Abstract
Oral administration of 5 mg/kg body weight of deltamethrin, an a-cyano type II pyrethroid insecticide once a day for 1, 7, 15 and 21 consecutive days to young Druckerey rats (6–8 weeks old) produced a time dependent increase in the activity of cytochrome P450 (P450) dependent 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) in rat brain microsomes. A significant induction was observed on prolonged exposure of deltamethrin for 15 or 21 days. The induction in the activity of cerebral P450 enzymes was associated with the time dependent increase in the spontaneous locomotor activity indicating accumulation of deltamethrin or its metabolites in brain with the increase in the duration of exposure. Administration of deltamethrin (5 mg/kg) for 21 days produced region specific changes in the dealkylation of ethoxyresorufin and pentoxyresorufin in rat brain with significant induction occurring in the activity of P450 1A1/2 dependent EROD in cerebellum, hippocampus, hypothalamus and medulla-pons and that of P450 2B1/2 mediated PROD in hippocampus, hypothalamus, corpus striatum and mid brain. The data suggests that the differences in the induction of individual P450 isoenzymes in diverse brain regions could play a role in regulating the response of brain to pyrethroid insecticides by modulating their concentrationper se or their active metabolites at the target site(s).
Similar content being viewed by others
References
All, M.M., Bawari, M., Misra, U.K. and Babu, G.N. (2000) Locomotor and learning deficits in adult rats exposed to monosodium-L-glutamate during early life.Neurosci. Lett. 284, 57–60.
Anadon, A., Martinez-Larranaga, M.R., Diaz, M.J., Bringas, P. and Fernandiz, M.C. (1991). Effect of deltamethrin on antipyrene pharmacokinetics and metabolism in rats.Arch. Toxicol,65, 156–159.
Anadon, A., Martinez-Larranaga, M.R., Diaz, M.J., Bringas, P., Fernandiz, M.C, Martinez, M.A. and Fernandez-Cruz, M.L. (1995). Effect of flumethrin on hepatic drug metabolizing enzymes and antipyrene disposition in rats.Toxicol. Appl. Pharmacol,132, 14–18.
Anandatheerthavarada, H.K., Shankar, S.K. and Ravin-dranath, V. (1990) Rat brain cytochromes P450: Catalytic, immunochemical properties and inducibility of multiple forms.Brain Res. 536, 339–343.
Anadon, A., Martinez-Larranaga, M.R., Fernandez-Cruz, ML., Diaz, M.J., Fernandez, M.C. and Martinez, M.A. (1996) Toxicokinetics of deltamethrin and 4′-HO-metab-olite in the rat.Toxicol. Appl. Pharmacol. 141, 8–16.
Casida, J.E., Gammon, D.W., Glickman, A.H. and Lawrence, L.J. (1983) Mechanisms of selective action of pyrethroid insecticides.Annu. Rev. Pharmacol. Toxicol. 23, 413–438.
Catinot, R., Hoellinger, H., Sonnier, M., Do C. -T., Pichon, J. and Nguyen, H.N. (1989)In vitro covalent binding of the pyrethroids cismethrin, cypermethrin and deltamethrin to rat liver homogenate and microsomes.Arch. Toxicol. 63, 214–220.
Crofton, K.M. and Reiter, L.W. (1987) Pyrethroid insecticides and the y-aminobutyric acidAreceptor complex: Motor activity and the acoustic startle response.J. Pharmacol. Exp. Ther. 243, 946–954.
Dayal, M., Parmar, D., Dhawan, A., Dwivedi, U.N., Doeh-mer, J. and Seth, P.K. (1999) Induction of rat brain and liver cytochrome P450 1A1/1A2 and 2B1/2B2 isoenzymes by deltamethrin.Environ. Toxicol. Pharmacol. 7, 169–178.
Dhawan, A., Parmar, D., Dayal, M. and Seth, P.K. (1999) Cytochrome P450 (P450) isoenzyme specific dealkyla-tion of alkoxyresorufins in rat brain microsomes.Mol. Cell. Biochem. 200, 169–176.
Elliot, M., Farnham, A.W., Janes, N.F., Needham, P.H. and Pearson, B.C. (1974) 5-Benzyl-3-furylmethyl chrysanthe-mate: A new potent insecticide.Nature (London).213, 493–94.
Elliott, M. (1976) Properties and applications of pyrethroids.Environ. Health Perspect. 14, 3–13.
Glowinski, J. and Iverson, L. (1966) Regional studies of the catecholamines in rat brain.J. Neurochem. 13, 655–669.
