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Toxicity to isolated hepatocytes caused by the intracellular calcium indicator, Quin 2

L Carpenter-Deyo, JR Duimstra, O Hedstrom and DJ Reed

Department of Biochemistry and Biophysics, Oregon State University, Corvallis.

To determine whether incubation for several hours with intracellular Ca++ indicators caused toxicity to freshly isolated hepatocytes from rats, cells were incubated under 95% O2-5% CO2 in medium containing 2 mM Ca++ and the acetoxymethyl (AM) esters of Quin 2, Indo 1, Fluo 3, 5,5'-Dimethyl BAPTA, 4,4'-Difluoro BAPTA or Fura 2 for up to 5 hr. Quin 2-AM and Indo 1-AM (2.5 microM) induced lipid peroxidation in the cells after 1 or 3 hr of treatment, respectively. Additional experiments with Quin 2-AM (25 microM) revealed that it also caused lactate dehydrogenase leakage, cell blebbing and vitamin E loss in cells, but did not affect reduced glutathione or intracellular Ca++ content. The ability of Quin 2-AM to cause toxicity was dependent on the amount of Quin 2 which was present in the cell. Ca++ appeared to be involved in the mechanism of Quin 2-AM toxicity, for modulation of the extracellular Ca++ concentration partially inhibited lipid peroxidation, vitamin E loss, cell blebbing and lactate dehydrogenase leakage.

Volume 258, Issue 2, pp. 739-746, 08/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics.