Long lasting effects of prenatal exposure to deltamethrin on cerebral and hepatic cytochrome P450s and behavioral activity in rat offspring

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Abstract

Prenatal exposure to different doses (0.25, or 0.5 or 1.0 mg/kg corresponding to 1/320th or 1/160th or 1/80th of LD50) of deltamethrin to the pregnant Wistar rats from gestation day 5 to 21 were found to produce a dose dependent increase in the activity of cytochrome P450 (CYP) dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of cytochrome P450 monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have indicated that increase in cytochrome P450 activity may lead to the accumulation of deltamethrin and its metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic cytochrome P450s was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.5 and 1.0 mg/kg) of deltamethrin and up to 9 weeks at the highest dose (1.0 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6 weeks of age, have further indicated that due to the reduced activity of the cytochrome P450s during the ontogeny, the pyrethroid or its metabolites accumulating in the brain may not be cleared from the brain, thereby leading to the persistence in the increase in the expression of cerebral and hepatic cytochrome P450s in the offspring postnatally up to 9 weeks. The data suggests that low dose prenatal exposure to pyrethroids has the potential to produce long lasting effects on the expression of xenobiotic metabolizing cytochrome P450s in brain and liver of the offspring.

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