title: Effect of Ca2+ channel blockers, external Ca2+ and phospholipase A2 inhibitors on t-butylhydroperoxide-induced lipid peroxidation and toxicity in rat liver slices.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine and Physiology, College of Medicine, Pusan National University, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Heo
authors.forename: G H
authors.initials: GH
authors.lastname: Kim
authors.forename: K S
authors.initials: KS
authors.lastname: Lee
authors.forename: W U
authors.initials: WU
authors.lastname: Go
authors.forename: H J
authors.initials: HJ
authors.lastname: Ju
authors.forename: S K
authors.initials: SK
authors.lastname: Park
authors.forename: C S
authors.initials: CS
authors.lastname: Song
authors.forename: G A
authors.initials: GA
authors.lastname: Song
authors.forename: M
authors.initials: M
authors.lastname: Cho
authors.forename: U S
authors.initials: US
authors.lastname: Yang
authors.forename: H K
authors.initials: HK
authors.lastname: Moon
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010545:Peroxides / Q000633:toxicity; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D020122:tert-Butylhydroperoxide
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D010545:Peroxides; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium