MIREX-INDUCED IMPAIRMENT OF HEPATOBILIARY FUNCTION - SUPPRESSED BILIARY-EXCRETION OF IMIPRAMINE AND SULFOBROMOPHTHALEIN

  • 1 January 1977
    • journal article
    • research article
    • Vol. 5  (1) , 56-62
Abstract
Effect of pre-exposure to the pesticide mirex on hepatic uptake, metabolism and biliary excretion of the tricyclic antidepressant, imipramine (IMP), was studied by using isolated perfused rat liver preparations obtained from control and treated animals. Pretreatment of male rats with mirex (50 mg/kg per day, po [by mouth], for 3 days) resulted in a marked suppression (91%) of biliary excretion of endogenously formed polar metabolites of IMP. This impairment of biliary excretory function is related neither to to the bile flow nor to the rate of metabolism of IMP. These conclusions are supported by the following observations: pre-exposure to mirex results in a significant increase in bile secretion; endogenously formed metabolites of IMP accumulate in increasing concentrations in the perfusate of liver preparations from mirex-treated rats, and and over 98% of the IMP was meatabolized by livers of both control and mirex-treated rats. Biliary excretion of exogenously provided polar metabolites of IMP was also suppressed by 88% of that of control livers. Addition of mirex (5 .times. 10-5 M) to the perfusate of control liver preparations was without effect on biliary excretion of IMP metabolites. Biliary excretion of sulfobromophthalein was also markedly suppressed (90%) by preexposure to mirex. Mirex-induced impairment of hepatobiliary function is apparently not specific to substrates. The mechanism of mirex-induced impairment is located at the site of transfer of otherwise readily excretable substances such as metabolites of IMP and sulfobromophthalein.