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

Simile, Maria Maddalena and Banni, Sebastiano and Angioni, Elisabetta and Carta, Gianfranca and De Miglio, Maria Rosaria and Muroni, Maria Rosaria and Calvisi, Diego Francesco and Carru, Angelo and Pascale, Rosa Maria and Feo, Francesco (2001) 5'-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication. Journal of Hepatology, Vol. 34 (3), p. 386-394. ISSN 0168-8278. Article.

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DOI: 10.1016/S0168-8278(00)00078-7


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: MaleWistar 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 μmol/kg), started 1 week before acute CCl4 administration or with chronic treatment, were continued up to the time of sacrifice. Results: Acute and chronic CCl 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- 1, Collagen 1 (I) and Tgf- genes in liver of chronically intoxicated rats, and TGF-β1-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.

Item Type:Article
ID Code:1193
Uncontrolled Keywords:Hydroperoxides, liver fibrosis, 5'-methylthioadenosine, antioxidant effect, liver cirrhosis, S-adenosylmethionine, Tgf-β1, Tgf-α, Collagen-α1 (I); α-Actin
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Elsevier Science Ireland
Copyright Holders:© 2001 European Association for the Study of the Liver
Deposited On:18 Aug 2009 10:04

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