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.
References
Oct 1, 1979·Biochemical Pharmacology·A R BuckpittJ R Mitchell
Dec 1, 1992·Bulletin of Environmental Contamination and Toxicology·D CovaA Santagostino
Sep 1, 1992·Trends in Pharmacological Sciences·F J Gonzalez
Jan 1, 1992·Journal of Biochemical Toxicology·A E AhmedA M Nour-al Deen
Apr 1, 1992·Scandinavian Journal of Work, Environment & Health·L G SolionovaJ V Plotnikov
Jan 1, 1991·Archives of Biochemistry and Biophysics·D W Rosenberg
Mar 23, 1990·Journal of Chromatography·G D ByrdM F Borgerding
Jul 1, 1990·The Analyst·R RubioG Rauret
Sep 1, 1990·Biomaterials·S Parker, M Braden
Jan 1, 1990·Journal of Biochemical Toxicology·M Y FarooquiR Cavazos
Aug 1, 1990·Archives of Biochemistry and Biophysics·M TamuraM Takeshita
Nov 1, 1989·Chemical Research in Toxicology·D E Feierman, A I Cederbaum
Oct 1, 1988·Journal of Occupational Medicine. : Official Publication of the Industrial Medical Association·J L ChenS Pell
Jul 1, 1988·Toxicology Letters·R TandonS P Srivastava
Jan 1, 1985·Critical Reviews in Toxicology·F P Guengerich, D C Liebler
Dec 1, 1983·Chemico-biological Interactions·M Y Farooqui, A E Ahmed
Feb 1, 1981·Toxicology Letters·M Duverger-Van BogaertM Mercier
Dec 14, 1993·Biochemical Pharmacology·A MadanM D Faiman
Jan 1, 1993·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·R A WardH J Gurland
Jan 1, 1993·Food Additives and Contaminants·H B ConacherJ J Ryan
Apr 1, 1993·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·A M SaillenfaitJ de Ceaurriz