5′-methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication

被引:93
作者
Simile, MM
Banni, S
Angioni, E
Carta, G
De Miglio, MR
Muroni, MR
Calvisi, DF
Carru, A
Pascale, RM
Feo, F
机构
[1] Univ Sassari, Sezione Patol Sperimentale & Oncol, Dept Biomed Sci, Div Expt Pathol & Oncol, I-07100 Sassari, Italy
[2] Univ Cagliari, Dept Expt Biol, Div Expt Pathol, Cagliari, Italy
关键词
hydroperoxides; liver fibrosis; 5 '-methylthioadenosine; antioxidant effect; liver cirrhosis; S-adenosyl-methionine; Tgf-beta; 1; Tgf-alpha; collagen-alpha 1 (I); alpha-actin;
D O I
10.1016/S0168-8278(00)00078-7
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: 5'-Methylthioadenosine (MTA) a product of S-adenosylmethionine (SAM) catabolism, could undergo oxidation by mono-oxygenases and auto-oxidation, MTA and SAM effects on oxidative liver injury were evaluated in CCl4-treated rats. Methods: Male Wistar rats were killed 1-48 h after poisoning with a single intraperitoneal CCl4 dose (0.15 ml/100 g) or with the same dose twice a week for 14 weeks. Daily doses of MTA or SAM (384 mu mol/kg), started 1 week before acute CCl4 administration or with chronic treatment, were continued up to the time of sacrifice. Results: Acute and chronic CCl4 intoxication decreased MTA and, to a lesser extent, SAM and reduced glutathione (GSH) liver levels. MTA administration increased liver MTA without affecting SAM and GSH. SAM treatment caused complete/partial recovery of these compounds, MTA and, to a lesser extent, SAM prevented an increase in liver phospholipid hydroperoxides in acutely and chronically intoxicated rats and in prolyl hydroxylase activity and trichrome-positive areas in chronically treated rats. MTA prevented upregulation of Tgf-beta1, Collagen-alpha1 (I) and Tgf-alpha genes in liver of chronically intoxicated rats, and TGF-betal-induced transdifferentiation to myofibroblasts and growth stimulation by platelet-derived growth factor-b of stellate cells in vitro. Conclusions: MTA and SAM protect against oxidative liver injury through partially different mechanisms. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B,V, All rights reserved.
引用
收藏
页码:386 / 394
页数:9
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