Abstract
Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. The present work provides an evidence for CAN activation to cyanide (CN
−) by myeloperoxidase (MPO)/hydrogen peroxide (H
2O
2)/chloride (Cl
−) system in vitro. Optimum conditions for the oxidation of CAN to CN
− were characterized with respect to pH, temperature and time of incubation as well as CAN, MPO, H
2O
2 and KCl concentrations in incubation mixtures. The kinetic parameters governing the reaction; maximum velocity (
V
max) and Michaelis–Menten constant (
K
m) were assessed. Oxidation of CAN to CN
− by NaOCl alone was shown. Addition of the MPO inhibitors; sodium azide (NaN
3), 4-amino benzoic acid hydrazine (ABAH) or indomethacin to the reaction mixtures resulted in a significant decrease in the rate of CAN oxidation. Inclusion of the antioxidant enzyme catalase (CAT) in the incubation mixtures resulted in a significant decrease in the rate of CAN oxidation and CN
− formation. Addition of the sulfhydryl compounds; glutathione (GSH),
N-acetyl-
l-cysteine (NAC),
l-cysteine or
d-penicillamine significantly enhanced the rate of CN
− release. In conclusion, MPO/H
2O
2/Cl
− system has the ability of oxidizing CAN to CN
−. The present results represent a novel pathway for CAN activation and might be important in explaining CAN-induced toxicity.