Elsevier

Kidney International

Volume 67, Issue 5, May 2005, Pages 1890-1898
Kidney International

Vascular Biology – Hemodynamics – Hypertension
Effects of NADPH oxidase inhibitor in diabetic nephropathy

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Effects of NADPH oxidase inhibitor in diabetic nephropathy.

Background

We used apocynin to test the hypothesis that superoxide anion (O2) from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase underlies the development of diabetic nephropathy in the rat.

Methods

Rats received apocynin (16 mg/kg/day) from 2 to 8 weeks after inducing diabetes mellitus (DM) with streptozotocin.

Results

DM increased excretion of hydrogen peroxide (H2O2), lipid peroxidation products (LPO), nitric oxide products (NOx), and protein. The kidneys of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), and increased mesangial matrix with expression of fibronectin and collagen I. Apocynin prevented the increase in excretion of H2O2, LPO, and protein in diabetic rats, increased renal NOx generation, and prevented the increased renal expression of gp91phox and the membrane fraction of p47phox, and reverted the mesangial matrix expansion.

Conclusion

Activation of NADPH oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited NO generation, despite enhanced eNOS expression in a model of diabetic nephropathy. Apocynin prevents these changes and the associated proteinuria.

KEYWORDS

NADPH oxidase
nitric oxide synthase
proteinuria
diabetic nephropathy
apocynin

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