Chloroacetonitrile-Induced Cytotoxicity and Oxidative Stress in Isolated Rat Hepatocytes

Chloroacetonitrile (CAN) is a disinfectant by-product of drinking water chlorination. The present work was designed to investigate the cytotoxic effects as well as the oxidative stress induced by CAN in isolated rat hepatocytes. Hepatocytes were exposed to different concentrations of CAN (5–40 μM) in a time-course experiment for up to 2 h. CAN exposure induced a significant decrease in cell viability and a significant increase in the leakage of hepatic enzymes in a concentration and time-related manner. In addition, CAN exposure results in a significant decrease in cellular GSH content as well as a significant enhancement of TBARS accumulation in a concentration and time-related manners. Also, a subsequent experiment was designed to evaluate the role of GSH modulation and oxidative stress in CAN toxicity in hepatocytes at 2 h. Pretreatment with the GSH-depleting agents enhanced the cytotoxicity of CAN. Conversely, pretreatment with GSH or sulfhydryl compounds attenuated CAN toxicity. Similarly, co-incubation with enzymatic antioxidants, or iron chelator, or hydroxyl radical scavengers exhibited significant protection against CAN cytotoxicity. In conclusion, our results suggest that CAN has a potential cytotoxic effect in isolated rat hepatocytes; and GSH modulation can play a critical role against CAN-induced cellular damage. [Osama S. El-Tawil, Ali H. Abou-Hadeed, Abeir A. Shalaby and Samar M. Mouneir. Chloroacetonitrile-Induced Cytotoxicity and Oxidative Stress in Isolated Rat Hepatocytes. Journal of American Science 2010;6(10):1307-1316]. (ISSN: 1545-1003).