Cellular toxicity and lipid peroxidation in response to mercury
Stacey, N.H.; Kappus, H.
Toxicology and Applied Pharmacology 63(1): 29-35
1982
ISSN/ISBN: 0041-008X PMID: 7071871 Document Number: 187450
The peroxidation of lipids may account for the toxicity of Hg. Recent evidence has discounted a similar theory for another heavy metal, Cd, when examined in isolated rat hepatocytes. Such a system provides the opportunity to examine several parameters and treatments simultaneously on aliquots from the same parent population of hepatocytes. Isolated hepatocytes were incubated with HgCl2 10-200 .mu.M for 20, 40 or 60 min of incubation. Lipid peroxidation with the concentration of HgCl2 and incubation time, as assessed by increases in thiobarbituric acid-reacting substances and in ethane in the gas phase of the flasks. Cell viability was reduced by Hg2+ as determined by the release of cytoplasmic lactate dehydrogenase from hepatocytes. Reduced glutathione also declined in the presence of the higher concentrations of Hg2+, suggesting this decrease to be a manifestation of the toxic response. The increases in thiobarbituric acid reactant concentrations were closely related to loss of cytoplasmic lactate dehydrogenase, suggesting a possible causative role for lipid peroxidation in the toxic response. Addition of the antioxidant N, N'-diphenyl-p-phenylenediamine or (+)-cyanidanol-3 to the cell suspensions inhibited lipid peroxidation, but only (+)-cyanidanol-3 partially reduced the Hg2+-induced cytotoxicity. The lipid peroxidation associated with loss of viability of isolated rat hepatocytes was not directly responsible for this cell injury.