Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney mitochondria and microsomes

Suk Ha Lee, Young Chul Yoon, Yoon Young Jang, Jin Ho Song, Eun Sook Han, Chung Soo Lee

Research output: Contribution to journalArticle

Abstract

The stimulatory effect of iron and ascorbate on the damaging action of cyclosporine in kidney mitochondria, microsomes and epithelial cells was examined. Cyclosporine induced malondialdehyde formation and hydrogen peroxide production in mitochondria and attenuated the activity of MnSOD and glutathione peroxidase. The damaging effect of cyclosporine (50 μM) plus Fe2+ (20 μM) on mitochondrial and microsomal lipids and proteins as well as mitochondrial thiols was greater than the summation of the oxidizing action of cyclosporine alone and Fe2+ alone. As for tissue components, iron enhanced cyclosporine-induced viability loss in kidney epithelial cells. Fe2+, EDTA and H2O2-induced 2-α deoxyribose degradation was attenuated by 10 mM DMSO and 200 μM DTPA but not affected by 200 μM cyclosporine. The addition of Fe2+ caused a change in the absorbance spectrum of cyclosporine in the wavelength range 230-350 nm. The simultaneous addition of cyclosporine (50 μM) and ascorbate (100 μM) showed the enhanced peroxidative effect on mitochondrial and microsomal lipids, which was inhibited by DTPA and EDTA (1 mM). Similar to iron, ascorbate enhanced cyclosporine-induced cell viability loss. The results show that iron and ascorbate promote the damaging action of cyclosporine in kidney cortex mitochondria and microsomes and in kidney epithelial cells, which may contribute to the enhancement of cyclosporine-induced nephrotoxicity.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalPharmacological Research
Volume43
Issue number2
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Ascorbate
  • Cyclosporine
  • Iron
  • Kidney damage
  • Promoting effect

ASJC Scopus subject areas

  • Pharmacology

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