| 8615874 |
O'Shaughnessy JA, Sultatos LG: Interaction of ethanol and the organophosphorus insecticide parathion. . Biochem Pharmacol. 1995 Nov 27;50(11):1925-32.
Phosphorothioate insecticides such as parathion (O,O-diethyl-O-p-nitrophenyl phosphorothioate) undergo P450-dependent oxidative desulfuration, leading to both activation and detoxification of these compounds. Consequently, alterations in P450-dependent oxidative desulfuration may affect the acute toxicities of these insecticides. In the present study, pretreatment of mice with 15% ethanol in the drinking water for 6 days antagonized the acute toxicity of parathion, but not its toxic metabolite paraoxon (O,O-diethyl-O-p-nitrophenyl phosphate), suggesting that ethanol affected the oxidative desulfuration of this insecticide. The presence of ethanol within hepatic microsomal incubations did not alter the P450-dependent formation of paraoxon (activation) and p-nitrophenol (detoxification), although p-nitrophenol levels were increased in the presence of ethanol as a result of inhibition of its biotransformation to 4-nitrocatechol by CYP2E1. Ethanol exposure reduced hepatic pyruvate levels, but had no effect on levels of lactate, isocitrate, alpha-ketoglutarate, and malate. Calculation of cytosolic NAD+/NADH and cytosolic NADP+/NADPH redox ratios did not reveal any detectable difference in redox state between control and ethanol-treated mice. Since ethanol did not alter directly the P450-dependent activation or detoxification of parathion, and did not decrease NADPH levels, ethanol's antagonism of the acute toxicity of parathion may result from reduced availability of O2. |
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