Korean J Intern Med.  1997 Jun;12(2):193-200.

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

• Heo J
• Kim GH
• Lee KS
• Go WU
• Ju HJ
• Park SK
• Song CS
• Song GA
• Cho M
• Yang US
• Moon HK
• Kim YK

Abstract

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 0.5-10 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. 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.

MeSH Terms

Animal
Calcium/metabolism*
Calcium Channel Blockers/pharmacology*
Enzyme Inhibitors/pharmacology*
In Vitro
Lactate Dehydrogenase/secretion
Lipid Peroxidation/drug effects*
Liver/metabolism
Liver/drug effects*
Male
Peroxides/toxicity
Phospholipases A/antagonists & inhibitors*
Rats
Rats, Sprague-Dawley
tert-Butylhydroperoxide