Possible molecular mechanism of mirex-induced hepatobiliary dysfunction.
Male Sprague-Dawley rats were treated with mirex, po, at 0, 5, 10, and 50 mg/kg/day in 0.4 ml of corn oil for 3 days. Forty-eight hours after the last treatment, the biliary excretion of exogenously provided polar metabolites of 14C-imipramine was suppressed at all levels of mirex in a dose-dependent manner. Biliary excretion of phenolphthalein glucuronide was suppressed at high doses of mirex. These effects of impaired biliary excretion were accompanied by increased bile flow. Persistence of the mirex-induced biliary excretory dysfunction toward otherwise readily excretable, preformed metabolites suggests aberration of transport of these substances from the liver to bile. Whereas mitochondrial Mg++-ATPase and microsomal Na+-K+-ATPase activities were both inhibited by exposure to mirex in a dose-dependent manner, the latter activity was consistently inhibited to a higher degree. These results are suggestive of mirex-induced interference with energy production and utilization in the manifestation of hepatobiliary dysfunction.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D001660:Biliary Tract Diseases / Q000139:chemically induced*; D056486:Chemical and Drug Induced Liver Injury; D007099:Imipramine / Q000378:metabolism; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D008917:Mirex / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013997:Time Factors
D007306:Insecticides; D011453:Prostaglandins; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase; D007099:Imipramine; D008917:Mirex