S-adenosylmethionine prevents hepatic tocopherol depletion in carbon tetrachloride-injured rats.
In various experimental models, S-adenosylmethionine (SAMe) has been shown to reduce liver injury by preventing depletion of glutathione, one of the antioxidant systems that plays a critical role in defence against oxidative stress. On the other hand, alpha-tocopherol may be decreased in liver diseases, and treatment with this vitamin reduces liver injury in CCl(4)-treated rats. Since there is a close relationship among the different antioxidant systems (mainly glutathione, alpha-tocopherol and ascorbic acid), we have assessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver alpha-tocopherol and ascorbic acid levels in CCl(4)-injured rats. Four groups of seven male Wistar rats treated for 9 weeks were studied: rats induced to cirrhosis with CCl(4), rats induced to cirrhosis plus SAMe administration (10 mg x kg(-1) x day(-1)) and their respective controls. Liver samples were obtained for measuring levels of glutathione, alpha-tocopherol, ascorbic acid and thiobarbituric acid-reactive substances (TBARS), and hydroxyproline concentration as an index of collagen content. The hydroxyproline content was higher in CCl(4)-injured rats than in the control group (4.4+/-1.8 and 1.1+/-0.3 micromol/g respectively; P<0.05). In CCl(4)-injured rats, SAMe administration decreased collagen content (2.7+/-1.0 microl/g; P<0.05) and TBARS, and corrected glutathione depletion. alpha-Tocopherol was significantly lower in CCl(4)-injured rats than in controls (17.3+/-4.9 and 23.0+/-4.0 micromol/g respectively; P<0.05). By contrast, alpha-tocopherol levels were similar (23.8+/-5.1 micromol/g) in CCl(4)-injured rats receiving SAMe and in controls. In CCl(4)-injured rats, liver ascorbic acid was decreased in comparison with controls (4.9+/-1.8 and 8.2+/-1.0 micromol/g respectively; P<0.05), levels which were not replenished by SAMe (4.6+/-0.4 micromol/g). In conclusion, SAMe not only decreases fibrosis and protects against hepatic glutathione depletion, but has a further antioxidant effect of preventing alpha-tocopherol depletion in CCl(4)-injured rats.
Deulofeu
R
R
Laboratory of Biochemistry, Hospital Clínic i Provincial, University of Barcelona, Barcelona, Spain.
Parés
A
A
Rubio
M
M
Gassó
M
M
Román
J
J
Giménez
A
A
Varela-Moreiras
G
G
Caballeria
J
J
Ballesta
A M
AM
Mato
J M
JM
Rodés
J
J
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001206:Ascorbic Acid Deficiency / Q000188:drug therapy* / Q000209:etiology; D002252:Carbon Tetrachloride Poisoning / Q000150:complications*; D005978:Glutathione / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051381:Rats; D012436:S-Adenosylmethionine / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000032:analysis; D014811:Vitamin E Deficiency / Q000188:drug therapy* / Q000209:etiology
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D012436:S-Adenosylmethionine; D005978:Glutathione; D006909:Hydroxyproline