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Abstract

Involvement of calcium and iron in Quin 2 toxicity to isolated hepatocytes.

L Carpenter-Deyo and D J Reed
Journal of Pharmacology and Experimental Therapeutics August 1991, 258 (2) 747-752;
L Carpenter-Deyo
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D J Reed
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Abstract

When treated with the cytosolic Ca++ indicator Quin 2-acetoxymethyl ester (Quin 2-AM), isolated hepatocytes exhibited signs of toxicity, such as extensive lipid peroxidation and vitamin E loss and release of lactate dehydrogenase. Lipid peroxidation induced by this agent was blocked completely by cotreatment of the cells with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, EDTA, ruthenium red, carbonyl cyanide m-chlorophenylhydrazone, desferal and trifluoperazine, and was partially inhibited by quinacrine and indomethacin. With the exception of carbonyl cyanide m-chlorophenylhydrazone and quinacrine, these agents also inhibited lactate dehydrogenase leakage. Although the results with ruthenium red suggested that Quin 2-AM may cause toxicity by altering handling of Ca++ by mitochondria, mitochondrial membrane potential was not altered in cells treated with Quin 2-AM until after toxicity occurred. Evidence of a direct, potentiative effect of Quin 2 on iron-induced lipid peroxidation was gained from experiments with liposomes. Treatment of cells with Quin 2-AM did not enhance nitro blue tetrazolium reduction, suggesting that Quin 2 did not stimulate O2- production by the cells. Direct chelation of Ca++ did not appear to be involved in the mechanism of Quin 2 toxicity, for an analog of Quin 2 that is virtually nonhydrolyzable, which greatly limits the binding of Ca++, also caused lipid peroxidation and cell death. These results suggest that Quin 2 causes toxicity by chelating iron or by activating some cellular process(es) that is dependent on the presence of iron or Ca++.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 258, Issue 2
1 Aug 1991
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Abstract

Involvement of calcium and iron in Quin 2 toxicity to isolated hepatocytes.

L Carpenter-Deyo and D J Reed
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 747-752;

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Abstract

Involvement of calcium and iron in Quin 2 toxicity to isolated hepatocytes.

L Carpenter-Deyo and D J Reed
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 747-752;
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