Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and cell damage

The effects of glutathione depletion in isolated hepatocytes have been studied. A list of compounds which depleted glutathione and induced lipid peroxidation and cell lysis is given. The effects of halogenated acetamides were studied in more detail and results of studies on the interaction of iodoacetamide with cellular constituents are presented. A single metabolite of iodoacetamide, tentatively identified as the glutathione conjugate, was excreted from the cells while less than one percent of the "parent compound" was retained, tightly bound to macromolecules. This bound component could not be associated with the cellular damage. Methionine, cysteine and alpha-tocopherol, as wellas paracetamol and ethylmorphine, were found to prevent lipid peroxidation and lysis. It is concluded that GSH deficiency per se can lead to lipid peroxidation and that this reaction caused the observed hepatocellular lysis.