A Search For Cellular and Molecular Mechanisms Involved in Chromate (CrVI) Toxicity

In this study we have investigated the cytotoxic mechanisms of arsenite As(III) inisolated rat hepatocytes. Our experimental design was based on Accelerated CytotoxicMechanisms Screening technique (ACMS) using the LC502hr concentration, 50 µM. Arsenitecytotoxicity was associated with little oxidative stress and lysosomal damage did not occur.However arsenite cytotoxicity was associated with loss of mitochondrial membrane potential,which was inhibited by the ATP generators fructose, xylitol and glutamine; and also by MPTpore sealing agents such as carnitine, cyclosporin and trifluoperazine.in Arsenite inducedcytotoxicity, mitochondrial membrane potential decline and also ROS formation weresignificantly increased by inactivating hepatocyte methionine synthase or hepatocyte methyltransferase but were prevented by methyl donors such as betaine, methionine, folic acid andmethylcobalamine and this suggests that arsenite is detoxified by reductive methylation. Theactivity of caspase-3 enzyme the main mediator of apoptosis, was also significantly increased,following incubation of hepatocytes with different concentrations of arsenite. In conclusionarsenite induced cytotoxicity could be attributed to mitochondrial toxicity and ATP depletion.