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Effects of NADPH oxidase inhibitor in diabetic nephropathy

Kensuke Asaba1, Akihiro Tojo, Maristela Lika Onozato

  • 1Division of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan.

Kidney International
|April 21, 2005
PubMed
Abstract

Insights

Apocynin treatment prevented kidney damage in diabetic rats by inhibiting NADPH oxidase activation, reducing oxidative stress, and improving nitric oxide generation, thus preventing proteinuria.

Area of Science:

  • Nephrology
  • Oxidative Stress Research
  • Pharmacology

Background:

  • Diabetic nephropathy is a significant complication of diabetes mellitus.
  • Oxidative stress, particularly from NADPH oxidase, is implicated in its development.
  • Superoxide anion (O(-) (2)) production by NADPH oxidase is a key factor.

Purpose of the Study:

  • To test the hypothesis that NADPH oxidase activity underlies diabetic nephropathy.
  • To investigate the protective effects of apocynin, an NADPH oxidase inhibitor.

Main Methods:

  • Diabetes mellitus (DM) was induced in rats using streptozotocin.
  • Apocynin (16 mg/kg/day) was administered from 2 to 8 weeks post-induction.
  • Kidney function and molecular markers of oxidative stress and fibrosis were assessed.

Main Results:

  • Diabetic rats showed increased markers of oxidative stress (H(2)O(2), LPO) and kidney damage (proteinuria, mesangial expansion).
  • Increased expression of NADPH oxidase components (p47phox, gp91phox) and fibrotic markers (fibronectin, collagen I) was observed.
  • Apocynin treatment attenuated oxidative stress markers, prevented p47phox translocation, and reverted mesangial matrix expansion.

Conclusions:

  • NADPH oxidase activation and subsequent oxidative stress contribute to diabetic nephropathy.
  • Apocynin effectively inhibits these pathological changes, including proteinuria.
  • Targeting NADPH oxidase offers a potential therapeutic strategy for diabetic nephropathy.

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