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1 Molecular Physiology Unit, Universidad Nacional Autonoma de Mexico, Mexico, City, Mexico; Department of Nephrology, Instituto Nacional de Ciencias Medicas y de la Nutricion, Salvador Zubiran, Mexico, City, Mexico
2 Department of Physiology of Nutrition, Instituto Nacional de Ciencias Medicas y de la Nutricion, Salvador Zubiran, Mexico, City, Mexico
* To whom correspondence should be addressed. E-mail: nab{at}biomedicas.unam.mx.
Obese Zucker rat is a valuable model for studying kidney disease associated with obesity and diabetes. Previous studies have shown that substitution of animal protein with soy ameliorates the progression of renal disease. In order to explore the participation of nitric oxide (NO) and caveolin-1 in this protective effect, we evaluated proteinuria, creatinine clearance, renal structuralal lesions, nitrites and nitrates urinary excretion (UNO2-/NO3V), and mRNA and protein levels of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and caveolin-1 in lean and fatty Zucker rats fed with 20% casein or soy protein diet. After 160 days of feeding with casein, fatty Zucker rats developed renal insufficiency, progressive proteinuria, and renal structural lesions; these alterations were associated with an important fall of UNO2-/NO3V, changes in nNOS and eNOS mRNA levels, together with increased amount of eNOS and caveolin-1 present in plasma membrane proteins of the kidney. In fatty Zucker rats fed with soy, we observed that soy diet improved renal function, UNO2-/NO3V, and proteinuria, and reduced glomeruoesclerosis, tubular dilation, intersticial fibrosis, and extracapilar proliferation. Renal protection was associated with reduction of caveolin-1 and eNOS in renal plasma membrane proteins. In conclusion, our results suggest that renal protective effect of soy protein appears to be mediated by improvement of NO generation and pointed out to caveolin-1 over expression as a potential pathophysiologic mechanism in renal disease.
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