Gray, A.J. and Rickard, J. (1982) Toxicity of pyrethroids to rats after direct injection into the central nervous system.Neurotoxicology 3, 25–35.
Hedlund, E., Gustafsson, J.A. and Warner, M. (1998). Cytochrome P450 in the brain: 2 B or not 2B.Trends Pharmacol. Sci.,19, 82–85.
Husain, R., Gupta, A., Khanna, V.K. and Seth, P.K. (1991). Neurotoxicological effects of a pyrethroid formulation, fenvalerate in rats.Res. Commun. Chem. Pathol. Pharmacol.,73, 111–114.
Husain Raghib, Malaviya, M., Seth, P.K. and Husain, R. (1992) Differential responses to brain polyamines following in utero exposure to synthetic pyrethroid insecticides: A preliminary report.Bull. Environ. Contam. Toxicol. 49, 402–409.
Husain, R., Husain, Raghib, Adhami, V.M. and Seth, P.K. (1996) Behavioral, neurochemical and neuromorpholog-ical effects of deltamethrin in adult rats.J Toxicol. Environ. Health. 48, 515–526.
Lawrence, L.J. and Casida, J.E. (1983) Stereospecific action of pyrethroid insecticides on the gamma-aminobutyric acid receptor-ionophore complex.Science 221, 1399–1401.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193, 265–275.
Malaviya, M., Husain, Raghib, Seth, P.K. and Husain, R. (1993) Perinatal effects of two pyrethroid insecticides on brain neurotransmitter function in the neonatal rat.Vet. Human Toxicol. 35, 119–122.
Niznik, H.B., Tyndale, R.F., Salee, F.R., Gonzalez F.J., Hard-wick, J.P., Inaba, T and Kalow, W. (1990) The dopamine transporter and cytochrome P450 IID1 (Debrisoquine 4-hydroxylase) in brain: Resolution and identification of two distinct [3H]GBR-12935 binding proteins.Arch. Biochem. Biophys. 276, 424–433.
Parmar, D., Dhawan, A., Dayal, M. and Seth, P.K. (1998) Immunochemical and biochemical evidences for expression of phenobarbital and 3-methycholanthrene inducible isoenzymes of cytochrome P450 in rat brain.Int. J. Toxicol. 17, 619–630.
Ray, D.E. and Cremer, J.E. (1979) The action of deltamethrin (a synthetic pyrethroid) on the rat.Pestic. Biochem. Physiol. 10, 333–340.
Rickard, J., Brodie, M.E., 1985. Correlation of blood and brain levels of the neurotoxic pyrethroid deltamethrin with the onset of symptoms in rats.Pestic. Biochem. Physiol. 23, 143–156.
Soderlund, D.M. and Casida, J.E. (1977) Effects of pyrethroid structure on rates of hydrolysis and oxidation by mouse liver microsomal enzymes.Pest. Biochem. Physiol. 7, 391–401.
Sheets, L.P., Doherty, J.D., Law, M.W., Reiter, L.W. and Crofton, K.M. (1994) Age dependent differences in the susceptibility of rats to deltamethrin.Toxicol. Appl. Pharmacol. 126, 186–190.
Stapleton, G., Steel, M., Richardson, M., Mason, J.O., Rose, K.A., Morris, R.G.M. and Lathe, R. (1995) A novel cytochrome P450 expressed primarily in brain.J. Biol. Chem. 270, 29739–29745.
Strobel, H.W., Kawashima, H., Geng, J., Sequira, D., Bergh, A., Hodgson, A.V., Wang, H. and Shen S. (1995) Expression of multiple forms of brain cytochrome P450.Expression of multiple forms of brain cytochrome P450 82/83, 639–643.
Tirumalai, P.S., Bhamre, S., Upadhya, S.C., Boyd, M.R. and Ravindranath, V. (1998) Expression of multiple forms of cytochrome P450 and associated monooxygenase activities in rat brain regions.Biochem. Pharmacol. 56, 371–375.
Verschoyle, R.D. and Aldridge, W.N. (1980) Structure-activity relationship of some pyrethroids in rats.Arch. Toxicol. 45, 325–329.
Vijverberg, H.P.M. and Van den Brecken, J. (1990) Neurotoxicological effects and the mode of action of pyrethroid insecticides.CRC Rev. Toxicol. 21, 105–126.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dayal, M., Parmar, D., Ali, M. et al. Induction of rat brain cytochrome P450s (P450s) by deltamethrin: Regional specificity and correlation with neurobehavioral toxicity. neurotox res 3, 351–357 (2001). https://doi.org/10.1007/BF03033196
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF03033196