Glutathione Depletion in Isolated Hepatocytes: Its Relation to Lipid Peroxidation and Cell Damage

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Abstract
The effects of glutathione depletion in isolated hepatocytes were 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 1% 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 well as paracetamol and ethylmorphine, prevented lipid peroxidation and lysis. Glutathione deficiency per se may lead to lipid peroxidation and this reaction might cause the observed hepatocellular lysis.

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