In vitro interactions between organophosporous pesticides and consequences of pre-treatment with nicotine and alcohol on in vitro pesticide metabolism in rats.
Kousba-A; Poet-TS; Zangar-RC; Timchalk-C
Drug Metab Rev 2004 Sep; 36(Suppl 1):536
Chlorpyrifos (CPF) and diazinon (DZN) are structurally and mechanistically similar pesticides, having different rates of metabolism. Their toxicity is mediated through CYP450 metabolism to CPF-oxon and DZN-oxon. Detoxification is also mediated by CYP450s, forming a pyridinol (TCP) and a pyrimidine (IMHP), respectively. Since exposures to pesticides may be complicated by exposure to multiple pesticides and other xenobiotics, the effect of co-incubation of CPF and DZN on the in vitro metabolism of each pesticide was assessed, as was the effect of pre-treating rats with nicotine or ethanol for 5 days. Western blot analysis of several CYP450 proteins indicated no induction as a result of nicotine treatment and a slight induction due to ethanol pre-treatment. Interestingly, co-incubation with two pesticides or pre-treatment with nicotine or ethanol had different effects on bioactivation and detoxification pathways. There was little effect on TCP formation following either pre-treatment, but a potential slight induction of oxon following nicotine pre-treatment. Detoxification of the parent pesticides was inhibited in a competitive manner by co-incubation, whereas bioactivation to the oxons indicated a non-competitive mechanism. Inhibitory rate constants were approximately 5-fold higher for the bioactivation pathways than the detoxification pathways. Metabolic interactions between pesticides and as a result of nicotine or alcohol exposures are potentially very important to the ratio of bioactivation/detoxification of these compounds in vivo.
Pesticides; Pesticides-and-agricultural-chemicals; Pesticide-residues; Pest-control; Insecticides; Insecticide-poisoning; Metabolic-study; Metabolism; Metabolites; Agricultural-chemicals; Agricultural-industry; Agriculture
Battelle, Pacific Northwest Division, 999 Battelle Blvd., Richland WA
Conference/Symposia Proceedings; Abstract
Research Tools and Approaches: Exposure Assessment Methods
Drug Metabolism Reviews
Battelle Memorial Institute, Richland, Washington