Protective effects of calcium antagonist (nitrendipine) on calcium ionophore A23187-induced liver cell injury.
Calcium ionophore A23187-induced liver damage was studied in perfused rat liver and isolated hepatocytes. Two groups of calcium antagonists, dihydropyridine-type and nondihydropyridine-type, were examined for their protective effects on A23187-induced liver damage. The former calcium antagonist inhibited cell damage at pharmacological doses, whereas nondihydropyridine-type calcium antagonists were unable to prevent A23187-induced cytotoxicity. Different inhibitors, such as cAMP phosphodiesterase inhibitor OPC3689, calmodulin inhibitor W-7, and C-kinase inhibitor H-7, were tested in isolated hepatocytes to determine whether intracellular signal transduction systems are involved in the liver cell injury produced by A23187. Calcium ionophore A23187-induced LDH activity of the medium was depressed by W-7 and H-7 to 55 +/- 4% and 63 +/- 4% of controls (p less than 0.01), respectively. However, OPC3689 did not show a protective effect. We conclude that A23187-induced liver cell injury was inhibited by dihydropyridine-type calcium antagonists which may interfere with activation of calmodulin and C-kinase.
3rd Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University.
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Matsuda
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000633:toxicity*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004347:Drug Interactions; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000001:Calcimycin; D009568:Nitrendipine; D007770:L-Lactate Dehydrogenase