Metabolism of toxic substances in isolated hepatocytes

Chloroform and selenite toxicity have been studied in isolated hepatocytes. Two different toxic mechanisms, which lead to cellular lysis after distinct lag periods, are compared. Chloroform toxicity can be divided into 2 phases, a first phase characterized by chloroform metabolism and a second phase characterized by lipid peroxidation. GSH depletion during the first phase is claimed to be a prerequisite for lipid peroxidation in the second phase. Selenite metabolism leads to cofactor depletion as well. Selenite reduction via a GSH reductase dependent pathway exhausts the cells of NADPH and this effect can be related to cellular lysis.