Abstract
Cyclosporin A is an essential immunosuppressive drug, but it is potentially toxic to the kidney and liver. Ursodeoxycholic acid, a hydrophilic bile acid, has been reported to improve cholestasis in liver disease in man. The purpose of this work was to examine whether tauroursodeoxycholate could reduce cyclosporin A-induced hepatic or renal injuries in the rat. After randomization into three groups (N=8), rats received daily for 17 days: cyclosporin A intraperitoneally alone (30 mg/kg) or cyclosporin A intraperitoneally and tauroursodeoxycholate (60 mg/kg) by gavage; controls received the cyclosporin A excipient. Under tauroursodeoxycholate, cholestastic parameters (bile flow, bile salt secretion, serum bile salts, serum bilirubin) improved significantly without affecting cyclosporin A blood levels, and excretion of the drug and its metabolites in bile increased by 47%. Serum creatinine levels were better preserved, although not significantly. These results show that tauroursodeoxycholate prevents cyclosporin A-induced cholestasis in long-term treatment in rats, possibly by facilitating the drug elimination in bile.
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This work was supported by grants from the Caisse Régionale d'Assurance Maladie du Sud-Est and Houdé Laboratories.
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Queneau, P.E., Bertault-Peres, P., Guitaoui, M. et al. Improvement of cyclosporin A-induced cholestasis by tauroursodeoxycholate in a long-term study in the rat. Digest Dis Sci 39, 1581–1585 (1994). https://doi.org/10.1007/BF02088068
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DOI: https://doi.org/10.1007/BF02088068