KMID : 0338419970120020193
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The Korean Journal of Internal Medicine 1997 Volume.12 No. 2 p.193 ~ p.200
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Effect of Ca2+ Channel Blockers, External Ca2+ and Phospholipase A2 Inhibitors on t-butylhydroperoxide-induced Lipid Peroxidation and Toxicity in Rat Liver Slices
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Jeong Heo/Jeong Heo
Gwang Ha Kim/Kyoung Seog Lee/Won Uk Go/Hyung Jun Ju/Seung Keun Park/Chul Soo Song/Geun Am Song/Mong Cho/Ung Suk Yang/Han Kyu Moon/Yong Keun Kim
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Abstract
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Objectives: This study was undertaken to examine the effect of oxidant on lipid peroxidation and lethal cell injury in rat liver slices.
Methods: 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.
Results: t-BHP increased lipid peroxidation and LDH release in a dose-dependent manner over concentrations of 0.5?10mM. 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.
Conclusions: 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.
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KEYWORD
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