Effects of NADPH oxidase inhibitor in diabetic nephropathy.
BACKGROUND
We used apocynin to test the hypothesis that superoxide anion (O(-) (2)) 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 (H(2)O(2)), 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 H(2)O(2), 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.


CONCLUSIONS
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.
Asaba
Kensuke
K
Division of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan.
Tojo
Akihiro
A
Onozato
Maristela Lika
ML
Goto
Atsuo
A
Quinn
Mark T
MT
Fujita
Toshiro
T
Wilcox
Christopher S
CS
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D000098:Acetophenones; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D009573:Nitrites; D010750:Phosphoproteins; D013481:Superoxides; C056165:acetovanillone; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1