Ciclopirox protects mitochondria from hydrogen peroxide toxicity

Sun J. Lee, Youngman Jin, Hye Young Yoon, Byung Ok Choi, Hyoung Chun Kim, Yu Kyoung Oh, Hee Sun Kim, Woo Ki Kim

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The mitochondrial respiratory chain produces reactive oxygen species (ROS) during normal electron transport. Despite producing ROS, mitochondria are vulnerable to oxidative stress. Mitochondrial dysfunction has been associated with many degenerative diseases, making it important to identify compounds that protect mitochondria from ROS-mediated toxicity. Here we report that ciclopirox (CPX) blocks H 2O 2-induced mitochondrial injury by maintaining mitochondrial transmembrane potential (Δψm). CPX completely blocked H 2O 2-stimulated release of lactate dehydrogenase (a marker of cell death) and decrease in MTT reduction (a marker of mitochondrial function) in adenocarcinoma SK-HEP-1 cells. H 2O 2 rapidly depolarized the Δψm, and CPX blocked this H 2O 2-stimulated Δψm decrease. Similar data were obtained in experiments using mitochondria isolated from rat liver. Furthermore, CPX effectively inhibited H 2O 2-induced mitochondrial permeability transition pore (MPTP) opening. In de-energized mitochondria, however, CPX did not inhibit Ca 2+-evoked MPTP opening, indicating that CPX is not a direct inhibitor of the MPTP. Oxygen consumption studies showed that in the presence of pyruvate and malate CPX restored the rate of state 3 to state 4 respiration decreased by H 2O 2. Consistent with this, CPX replenished ATP levels lowered by H 2O 2. The present results indicate that CPX protects SK-HEP-1 cells from H 2O 2 cytotoxicity by inhibiting Δψm decrease and indirectly preventing MPTP opening.

Original languageEnglish
Pages (from-to)469-476
Number of pages8
JournalBritish Journal of Pharmacology
Volume145
Issue number4
DOIs
Publication statusPublished - 2005 Jun 1

Keywords

  • Cell death
  • Ciclopirox
  • Hydrogen peroxide
  • Mitochondrial permeability transition pore
  • Mitochondrial transmembrane potential

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Lee, S. J., Jin, Y., Yoon, H. Y., Choi, B. O., Kim, H. C., Oh, Y. K., Kim, H. S., & Kim, W. K. (2005). Ciclopirox protects mitochondria from hydrogen peroxide toxicity. British Journal of Pharmacology, 145(4), 469-476. https://doi.org/10.1038/sj.bjp.0706206