Inhibition of ileal bile acid transport by cyclosporin A in rat.
Chronic administration of cyclosporin A may induce cholestasis and this effect has been attributed to impaired hepatic bile salt synthesis, metabolism and transport. We investigated the effect of cyclosporin A on intestinal absorption of bile acids in the ileum of rat. Ileal bile acid absorption was measured by in vivo intestinal perfusion with cyclosporin A and the solvent Cremophor EL. During ileal perfusion with 25 microM glycocholic acid, the concentration of 2.8 mM cyclosporin A inhibited intestinal bile acid absorption on average by 34%. Additional experiments were performed with everted gut sacs of the distal ileum to evaluate active absorption. A dose and time dependent inhibition of the active intestinal absorption of bile acids was found, with a 50% transport inhibition at an average cyclosporin A concentration of 2.69 mmol L-1. Thus, cyclosporin A inhibits the active intestinal absorption of bile acids which may influence bile acid synthesis, turnover and secretion and may contribute to cyclosporin A induced cholestasis.
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002779:Cholestasis / Q000139:chemically induced; D016572:Cyclosporine / Q000633:toxicity*; D007082:Ileum / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D001647:Bile Acids and Salts; D007166:Immunosuppressive Agents; D016572:Cyclosporine