title: S-adenosylmethionine (SAMe) protects against acute alcohol induced hepatotoxicity in mice.
abstract: Although S-Adenosylmethionine (SAMe) has beneficial effects in many hepatic disorders, the effects of SAMe on acute alcohol-induced liver injury are unknown. In the present study, we investigated effects of SAMe on liver injury in mice induced by acute alcohol administration. Male C57BL/6 mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. SAMe (5 mg/kg BW) was administrated i.p. once a day for three days before ethanol administration. Subsequent serum ALT level, hepatic lipid peroxidation, enzymatic activity of CYP2E1 and hepatic mitochondrial glutathione levels were measured colorimetrically. Intracellular SAMe concentration was measured by high-performance liquid chromatography (HPLC). Histopathological changes were assessed by H&E staining. Our results showed that acute ethanol administration caused prominent microvesicular steatosis with mild necrosis and an elevation of serum ALT activity. SAMe treatment significantly attenuated the liver injury. In association with the hepatocyte injury, acute alcohol administration induced significant decreases in both hepatic SAMe and mitochondrial GSH levels along with enhanced lipid peroxidation. SAMe treatment attenuated hepatic SAMe and mitochondrial GSH depletion and lipid peroxidation following acute alcohol exposure. These results demonstrate that SAMe protects against the liver injury and attenuates the mitochondrial GSH depletion caused by acute alcohol administration. SAMe may prove to be an effective therapeutic agent in many toxin-induced liver injuries including those induced by alcohol.
authors.affiliation: Department of Medicine, University of Louisville Medical Center, 40292, Louisville, KY, USA.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Song
authors.forename: Zhanxiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Theresa
authors.initials: T
authors.lastname: Chen
authors.forename: Daniell
authors.initials: D
authors.lastname: Hill
authors.forename: James
authors.initials: J
authors.lastname: Kang
authors.forename: Shirish
authors.initials: S
authors.lastname: Barve
authors.forename: Craig
authors.initials: C
authors.lastname: McClain
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012436:S-Adenosylmethionine / Q000494:pharmacology*
chemical_list: D000431:Ethanol; D012436:S-Adenosylmethionine; D019392:Cytochrome P-450 CYP2E1