| 10433881 |
Mostafa AM, Abdel-Naim AB, Abo-Salem O, Abdel-Aziz AH, Hamada FM: Renal metabolism of acrylonitrile to cyanide: in vitro studies. Pharmacol Res. 1999 Aug;40(2):195-200.
Acrylonitrile (VCN) is a widely used industrial chemical. The present work examines the mechanism of its renal toxicity. In renal centrifugal fractions from Sprague-Dawley rats, the metabolism of VCN to cyanide (CN (-)) was highest in the microsomal fraction and required a NADPH-generating system in the presence of magnesium ions for maximum activity. This biotransformation of VCN to CN (-) was characterised with respect to time (15 min), microsomal protein concentration (3 mg ml (-1)), pH (7.5) and temperature (37 degrees C). The V (max) of the reaction was 118.2 pmol CN (-) mg (-1) protein min (-1) and K (m) was 160.2 micromol VCN. Activation of VCN to CN (-) was markedly increased in microsomes obtained from phenobarbital (PB), ethanol, 4-methylpyrazole and 3-methylcholanthrene-treated rats by 161.5, 89.6, 71.0 and 50.2%, respectively. Addition of SKF 525-A (5x10 (-4) m) or benzimidazole (2 m m) to the incubation mixtures significantly inhibited VCN metabolism by 66.6 and 78.8%, respectively. VCN metabolism to CN (-) was enhanced significantly by the addition of 10 m m of glutathione (GSH), l -cysteine, d -penicillamine, cysteamine or 2-mercaptoethanol to 389.5, 886.5, 611. 1, 145.5 and 384.0% of control, respectively. These findings indicate that VCN is metabolised in the kidney via cytochrome P-450-dependent mixed function oxidase system. 1999 Academic Press. |
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