title: Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism.
abstract: Previous studies suggested that the hepatoprotective activity of betaine is associated with its effects on sulfur amino acid metabolism. We examined the mechanism by which betaine prevents the progression of alcoholic liver injury and its therapeutic potential. Rats received a liquid ethanol diet for 6 wk. Ethanol consumption elevated serum triglyceride and TNFα levels, alanine aminotransferase and aspartate aminotransferase activities, and lipid accumulation in liver. The oxyradical scavenging capacity of liver was reduced, and expression of CD14, TNFα, COX-2, and iNOS mRNAs was induced markedly. These ethanol-induced changes were all inhibited effectively by betaine supplementation. Hepatic S-adenosylmethionine, cysteine, and glutathione levels, reduced in the ethanol-fed rats, were increased by betaine supplementation. Methionine adenosyltransferase and cystathionine γ-lyase were induced, but cysteine dioxygenase was down-regulated, which appeared to account for the increment in cysteine availability for glutathione synthesis in the rats supplemented with betaine. Betaine supplementation for the final 2 wk of ethanol intake resulted in a similar degree of hepatoprotection, revealing its potential therapeutic value in alcoholic liver. It is concluded that the protective effects of betaine against alcoholic liver injury may be attributed to the fortification of antioxidant defense via improvement of impaired sulfur amino acid metabolism.
authors.affiliation: College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jung
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Kim
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kwon
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Ahn
authors.forename: Young Soon
authors.initials: YS
authors.lastname: Kim
authors.forename: Dal Woong
authors.initials: DW
authors.lastname: Choi
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000603:Amino Acids, Sulfur / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001622:Betaine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D003545:Cysteine / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements; D004798:Enzymes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000603:Amino Acids, Sulfur; D000975:Antioxidants; D004798:Enzymes; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D001622:Betaine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D005978:Glutathione; D003545:Cysteine
keywords: ALD; ALT; AST; Alcoholic liver injury; BED; BHMT; Betaine; CD; CD14; CDO; COX-2; CYP; CβS; CγL; EBD; ED; GCL; GSH; GST; Glutathione; LPS; MAT; NF-κB; Oxidative stress; ROS; S-adenosylhomocysteine; S-adenosylmethionine; SAH; SAM; TNFα; TOSC; alanine aminotransferase; alcoholic liver disease; aspartate aminotransferase; betaine-supplemented diet concomitant with ethanol intake; betaine-supplemented diet for the final 2 wk of ethanol intake; betaine–homocysteine methyltransferase; cluster of differentiation 14; control diet; cyclooxygenase-2; cystathionine β-synthase; cystathionine γ-lyase; cysteine dioxygenase; cytochrome P450; ethanol diet; glutathione; glutathione S-transferase; iNOS; inducible nitric oxide synthase; lipopolysaccharide; methionine adenosyltransferase; nuclear factor-kappaB; reactive oxygen species; total oxyradical scavenging capacity; tumor necrosis factor α; γ-glutamylcysteine ligase