Abstract

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.

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