In-vitro testicular bioactivation of acrylonitrile.
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.
Abdel-Aziz
A H
AH
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Abdel-Naim
A B
AB
Hamada
F M
FM
Ahmed
A E
AE
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*
D009249:NADP; D000181:Acrylonitrile