Differential Effect of Ca2+on Oxidant-Induced Lethal Cell Injury and Alterations of Membrane Functional Integrity in Renal Cortical Slices

• Published in: Toxicology and applied pharmacology 1996-12, Vol.141 (2), p.607-616
• Main Authors: Kim, Yong Keun, Kim, Young Hee
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - physiology; Chemical and industrial products toxicology. Toxic occupational diseases; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Glutathione - physiology; Hydrogen Peroxide - toxicity; In Vitro Techniques; Kidney Cortex - drug effects; Kidney Cortex - metabolism; L-Lactate Dehydrogenase - secretion; Lipid Peroxidation - drug effects; Male; Medical sciences; p-Aminohippuric Acid - pharmacokinetics; Peroxides - toxicity; Rabbits; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; tert-Butylhydroperoxide; Tetraethylammonium Compounds - pharmacokinetics; Toxicology; Various organic compounds
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1996.0327

This study was undertaken to examine if modulations of intracellular and extracellular Ca2+affect the lethal cell injury and impairment of membrane transport function induced by oxidants in rabbit renal cortical slices. The oxidantt-butylhydroperoxide (t-BHP) and H2O2increased lactate dehydrogenase (LDH) release and inhibited PAH uptake in a dose-dependent manner, but the potency of H2O2was 100 times lower than that oft-BHP. Catalase prevented the effect of H2O2but not that oft-BHP, suggesting that lower potency of H2O2is attributed to the endogenous catalase activity.t-BHP induced lipid peroxidation and inhibited microsomal Na+-K+-ATPase activity. Omission of Ca2+from the medium or addition of Ca2+channel blockers (verapamil, diltiazem, and nifedipine) prevented the oxidant-induced LDH release. Similar effect was observed by addition of La3+. Buffering intracellular Ca2+with BAPTA/AM decreased the oxidant-induced LDH release. However, the oxidant-induced impairment in PAH uptake was not altered under the same conditions. Also, the inhibition of microsomal Na+-K+-ATPase activity byt-BHP was not affected by verapamil, La3+, and BAPTA/AM. Dithiothreitol and glutathione prevented the oxidant-induced LDH release and reduction of PAH uptake and impeded the oxidant-induced inhibition of Na+-K+-ATPase activity and lipid peroxidation. Effects oft-BHP on TEA uptake were similar to those on PAH uptake. Modulations of intracellular or extracellular Ca2+had little effect on the oxidant-induced lipid peroxidation. Glycine did not exert protective effect against the oxidant-induced cell injury. These results suggest strongly that Ca2+plays an important role in the oxidant-induced LDH release but not in the oxidant-induced alterations of membrane transport function in rabbit renal cortical slices. The role of Ca2+in oxidant-induced LDH release is not apparently associated with peroxidation of membrane lipid.