Effect of Ca2+ channel blockers, external Ca2+ and phospholipase A2 inhibitors on t-butylhydroperoxide-induced lipid peroxidation and toxicity in rat liver slices
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...
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Published in | The Korean journal of internal medicine Vol. 12; no. 2; pp. 193 - 200 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Korea (South)
Korean Association of Internal Medicine
01.06.1997
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Abstract | 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. |
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AbstractList | 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. |
Author | Go, W U Song, G A Moon, H K Song, C S Kim, Y K Yang, U S Heo, J Ju, H J Lee, K S Park, S K Kim, G H Cho, M |
AuthorAffiliation | Department of Physiology, College of Medicine, Pusan National University, Pusan, Korea Department of Internal Medicine, College of Medicine, Pusan National University, Pusan, Korea |
AuthorAffiliation_xml | – name: Department of Physiology, College of Medicine, Pusan National University, Pusan, Korea – name: Department of Internal Medicine, College of Medicine, Pusan National University, Pusan, Korea |
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Cites_doi | 10.1016/0168-8278(91)90947-A 10.1016/0006-2952(86)90369-2 10.1016/0014-5793(84)80202-1 10.1152/ajpheart.1986.251.1.H71 10.1016/0003-9861(89)90122-7 10.1038/ki.1988.147 10.1016/0006-2952(92)90074-S 10.1016/0006-2952(84)90136-9 10.1016/0002-9149(85)90607-1 10.1016/0006-2952(93)90634-9 10.1016/0003-2697(78)90342-1 10.1016/0041-008X(85)90255-8 10.1073/pnas.79.22.6842 10.1038/ki.1994.263 10.1006/abio.1976.9999 |
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Snippet | 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... |
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SubjectTerms | 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 |
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Title | 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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