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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.

Heo J, Kim GH, Lee KS, Go WU, Ju HJ, Park SK, Song CS, Song GA, Cho M, Yang US, Moon HK, Kim YK - Korean J. Intern. Med. (1997)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Physiology, College of Medicine, Pusan National University, Korea.

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.

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Related in: MedlinePlus

Effect of DPPD on t-BHP-induced lipid peroxidation (A) and LDH release (B). Liver slices were treated with 1 mM t-BHP for 60 min at 37°C in the presence or absence of 20 mM DPPD. Data are mean ± SE of four experiments. *p<0.05, **p<0.01 compared with t-BHP alone.
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f3-kjim-12-2-193-11: Effect of DPPD on t-BHP-induced lipid peroxidation (A) and LDH release (B). Liver slices were treated with 1 mM t-BHP for 60 min at 37°C in the presence or absence of 20 mM DPPD. Data are mean ± SE of four experiments. *p<0.05, **p<0.01 compared with t-BHP alone.

Mentions: In order to determine whether antioxidant could prevent lipid peroxidation as well as t-BHP-induced cell injury as estimated by LDH release, the effect of a phenolic antioxidant, DPPD, was examined. As shown in Fig. 3, 20mM DPPD exerted a siginficant protective effect against lipid peroxidation and LDH release caused by 1mM t-BHP. However, the extent of protective effect on LDH release was less than that on lipid peroxidation. t-BHP-induced lipid peroxidation was completely prevented by DPPD, whereas t-BHP-induced LDH release was partially (although significantly) reduced.


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 - Korean J. Intern. Med. (1997)

Effect of DPPD on t-BHP-induced lipid peroxidation (A) and LDH release (B). Liver slices were treated with 1 mM t-BHP for 60 min at 37°C in the presence or absence of 20 mM DPPD. Data are mean ± SE of four experiments. *p<0.05, **p<0.01 compared with t-BHP alone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4531990&req=5

f3-kjim-12-2-193-11: Effect of DPPD on t-BHP-induced lipid peroxidation (A) and LDH release (B). Liver slices were treated with 1 mM t-BHP for 60 min at 37°C in the presence or absence of 20 mM DPPD. Data are mean ± SE of four experiments. *p<0.05, **p<0.01 compared with t-BHP alone.
Mentions: In order to determine whether antioxidant could prevent lipid peroxidation as well as t-BHP-induced cell injury as estimated by LDH release, the effect of a phenolic antioxidant, DPPD, was examined. As shown in Fig. 3, 20mM DPPD exerted a siginficant protective effect against lipid peroxidation and LDH release caused by 1mM t-BHP. However, the extent of protective effect on LDH release was less than that on lipid peroxidation. t-BHP-induced lipid peroxidation was completely prevented by DPPD, whereas t-BHP-induced LDH release was partially (although significantly) reduced.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Physiology, College of Medicine, Pusan National University, Korea.

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.

Show MeSH
Related in: MedlinePlus