title: Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis.
abstract: 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.
authors.affiliation: Liver Unit, Hospital Clínic i Provinvial, University of Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gassó
authors.forename: M
authors.initials: M
authors.lastname: Rubio
authors.forename: G
authors.initials: G
authors.lastname: Varela
authors.forename: M
authors.initials: M
authors.lastname: Cabré
authors.forename: J
authors.initials: J
authors.lastname: Caballería
authors.forename: E
authors.initials: E
authors.lastname: Alonso
authors.forename: R
authors.initials: R
authors.lastname: Deulofem
authors.forename: J
authors.initials: J
authors.lastname: Camps
authors.forename: A
authors.initials: A
authors.lastname: Giménez
authors.forename: M
authors.initials: M
authors.lastname: Pajares
authors.forename: A
authors.initials: A
authors.lastname: Parés
authors.forename: J M
authors.initials: JM
authors.lastname: Mato
authors.forename: J
authors.initials: J
authors.lastname: Rodés
mesh_terms: 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
chemical_list: D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D012436:S-Adenosylmethionine; D003094:Collagen; D002251:Carbon Tetrachloride; D011393:Procollagen-Proline Dioxygenase; D005978:Glutathione