Effect of pretreatment of cytochrome P450 (P450) modifiers on neurobehavioral toxicity induced by deltamethrin

• Published in: Food and chemical toxicology 2003-03, Vol.41 (3), p.431-437
• Main Authors: Dayal, M, Parmar, D, Dhawan, A, Ali, M, Dwivedi, U.N, Seth, P.K
• Format: Article
• Language: English
• Subjects: 3-methylcholanthrene; Animals; Biological and medical sciences; cobalt; Cobalt - pharmacology; cobalt chloride; cytochrome P-450; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - metabolism; deltamethrin; environmental exposure; enzyme activity; Enzyme Induction - drug effects; Enzyme Inhibitors - pharmacology; Insecticides - toxicity; Male; Medical sciences; Methylcholanthrene - pharmacology; Motor Activity - drug effects; Nervous System Diseases - chemically induced; neurotoxicity; Neurotoxins - toxicity; Nitriles; oral administration; Pesticides, fertilizers and other agrochemicals toxicology; pharmacokinetics; phenobarbital; Phenobarbital - pharmacology; Pyrethrins - toxicity; Rats; Rats, Wistar; toxicity testing; Toxicology; Tremor - chemically induced
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/S0278-6915(02)00249-1

To investigate the involvement of cytochrome P450 (P450) enzyme induction and the effect of different P450 modifiers in the neurobehavioral toxicity of deltamethrin, deltamethrin (10 mg/kg; orally for 1 day) was administered to young male albino Wistar rats, or in rats pretreated with phenobarbital (PB; 80 mg/kg, ip for 5 days), an inducer of P450 2B1/2B2 or 3-methylcholanthrene (MC; 30 mg/kg, ip for 5 days), an inducer of P450 1A1/1A2 or cobalt chloride (CoCl(2); sc for 2 days), a depletor of P450s. The administration of PB or MC or CoCl(2) alone did not produced any symptoms of neurobehavioral toxicity. While a single oral administration of deltamethrin produced tremors in two out of 10 rats and decreased the spontaneous locomotor activity, pretreatment with MC or PB potentiated the deltamethrin induced neurobehavioral toxicity with 50% of the treated rats exhibiting tremors. Half of the animals pretreated with MC prior to exposure to deltamethrin also exhibited choreoathetosis. The decrease in the spontaneous locomotor activity was found to be much more significant in PB- or MC-pretreated animals exposed to deltamethrin. In contrast to the pretreatment with inducers, rats pretreated with CoCl(2) exhibited no symptoms of tremors or choreoathetosis, indicating that a reactive metabolite of deltamethrin is formed by P450 catalysed reactions which is involved in the neurobehavioral toxicity of deltamethrin.