In vitro activation of dibromoacetonitrile to cyanide: role of xanthine oxidase.
Dibromoacetonitrile (DBAN) is a disinfection byproduct of chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. The present work provides evidence for DBAN activation to cyanide (CN(-)) by the hypoxanthine (HX)/xanthine oxidase (XO)/iron (Fe) system in vitro. Optimum conditions for the oxidation of DBAN to CN(-)were characterized. Addition of the sulfhydryl compounds glutathione, N-acetyl- L-cysteine or dithiothreitol significantly enhanced the rate of CN(-)release. A high positive correlation existed between hydroxyl free radical ((*)OH) generation and CN(-) formation. Addition of the (*)OH scavengers mannitol or dimethylthiourea to the reaction mixtures resulted in a significant decrease in the rate of DBAN oxidation. Addition of the antioxidant enzymes catalase or superoxide dismutase resulted in a significant decrease in the rate of DBAN oxidation. The iron chelator desferrioxamine significantly decreased CN(-) formation. The maximum velocity (V(max)) and Michaelis-Menten constant (K(m)) of the reaction were assessed. Allopurinol competitively inhibited the reaction, while folic acid uncompetitively inhibited the reaction. In conclusion, (*)OH generated by the HX/XO/Fe system are implicated in DBAN oxidation. The present results represent a novel pathway for DBAN activation and might be important in explaining DBAN-induced toxicity.
Mohamadin
Ahmed M
AM
Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Abdel-Naim
Ashraf B
AB
D000097:Acetonitriles / Q000378:metabolism*; D000111:Acetylcysteine / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003486:Cyanides / Q000378:metabolism*; D003676:Deferoxamine / Q000378:metabolism; D004203:Disinfection; D004229:Dithiothreitol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019271:Hypoxanthine / Q000378:metabolism; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D000097:Acetonitriles; D003486:Cyanides; D016166:Free Radical Scavengers; D014874:Water Pollutants, Chemical; D019271:Hypoxanthine; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005978:Glutathione; D003676:Deferoxamine; D004229:Dithiothreitol; C051715:dibromoacetonitrile; D000111:Acetylcysteine