Al-Abbasi Fahad A
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
Toxicol Ind Health. 2016 Aug;32(8):1478-1485. doi: 10.1177/0748233714567184. Epub 2015 Jan 22.
Dibromoacetonitrile (DBAN) is a disinfection by-product classified as a potential human and animal carcinogen. This study aimed at investigating the ability of myeloperoxidase (MPO) to oxidize DBAN to cyanide (CN) in vitro Detection of CN served as a marker for the possible generation of free radical intermediates implicated in DBAN-induced toxicity. Optimum conditions for the oxidation of DBAN to CN were characterized with respect to pH, temperature, and time of incubation as well as DBAN, MPO, potassium chloride, and hydrogen peroxide (HO) concentrations in incubation mixtures. Maximum reaction velocity and Michaelis-Menten constant were assessed. Addition of sodium hypochlorite to the reaction mixtures significantly enhanced the rate of the reaction. Addition of the MPO inhibitors, sodium azide, 4-amino benzoic acid hydrazine, or indomethacin to the reaction mixtures significantly decreased the rate of DBAN oxidation. Inclusion of the antioxidant enzyme superoxide dismutase in the incubation mixtures significantly decreased the rate of reaction. Inclusion of the sulfhydryl compounds as reduced glutathione, N-acetylcysteine, d-penicillamine, or l-cysteine enhanced the rate of DBAN oxidation. These results demonstrate the ability of MPO/HO/chloride ion system to oxidize DBAN to CN and provide insight for the elucidation of DBAN chronic toxicity.
二溴乙腈（DBAN）是一种消毒副产物，被归类为潜在的人类和动物致癌物。本研究旨在调查髓过氧化物酶（MPO）在体外将DBAN氧化为氰化物（CN）的能力。检测CN作为可能产生与DBAN诱导毒性有关的自由基中间体的标志物。针对pH、温度、孵育时间以及孵育混合物中DBAN、MPO、氯化钾和过氧化氢（HO）的浓度，对DBAN氧化为CN的最佳条件进行了表征。评估了最大反应速度和米氏常数。向反应混合物中添加次氯酸钠显著提高了反应速率。向反应混合物中添加MPO抑制剂叠氮化钠、4-氨基苯甲酸肼或吲哚美辛显著降低了DBAN氧化速率。在孵育混合物中加入抗氧化酶超氧化物歧化酶显著降低了反应速率。加入还原型谷胱甘肽、N-乙酰半胱氨酸、d-青霉胺或l-半胱氨酸等巯基化合物提高了DBAN氧化速率。这些结果证明了MPO/HO/氯离子系统将DBAN氧化为CN的能力，并为阐明DBAN的慢性毒性提供了见解。
