DDVP (dichlorvos) detoxification by binding and interactions with DDT, dieldrin, and malaoxon.
Binding to tissue carboxylesterases has been suggested as an important mechanism of detoxification for several organophosphates. In this study DDVP, malaoxon, and paraoxon were inactivated, in vitro, by mouse liver under assay conditions that were consistent with a binding mechanism of inactivation. Binding of the three organophosphates was inhibited in livers of mice pretreated, 18 hr before sacrifice, with TOTP (triorthotolyl phosphate, 125 mg/kg, ip). Previous studies have shown that similar TOTP treatment enhanced the toxicity of malaoxon and paraoxon but did not alter the toxicity of DDVP. Both DDT (50 mg/kg, ip, given 4, 3.5, and 2.5 days before sacrifice) and dieldrin (16 mg/kg, po, given 4 days before sacrifice) increased liver/body weight ratios and decreased the duration of pentobarbital-induced loss of righting ability. Dieldrin increased liver carboxylesterase activity and liver binding of malaoxon and paraoxon but not of DDVP. In contrast, DDT did not increase liver carboxylesterase activity nor did it increase binding of malaoxon or paraoxon. Yet DDT pretreatment increased mouse liver binding of DDVP. Neither DDT nor dieldrin pretreatments altered the toxicity of subsequently administered DDVP. These results support the hypothesis that carboxylesterase binding does not represent an important mechanism for DDVP detoxification in the mouse. In other experiments, in vitro inactivation of malaoxon by binding was inhibited in livers of mice given DDVP (30 mg/kg, ip) 30 min before sacrifice. Similar DDVP pretreatment potentiated the anticholinesterase action of malaoxon (10 mg/kg, ip). Thus, even though DDVP toxicity was not altered by DDT- or dieldrin-induced changes in organophosphate binding, DDVP inhibited malaoxon binding and increased malaoxon toxicity.
D000818:Animals; D001921:Brain / Q000201:enzymology; D002802:Cholinesterases / Q000378:metabolism; D003634:DDT / Q000378:metabolism*; D004006:Dichlorvos / Q000378:metabolism*; D004026:Dieldrin / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology; D008294:Malathion / Q000031:analogs & derivatives* / Q000378:metabolism*; D008297:Male; D051379:Mice; D011485:Protein Binding / Q000187:drug effects
D004006:Dichlorvos; D003634:DDT; D002802:Cholinesterases; D004026:Dieldrin; D008294:Malathion