title: In-vitro testicular bioactivation of acrylonitrile.
abstract: The present work examines the mechanism of testicular toxicity of acrylonitrile. In testicular centrifugal fractions from Sprague Dawley rats, the metabolism of VCN to cyanide (CN-) was highest in the microsomal fraction and required NADPH for maximum activity. This biotransformation of VCN to CN- was characterized with respect to time (30 min), microsomal protein concentration (1.5 mg ml(-1)), pH (7.5) and temperature (37 degrees C). The V(max) of the reaction was 65.1 pmol CN- mg protein(-1) min(-1) and K(m) was 88.6 micromol VCN. Flushing the microsomes with carbon monoxide (CO)(4:1, CO/O2 v/v), addition of benzimidazole (1 mM) or addition of SKF 525-A (5x10(-4) M) to incubation mixtures significantly inhibited VCN metabolism by 49%, 54% and 37.4% respectively. Activation of VCN to CN- was markedly increased in microsomes obtained from phenobarbital (PB)-treated rats (128.2%). Addition of glutathione (GSH), L-cysteine, D-penicillamine or 2-mercaptoethanol significantly enhanced the release of CN- from VCN 126%, 247%, 202% and 129% of the control value respectively. These findings indicate that VCN is metabolized in the testis via cytochrome P-450 dependent mixed function oxidase system.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
authors.forename: A H
authors.initials: AH
authors.lastname: Abdel-Aziz
authors.forename: A B
authors.initials: AB
authors.lastname: Abdel-Naim
authors.forename: F M
authors.initials: FM
authors.lastname: Hamada
authors.forename: A E
authors.initials: AE
authors.lastname: Ahmed
mesh_terms: D000181:Acrylonitrile / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism; D013737:Testis / Q000378:metabolism*
chemical_list: D009249:NADP; D000181:Acrylonitrile