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KMID : 0811719990030060631
Korean Journal of Physiology & Pharmacology
1999 Volume.3 No. 6 p.631 ~ p.640
Enhancement of Cyclosporine-Induced Oxidative Damage of Kidney Mitochondria by Iron
Yoon Young Jang
Eun Sook Han/Chung Soo Lee/Young Ki Kim/Jin Ho Song/Yong Kyoo Shin
Abstract
The present study investigated the stimulatory effects of iron (or ascorbate) on cyclosporine-induced kidney mitochondrial damage. Damaging effect of 50¥ìM cyclosporine plus 20¥ìMFe2+ 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¥ìM 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¥ìM) also interacted with cyclosporine to stimulate lipid peroxidation. Damaging action of cyclosporine on mitochondrial lipids was enhanced by ascorbate (100¥ìMand1mM). Iron chelators, DTPA and EDTA, attenuated carbonyl formation induced by cyclosporine plus ascorbate. Cyclosporine (100¥ìM) and 50¥ìMFe2+ (or100¥ìMascorbate) synergistically stimulated degradation of 2?¥á deoxyribose. Cyclosporine (1to100¥ìM) 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.
KEYWORD
Kidney mitochondria, Cyclosporine, Iron, Enhancement of oxidative tissue damage,
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