Pesticide-induced modification of hepatobiliary function: hexachlorobenzene, DDT and toxaphene

The effect of pre-expose to hexachlorobenzene (HCB). toxaphene (TX) or DDT (100 ppm in the diet for 8 days in each case) on the excretory function of the bile was investigated using isolated perfused rat-liver preparations obtained from treated and control animals. Hepatic uptake, metabolism and biliary excretion of [14C]imipramine (IMP) was examined in these studies. Biliary excretion of endogenously formed metabolites of IMP was enhanced by pre-exposure to HCB, by 18% after 2 hr of perfusion. Pre-exposure to DDT and TX resulted in a decrease in biliary excretion of endogenously formed metabolites of IMP. HCB-induced enhancement of biliary excretion was not associated with either the bile flow or the rate at which IMP was metabolized. However, DDT and TX pretreatments elicited a decrease in the rate of IMP metabolism as well as in bile production, observations commensurate with the decrease in biliary excretion. Biliary excretion of exogenously provided, readily excretable metabolites of IMP was decreased by pre-exposure to HCB as well as to DDT or TX. In the light of these observations an alternative mechanism for HCB-induced modification of biliary excretion has been proposed. This mechanism assumes the existence of a 'synthetic' and a 'post-synthetic' pool of metabolites, the biliary removal of metabolites from each of these pools being subject to modification by HCB. An enhancement of the biliary excretion of IMP metabolites from the 'synthetic' pool and impairment of removal from the 'post-synthetic' pool would be consistent with the above results. (author)