers of liver injury, and regulatory enzymes were measured in terminal liver samples. Results: Among the ethanol group, livers showed hepatocellular necrosis together with increased levels of S‐adenosylhomocysteine (SAH) and reduced levels of SAM and its ratio to SAH and glutathione (GSH), together with increased malondialdehyde plus hydroxynonenol (MDA + HNE) and nitrotyrosine (NT), transcripts and protein levels of cytochrome P4502E1 (CYP2E1), activity of NADPH oxidase, and activity and protein levels of inducible nitric oxide (iNOS). These findings were attenuated partially or completely to control levels by SAM supplementation of the ethanol diet. Conclusions: The present results indicate that SAM supplementation attenuates ethanol induced liver injury through its effects on the expressions and activities of oxidative stress pathways, and are consistent with the concept that the pathogenesis of oxidative liver injury is regulated in part through altered hepatic methionine metabolism.