Abstract
Summary
Treatment of rats with benziodarone (50 mg/kg ip) 1 hr prior to infusion of BSP resulted in marked impairment of the biliary excretion of BSP. Total BSP concentration was decreased and this was due to a decrease in the BSP-GSH component, while unconjugated BSP concentration was increased. Benziodarone is a potent inhibitor of the S-arylglutathione transferase enzyme system which catalyses BSP conjugation with GSH. Benziodarone was found to inhibit the biliary excretion of synthetic BSP-GSH conjugates, although not that of DBSP, a BSP analog excreted without conjugation. It is proposed that benziodarone exerts its influence on BSP excretion by a combination of effects on conjugation and BSP-GSH transport, and that the results have uncovered the possibility that separate mechanisms may exist for the biliary excretion of conjugated and unconjugated dyes.
The technical assistance of Mrs. M.-Y. Guillaume is gratefully acknowledged. We are indebted to Doctor H. A. Brown Dunning, Jr. of Hynson Westcott and Dunning, Baltimore, Maryland for the donation of DBSP, and to Doctor G. Deltour of Labaz Laboratories, Brussels, Belgium for the donation of benziodarone.
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