Mechanisms of hepatotoxicity of chloroacetonitrile - an end product of water chlorination

• Published in: Pakistan journal of pharmaceutical sciences 2013-01, Vol.26 (1), p.145
• Main Authors: Abo-Salem, Osama Mohamed, Ghonaim, Mabrouk Mahmoud, Al-Zahrani, Saad Salem
• Format: Article
• Language: English
• Subjects: Acetonitrile; Acetonitriles - toxicity; Animals; Bilirubin - blood; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical properties; Chlorination; Composition; Cytokines - blood; Disinfection and disinfectants; Dose-Response Relationship, Drug; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Glutathione Transferase - metabolism; Identification and classification; Inflammation Mediators - blood; Liver - drug effects; Liver - immunology; Liver - metabolism; Liver - pathology; Liver Function Tests; Male; Malondialdehyde - metabolism; Oxidative Stress - drug effects; Rats; Rats, Wistar; Superoxide Dismutase - metabolism; Time Factors; Transaminases - blood; Water chemistry; Water Pollutants, Chemical - toxicity; Water Purification
• ISSN: 1011-601X

Chloroacetonitrile is a disinfectant by-product of chlorination of drinking water and is considered as a direct-acting mutagenic and carcinogenic agent. Time-course and dose-response studies were performed to examine the mechanism of chloroacetonitrile-induced hepatotoxicity. In the time-course study, animals were scarified at 2, 4, 6 and 12 h after a single oral dose of chloroacetonitrile (38 mg/kg, p.o.). In the dose-response study, rats were scarified at 2 h after a single oral dose of chloroacetonitrile (9, 19, 38, and 76 mg/kg). In the time-course study chloroacetonitrile induced a significant decrease of hepatic glutathione, and activities of glutathione-S-transferase, glutathione proxidase and superoxide dismutase accompanied with an increase of hepatic malondialdehyde, plasma cytokines (IL-6 & 10 and TNF-α), serum aminotransferases and total bilirubin after 2 h of administration. Maximal alteration of the estimated parameters was observed at 4 h and returned to normal value at 6 h and/or 12 h after chloroacetonitrile treatment. Moreover, the alterations in oxidant, antioxidant parameters, inflammatory cytokines and the liver function tests were dose dependant. Histopathological findings supported the biochemical results. These data indicate that the mechanism of chloroacetonitrile-induced hepatotoxicity may be mediated through depletion of antioxidants, induction of oxidative stress and inflammatory cytokines.