Enhancement of cyclosporine-induced oxidative damage of kidney mitochondria by iron.
- Author:
Yoon Young JANG
1
;
Eun Sook HAN
;
Chung Soo LEE
;
Young Ki KIM
;
Jin Ho SONG
;
Yong Kyoo SHIN
Author Information
1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Kidney mitochondria;
Cyclosporine;
Iron;
Enhancement of oxidative tissue damage
- MeSH:
Animals;
Chelating Agents;
Cyclosporine;
Deoxyribose;
Edetic Acid;
Hyaluronic Acid;
Iron*;
Kidney*;
Lipid Peroxidation;
Mitochondria*;
Pentetic Acid;
Rats
- From:The Korean Journal of Physiology and Pharmacology
1999;3(6):631-640
- CountryRepublic of Korea
- Language:English
-
Abstract:
The present study investigated the stimulatory effects of iron (or ascorbate) on cyclosporine-induced kidney mitochondrial damage. Damaging effect of 50 muM cyclosporine plus 20 muM Fe2+ on mitochondrial lipids and proteins of rat kidney and hyaluronic acid was greater than the summation of oxidizing action of each compound alone, except sulfhydryl oxidation. Cyclosporine and 100 muM ascorbate showed an enhanced damaging effect on lipids but not on proteins. The peroxidative action of cyclosporine on lipids was enhanced with increasing concentrations of Fe2+. Ferric ion (20 muM) also interacted with cyclosporine to stimulate lipid peroxidation. Damaging action of cyclosporine on mitochondrial lipids was enhanced by ascorbate (100 muM and 1 mM). Iron chelators, DTPA and EDTA, attenuated carbonyl formation induced by cyclosporine plus ascorbate. Cyclosporine (100 muM) and 50 muM Fe2+ (or 100 muM ascorbate) synergistically stimulated degradation of 2- alpha deoxyribose. Cyclosporine (1 to 100 muM) reduced ferric ion in a dose dependent manner, which is much less than ascorbate action. Addition of Fe2+ caused a change in absorbance spectrum of cyclosporine in 230~350 nm of wavelengths. The results show that cyclosporine plus iron (or ascorbate) exerts an enhanced damaging effect on kidney mitochondria. Iron and ascorbate appear to promote the nephrotoxicity induced by cyclosporine.
