5'-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication.
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 micromol/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-beta1-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.
Simile
M M
MM
Department of Biomedical Sciences, University of Sassari, Italy.
Banni
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S
Angioni
E
E
Carta
G
G
De Miglio
M R
MR
Muroni
M R
MR
Calvisi
D F
DF
Carru
A
A
Pascale
R M
RM
Feo
F
F
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology*
D000975:Antioxidants; D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D012436:S-Adenosylmethionine; D011393:Procollagen-Proline Dioxygenase