Effect of prenatal exposure of deltamethrin on the ontogeny of xenobiotic metabolizing cytochrome P450s in the brain and liver of offsprings.
Prenatal exposure to low doses (0.25 or 0.5 or 1.0 mg/kg, p.o.) of deltamethrin, a type II pyrethroid insecticide, to pregnant dams from gestation days 5 to 21 (GD5-21) produced dose-dependent alterations in the ontogeny of xenobiotic metabolizing cytochrome P450 (CYP) isoforms in brain and liver of the offsprings. RT-PCR analysis revealed dose-dependent increase in the mRNA expression of cerebral and hepatic CYP1A1, 1A2, 2B1, 2B2, and 2E1 isoenzymes in the offsprings exposed prenatally to deltamethrin. Similar increase in the activity of the marker enzymes of these CYP isoforms has indicated that placental transfer of the pyrethroid, a mixed type of CYP inducer, even at these low doses may be sufficient to induce the CYPs in brain and liver of the offsprings. Our data have further revealed persistence in the increase in expression of xenobiotics metabolizing CYPs up to adulthood in brain and liver of the exposed offsprings, suggesting the potential of deltamethrin to imprint the expression of CYPs in brain and liver of the offsprings following its in utero exposure. Furthermore, though the levels of CYPs were several fold lower in brain, almost equal magnitude of induction in cerebral and hepatic CYPs has further suggested that brain CYPs are responsive to the induction by environmental chemicals. The present data indicating alterations in the expression of xenobiotic metabolizing CYPs during development following prenatal exposure to deltamethrin may be of significance as these CYP enzymes are not only involved in the neurobehavioral toxicity of deltamethrin but have a role in regulating the levels of ligands that modulate growth, differentiation, and neuroendocrine functions.
Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow-226 001, U.P., India.
Ashu
A
Johri
Alok
A
Dhawan
Ram
R
Lakhan Singh
Devendra
D
Parmar
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008658:Inactivation, Metabolic; D007527:Isoenzymes; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009570:Nitriles / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000201:enzymology*; D011722:Pyrethrins / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity*
D007527:Isoenzymes; D009570:Nitriles; D011722:Pyrethrins; D015262:Xenobiotics; C017180:decamethrin; D003577:Cytochrome P-450 Enzyme System