Dichloroacetate- and Trichloroacetate-Induced Cellular Death and Oxidative Stress in AML-12 Hepatocytes.

摘要

The water chlorination process results in the production of different haloacetates that have been found to be toxic. Previous in vivo studies in animals have reported several effects, including hepatotoxicity, carcinogenicity and induction of oxidative stress by two important haloacetates produced during this process, dichloroacetate (DCA) and trichloroacetate (TCA). This study focused on AML-12 hepatocyte cytotoxicity and induction of oxidative stress resulting from exposure to DCA and TCA, in an effort to establish an in vitro system to test the effects of these and other haloacetates, as well as mixtures of haloacetates.;Cell cultures were exposed separately to varying DCA and TCA concentrations and incubated for 24, 48, and 72 hours. Cellular toxicity was assessed by determining cellular viability, and oxidative stress was assessed by three biomarkers, including superoxide anion (SA) and lipid peroxidation (LP) production, and superoxide dismutase (SOD) activity. The results of the study demonstrate concentration- and time-dependent effects on the production of cellular death and various biomarkers of oxidative stress by DCA and TCA, similar to what is observed in vivo, after long term exposure. The results also demonstrate that the effective concentrations of the compounds are exactly a factor of ten times greater than the doses required for the production of various levels of hepatotoxic and hepatocarcinogenic, as well as biomarkers of oxidative stress in animals, and suggest the cells to be an appropriate model for testing the effects of various individual haloacetates, and mixtures of haloacetates.