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 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 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-β1, Collagen-α1 (I) and Tgf-α 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
5' Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon tetrachloride intoxication / Simile, Maria Maddalena; Banni, S; Angioni, E; Carta, G; DE MIGLIO, Maria Rosaria; Muroni, Maria Rosaria; Calvisi, Diego Francesco; Carru, A; Pascale, Rosa Maria; Feo, F.. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 34:3(2001), pp. 386-394. [10.1016/S0168-8278(00)00078-7]
5' Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon tetrachloride intoxication
SIMILE, Maria Maddalena;DE MIGLIO, Maria Rosaria;MURONI, Maria Rosaria;CALVISI, Diego Francesco;PASCALE, Rosa Maria;
2001-01-01
Abstract
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 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 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-β1, Collagen-α1 (I) and Tgf-α 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 mechanismsI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.