Effect of dietary dieldrin on the liver and drug metabolism in the female Swiss-Vancouver mouse.
Female Swiss-Vancouver (SWV) mice, 13 weeks old, were exposed to dietary dieldrin for up to 10 weeks. Liver mass, hepatic microsomal protein and cytochrome P-450, and the in vitro metabolism of imipramine were determined at intervals. Dieldrin (5, 10, 15, and 20 ppm) caused hepatomegaly and increases in P-450; both effects were dose-related. All doses increased microsomal protein by about 30% (control value was 15.3 mg of protein per gram of liver). Maximal responses were attained by 2 weeks of exposure and maintained thereafter. Plateau liver masses at these respective doses were 111, 119, 133, and 162% of the control value (57.9 mg of liver per gram of body weight). Cytochrome P-450 was, respectively, 124, 142, 185, and 173% of the control value (0.93 nmol per milligram of microsomal protein). These changes decreased pentobarbital sleeping times by an average of 540% in animals fed 5, 15, or 25 ppm for 4 weeks. Similarly, the latency to the onset of anesthesia was increased by 26% at all doses. The N-oxidation and aryl-hydroxylation of imipramine increased with age, while demethylation decreased. The hydroxylation and demethylation of imipramine was increased after 2 and 4 weeks, respectively, of exposure to 20 ppm; N-oxidation was decreased. Longer exposure to lower doses caused similar changes. The changes in liver parameters and imipramine metabolism induced by 4 weeks exposure to 20 ppm were absent 6 weeks after exposure ceased.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004026:Dieldrin / Q000494:pharmacology*; D004032:Diet; D005260:Female; D007099:Imipramine / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size; D010573:Pesticide Residues / Q000494:pharmacology; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012018:Reflex / Q000187:drug effects
D010573:Pesticide Residues; D004364:Pharmaceutical Preparations; D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; D004026:Dieldrin; D007099:Imipramine