Cyclosporin A and Enterohepatic Circulation of Bile Salts in Rats: Decreased Cholate Synthesis but Increased Intestinal Reabsorption

作者: Christian V. Hulzebos , Henk Wolters , Torsten Plösch , Werner Kramer , Siegfried Stengelin

DOI: 10.1124/JPET.102.041640

关键词:

摘要: Cyclosporin A (CsA) has been shown to inhibit synthesis and hepatobiliary transport of bile salts. However, effects CsA on the enterohepatic circulation salts in vivo are largely unknown. We characterized cholate, with respect rate, pool size, cycling time, intestinal absorption, expression relevant transporters liver intestine rats. (1 mg. 100 g(-1). day(-1) s.c.) or its solvent was administered daily male rats for 10 days. Cholate rate size were determined by a 2H4-cholate dilution technique. Bile feces collected determination cholate total salts, respectively. Cycling time absorption calculated. The mRNA levels corresponding transporter protein assessed real-time polymerase chain reaction Western analysis, treatment decreased 71%, but did not affect time. reduced amount lost per cycle approximately 70%. Protein apical sodium-dependent salt (Asbt) 2-fold increased distal ileum CsA-treated rats, due post-transcriptional events. In conclusion, chronic markedly reduces does Our results strongly suggest that enhances efficacy reabsorption through Asbt ileum, which contributes maintenance

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