Enhanced total body clearance of heptachlor from rats by transstilbeneoxide

The effect of the phase II enzyme inducer, trans-stilbeneoxide (TSO; 400 mg/kg i.p. on 4 consecutive days), on the clearance of intravenously given (14C) heptachlor (2 mg/kg) was investigated in male Sprague-Dawley rats. TSO or vehicle treatment was started 4 days before (qroup I), immediately after (group II), or 4 days following (group III) heptachlor injection. Rats were sacrificed 6 days after the last TSO or vehicle dosage. In all 3 groups TSO increased cumulative excretion of heptachlor derived material in feces significantly (P<0.01) but had no effect on total urinary excretion. Pretreatment (group I) of rats with TSO resulted in elevated fecal excretion of 14C already on the first day after dosing with heptachlor, whereas the effect of the treatment was not apparent in group II and III rats until after 2 days and reached its maximum 3 days after the start of TSO administration. At termination, tissue radioactivity was significantly (P<0.05) lower in fat, kidney, brain, skin, heart and muscle, but not in serum, erythrocytes (group II and III), liver (group II and III), and spleen of TSO treated rats as compared to controls. The body burden calculated from the sum of 14C remaining in tissues was reduced to about 27% of control values. The toxicity of TSO may preclude it from considerations as a useful therapeutic agent in the treatment of chlorinated cyclodiene insecticide-exposed individuals. However, this experiment further emphasizes the importance of pharmacokinetic considerations when examining interactions in the disposition of xenobiotics. (author)