Effect of Ca2+ channel blockers, external Ca2+ and phospholipase A2 inhibitors on t-butylhydroperoxide-induced lipid peroxidation and toxicity in rat liver slices

• Published in: The Korean journal of internal medicine Vol. 12; no. 2; pp. 193 - 200
• Main Authors: Heo, J, Kim, G H, Lee, K S, Go, W U, Ju, H J, Park, S K, Song, C S, Song, G A, Cho, M, Yang, U S, Moon, H K, Kim, Y K
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Association of Internal Medicine 01.06.1997
• Subjects: Animals; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Enzyme Inhibitors - pharmacology; In Vitro Techniques; L-Lactate Dehydrogenase - metabolism; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - metabolism; Male; Original; Peroxides - toxicity; Phospholipases A - antagonists & inhibitors; Phospholipases A2; Rats; Rats, Sprague-Dawley; tert-Butylhydroperoxide
• ISSN: 1226-3303; 2005-6648
• DOI: 10.3904/kjim.1997.12.2.193

This study was undertaken to examine the effect of oxidant on lipid peroxidation and lethal cell injury in rat liver slices. t-Butylhydroperoxide (t-BHP) was employed as a model of an oxidant. The lipid peroxidation and lethal cell injury were estimated by measuring the formation of malondialdehyde (MDA) and lactate dehydrogenase (LDH) release, respectively. t-BHP increased lipid peroxidation and LDH release in a dose-dependent manner over concentrations of 0.5-10 mM. t-BHP-induced lipid peroxidation was completely prevented by an antioxidant, N,N-diphenyl-p-phenylenediamine (DPPD), but LDH release was partially decreased. Both t-BHP-induced lipid peroxidation and LDH release were significantly protected by iron chelator, deferoxamine, sulfhydryl reducing agent, dithiothreitol and glutathione. Ca2+ channel blockers, verapamil, diltiazem and nifedipine exerted a significant protective effect against t-BHP-induced lipid peroxidation and LDH release. By contrast, addition of external Ca2+ chelator, ethylene glycol bis(b-aminoethyl ether)-N,N-tetraacetic acid (EGTA) did not alter t-BHP-induced lipid peroxidation, whereas t-BHP-induced lethal cell injury was significantly prevented. Phospholipase A2 (PLA2) inhibitors, mepacrine and butacaine produced a partial protective effect. These results suggest that t-BHP induces cell injury by lipid peroxidation-dependent and -independent mechanisms which can be partially prevented by Ca2+ channel blockers and PLA2 inhibitors.