Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis.
OBJECTIVE
The aim of this study was to investigate the effects of S-adenosylmethionine on liver peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis.


METHODS
Cirrhosis was induced in three groups of six rats by repeated injections of carbon tetrachloride over 9 weeks. One group of animals was treated only with carbon tetrachloride, and the other two received carbon tetrachloride plus S-adenosylmethionine (10 mg/kg intramuscularly daily) from week 3 to week 9, and from week 6 to week 9 of the study, respectively. Two additional groups of six rats, a control group and a group treated only with S-adenosylmethionine, were also studied. Glutathione concentration, thiobarbituric acid-reactive substances, collagen content, prolyl hydroxylase activity, and procollagen type I mRNA expression were determined in liver samples.


RESULTS
All carbon tetrachloride-treated rats had cirrhosis at the end of the study. Cirrhosis was also present in five of the six carbon tetrachloride-treated rats receiving S-adenosylmethionine for 3 weeks, but in only one of the six rats that received S-adenosylmethionine for 6 weeks. Hepatic glutathione was significantly diminished in carbon tetrachloride-treated rats (2.7 +/- 0.3 mumol/g tissue) and returned to normal in rats receiving S-adenosylmethionine for 3 or 6 weeks (3.7 +/- 0.13 and 3.9 +/- 0.11 mumol/g tissue, respectively). The hepatic thiobarbituric acid-reactive substances were significantly lower in rats treated with carbon tetrachloride and S-adenosylmethionine for 6 weeks (98 +/- 5 nmol/g) than in rats treated with carbon tetrachloride (134 +/- 12 nmol/g) and in those treated with carbon tetrachloride and S-adenosylmethionine for 3 weeks (127 +/- 13 nmol/g). There were no differences in either hepatic collagen and prolyl hydroxylase activity between rats that received only carbon tetrachloride and those treated with S-adenosylmethionine for 3 weeks. In contrast, carbon tetrachloride-treated rats receiving S-adenosylmethionine for 6 weeks had significantly lower collagen and prolyl hydroxylase activity than the other two groups. A much greater increase in procollagen type I mRNA was found in carbon tetrachloride-treated rats than in rats treated with carbon tetrachloride and S-adenosylmethionine for 6 weeks. Furthermore, there was a significant correlation between the hepatic thiobarbituric acid-reactive substances and prolyl hydroxylase activity and hepatic collagen.


CONCLUSIONS
We conclude that the early administration of S-adenosylmethionine in a model of carbon tetrachloride-induced liver injury restores glutathione levels and reduces lipid peroxidation, resulting in less advanced liver fibrosis.
Gassó
M
M
Liver Unit, Hospital Clínic i Provinvial, University of Barcelona, Spain.
Rubio
M
M
Varela
G
G
Cabré
M
M
Caballería
J
J
Alonso
E
E
Deulofem
R
R
Camps
J
J
Giménez
A
A
Pajares
M
M
Parés
A
A
Mato
J M
JM
Rodés
J
J
D000818:Animals; D002251:Carbon Tetrachloride; D003094:Collagen / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D012436:S-Adenosylmethionine; D003094:Collagen; D002251:Carbon Tetrachloride; D011393:Procollagen-Proline Dioxygenase; D005978:Glutathione