Effects of S-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats.
We used an animal model of extrahepatic biliary obstruction of 7 days' duration to study the production of thiobarbituric acid reactive substances (TBARS), total glutathione (TG), reduced glutathione (GSH), and oxidized glutathione (GSSG), and the enzymatic activities of GSH-peroxidase, GSSG-reductase, and GSH-transferase. Four groups of six rats each were treated with saline, drug solvent, S-adenosyl-L-methionine (SAM) 5 mg/kg/d, subcutaneously, or SAM 10 mg/kg/d, subcutaneously. Extrahepatic biliary obstruction increased TBARS. SAM had the dose-dependent effects of inhibiting TBARS production and increasing TG content, mainly as a result of the increase in GSH. The activity of GSH-peroxidase and GSH-transferase was also significantly increased. In renal tissue these effects were statistically significant only in animals given the higher dose of SAM. In liver we found a reduction in biochemical values indicative of liver damage. We conclude that effect of SAM on hepatorenal function is strongly influenced by the drug's ability to reestablish equilibrium after oxidative tissue stress.
Gonzalez-Correa
J A
JA
Department of Pharmacology and Therapeutics, School of Medicine, University of Malaga, Spain.
De La Cruz
J P
JP
Martin-Aurioles
E
E
Lopez-Egea
M A
MA
Ortiz
P
P
Sanchez de la Cuesta
F
F
D000818:Animals; D001651:Cholestasis, Extrahepatic / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D012436:S-Adenosylmethionine; D005978:Glutathione