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Published on: October 12, 2015
Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats
Shigeru Owada1, Sumie Goto, Kenji Bannai
1Dialysis Unit, Asao Clinic, Kawasaki, Japan.
Background/Aim:
Indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic renal failure (CRF). This study aimed at determining whether IS impairs antioxidative systems (redox status) in the kidney.
Methods:
IS was orally administered to normal and subtotally nephrectomized (three fourths and five sixths) rats (CRF rats) for 2 weeks. By use of in vivo and ex vivo electron spin resonance spectroscopy, the kidney redox status was evaluated using carbamoyl-PROXYL as a radical spin probe in living rats, and the kidney superoxide scavenging activity was measured. Immunohistochemistry of superoxide dismutase (SOD) in the kidney was performed.
Results:
Administration of IS increased serum and kidney levels of IS and serum creatinine and decreased creatinine clearance. CRF rats showed reduced spin reduction rate, prolonged half-life of the spin probe, and reduced superoxide scavenging activity and SOD-positive areas in the kidney as compared with normal rats. Administration of IS further reduced radical spin reduction rate, prolonged half-life of the spin probe, and reduced superoxide scavenging activity and SOD-positive areas in the kidneys.
Conclusions:
Administration of IS reduced superoxide scavenging activity in the kidneys of normal and CRF rats. Thus, the nephrotoxicity of IS may be induced by impairing the antioxidative systems in the kidney.
Insights
Indoxyl sulfate (IS), a uremic toxin, impairs kidney antioxidative systems. This study shows IS reduces superoxide scavenging activity, contributing to kidney damage in chronic renal failure.
Area of Science:
- Nephrology
- Toxicology
- Biochemistry
Background:
- Indoxyl sulfate (IS) is a uremic toxin implicated in chronic renal failure (CRF) progression.
- The impact of IS on renal antioxidative systems remains incompletely understood.
Purpose of the Study:
- To investigate the effect of indoxyl sulfate (IS) on kidney redox status.
- To determine if IS impairs antioxidative defense mechanisms in the kidney.
Main Methods:
- Oral administration of IS to normal and subtotally nephrectomized (CRF) rats.
- In vivo and ex vivo electron spin resonance (ESR) spectroscopy using carbamoyl-PROXYL to assess kidney redox status.
- Measurement of kidney superoxide scavenging activity and immunohistochemical analysis of superoxide dismutase (SOD).
Main Results:
- IS administration increased serum and kidney IS levels, elevated serum creatinine, and reduced creatinine clearance.
- CRF rats exhibited impaired redox status, reduced superoxide scavenging activity, and decreased SOD expression.
- IS administration further exacerbated these impairments in both normal and CRF rats.
Conclusions:
- Indoxyl sulfate (IS) administration significantly reduces superoxide scavenging activity in the kidneys.
- IS-induced nephrotoxicity may stem from the impairment of renal antioxidative systems.
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