title: Downregulation of male-specific cytochrome P450 by profenofos.
abstract: The health hazards of individual organophosphorus insecticides have been characterized by their acute toxicity, mainly by investigating their cholinesterase inhibition. However, the chronic effects of most of these toxicants on the drug-metabolizing enzymes have not been investigated. Profenofos (O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate) is an organophosphorus pesticide widely used in cotton cultivation. In the present study, we investigated the effect of profenofos on male-specific cytochrome P450 (CYP) enzymes in adult Wistar rats. We orally administered 17.8 mg/kg body weight, twice weekly for 65 days. Profenofos downregulated levels of hepatic and testicular CYP2C11 and CYP3A2 mRNA and protein expression. Testicular aromatase (CYP19A) mRNA was decreased in the profenofos-treated rats compared to controls. Overall, the present study suggests that profenofos acts as an endocrine disruptor of male-specific CYP enzymes and affects testosterone concentration, which implicates its deleterious effects on animal or human males chronically exposed to organophosphorus pesticide.
authors.affiliation: Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Gihan G
authors.initials: GG
authors.lastname: Moustafa
authors.forename: Zein S
authors.initials: ZS
authors.lastname: Ibrahim
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: Mervat H
authors.initials: MH
authors.lastname: Ghoneim
authors.forename: Kentaro Q
authors.initials: KQ
authors.lastname: Sakamoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fujita
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D063086:Organothiophosphates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013737:Testis / Q000187:drug effects / Q000201:enzymology
chemical_list: D047072:Aromatase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D007306:Insecticides; D063086:Organothiophosphates; D012333:RNA, Messenger; C024273:profenofos; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase