The role of lipid peroxidation in menadione-mediated toxicity in cardiomyocytes

Woan Fang Tzeng, Jia Luen Lee, Tzeon Jye Chiou

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

The role of lipid peroxidation in menadione-mediated toxicity was studied in neonatal rat Cardiomyocytes. Incubation of Cardiomyocytes with menadione resulted in depleted cellular glutathione levels, increased intracellular Ca2+ and increased lipid peroxidation which all occurred prior to cell degeneration. Pre-treatment of cells with cysteine suppressed the menadione-induced cell degeneration and prevented changes in glutathione levels, intracellular Ca2+. and lipid peroxidation. Pre-treatment of cells with fura-2 acetoxymethyl ester, a Ca2+ chelator, reduced menadione-induced c cel degeneration and lipid peroxidation but it did not block cellular glutathione depletion. Pre-treatment of cells with deferoxamine mesylate. an iron chelator, also reduced both menadione-induced cell degeneration and lipid peroxidation: however, it did not prevent the menadione-induced increase in intracellular Ca2+, nor the depletion of glutathione. Thus, the inhibition of menadione-induced lipid peroxidation by deferoxamine mesylate prevented cell degeneration even though intracellular Ca2+ remained elevated and glutathione remained depleted. The protective effects of deferoxamine mesylate and fura-2 AM on menadione's toxicity were inhibited by addition of FeCl3 to cells. Ferric ions did not inhibit the protective effect of cysteine. These data suggest that menadione-induced cardiomyocyte degeneration is directly linked to iron-dependent lipid peroxidation and less tightly coupled to elevation in intracellular Ca2+ or depletion of glutathione.

Original languageEnglish
Pages (from-to)1999-2008
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number9
DOIs
Publication statusPublished - Sep 1995
Externally publishedYes

Keywords

  • Ca
  • Cardiomyocyte
  • Glutathione
  • Lipid peroxidation
  • Menadione

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'The role of lipid peroxidation in menadione-mediated toxicity in cardiomyocytes'. Together they form a unique fingerprint.

Cite this