Indoxyl sulfate induces complex redox alterations in mesangial cells
Andrew K Gelasco1, John R Raymond
1Nephrology Division, Medical Univ. of South Carolina, 96 Jonathan Lucas St., 829 CSB, Charleston, SC 29425-2227, USA. gelascoa@musc.edu
American Journal of Physiology. Renal Physiology
|January 26, 2006
Summary
Indoxyl sulfate, a uremic toxin, alters kidney cell redox balance and increases reactive oxygen species (ROS) production at concentrations found in chronic kidney disease patients. This suggests a mechanism for its role in disease progression.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Indoxyl sulfate is a protein metabolite and uremic toxin found in chronic renal insufficiency.
- Mesangial cell redox status is linked to glomerular damage via mitogen-activated protein kinase activation and cell proliferation.
Purpose of the Study:
- To investigate the effects of indoxyl sulfate on mesangial cell redox status.
- To elucidate the mechanism of indoxyl sulfate toxicity in renal cells.
Main Methods:
- Redox microphysiometry to measure mesangial cell reduction rate.
- CM-DCF fluorescent dye to detect intracellular reactive oxygen species (ROS).
- Electron paramagnetic spin resonance spectroscopy with spin traps to analyze radical production.
Main Results:
- Indoxyl sulfate increased mesangial cell reduction rate concentration-dependently.
- Indoxyl sulfate induced intracellular ROS production (EC50 = 550 microM).
- Indoxyl sulfate increased extracellular O2-* and intracellular hydroxyl radical production.
Conclusions:
- Indoxyl sulfate alters mesangial cell redox status at pathological concentrations.
- Indoxyl sulfate induces ROS production and radical formation, contributing to its toxicity.
- These redox changes may mediate glomerular damage in chronic kidney disease.
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