Abstract

This study examines the ability of S-adenosyl-L-methionine to prevent or antagonize the cyclosporine A-induced adverse effects on biliary secretion in the rat. S-adenosyl-L-methionine was administered as a single bolus 3, 5 and 8 hr before administering a single dose of cyclosporine A, and also concurrently administered with cyclosporine A for 1 or 2 wk. Acute S-adenosyl-L-methionine preadministration attenuated the cyclosporine-induced cholestasis and inhibition of bile acids, cholesterol and phospholipid biliary secretion. S-adenosyl-L-methionine pretreatment for 1 wk and simultaneous cotreatment with cyclosporine for 1 or 2 wk not only maintained the beneficial effects reported above but further improved them because the adverse effects of the immunosuppressor drug were prevented or antagonized by S-adenosyl-L-methionine. These results provide the first direct evidence of the ability of exogenously administered S-adenosyl-L-methionine to antagonize cyclosporine-induced abnormalities in biliary bile acids, lipids and protein secretion. The beneficial effects of S-adenosyl-L-methionine could be related, at least in part, to the improvement in the hepatobiliary transport of bile acids.