Cyclosporin A-Induced Cholestasis in the Rat
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Cyclosporin A, a powerful immunosuppressor drug, induces nephrotoxicity and hepatotoxicity. The purpose of this study was to evaluate the ability of S-adenosyl-L-methionine (SAMe) to antagonise the cyclosporin A-induced hepatotoxicity in rats treated with cyclosporin A plus SAMe. Cyclosporin A treatment for 1 or 2 weeks increases plasma bilirubin, alters some plasma biochemical indicators of hepatic and renal function, causes cholestasis and reduces the biliary concentration and secretion of bile acid and other bile components. SAMe pretreatment and simultaneous treatment with SAMe plus cyclosporin A suppresses bilirubin increases in plasma, attenuates cholestasis and totally antagonises the adverse effects of cyclosporin A on bile acid secretion. Although cyclosporin A-induced hepatotoxicity in the rat is a multifactorial phenomenon, we suggest that the hepatoprotective effects of SAMe against cyclosporin A could be related to its regulatory function of membrane lipid composition and fluidity, either alone or combined with stimulation of the hepatic synthesis of thiol compounds.
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