Role of extracellular Ca2+ in toxic liver injury: comparative studies with the perfused rat liver and isolated hepatocytes.
The role of extracellular Ca2+ in toxic liver injury was examined in two in vitro models of the rat liver, the isolated perfused liver and isolated hepatocytes. The toxins t-butylhydroperoxide and carbon tetrachloride, as well as the Ca2+ ionophore, heptafluorodimethyloctanedione (FOD), were employed to induce cellular injury and death. Lipid peroxidation was also measured as the formation of thiobarbituric acid-reactive products. Cell death was measured by the release of lactate dehydrogenase in the perfused liver model and by the uptake of trypan blue in isolated hepatocytes. Toxin-induced cellular injury and death occurred in both in vitro models in the presence and absence of extracellular Ca2+, indicating that an influx of Ca2+ was not essential for toxic liver injury. The degree of toxicity seen in the perfused liver model was independent of increases or decreases in the total calcium concentration present in the liver tissue, providing further evidence that cell death is not dictated solely by changes in cellular calcium content. Isolated hepatocytes differed from the perfused liver, however, undergoing more lipid peroxidation and toxin-induced cell death when incubated in the absence of extracellular Ca2+ than in its presence. While suggesting that extracellular Ca2+ concentrations may have some influence on the expression of toxicity, these results demonstrate the nonessential role extracellular Ca2+ plays in the events leading to toxic liver injury.
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival; D056486:Chemical and Drug Induced Liver Injury; D004347:Drug Interactions; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism* / Q000503:physiopathology; D008274:Magnesium / Q000633:toxicity; D008297:Male; D009336:Necrosis; D010545:Peroxides / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013054:Spectrophotometry, Atomic; D020122:tert-Butylhydroperoxide
D008054:Lipid Peroxides; D010545:Peroxides; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D008274:Magnesium; D002118:Calcium