Effect of spironolactone on diabetic nephropathy in albino rats: ultrastructural and immunohistochemical study

Abstract

<p class="abstract"><strong>Background:</strong> Diabetic nephropathy (DN) has become one of the most common causes of end stage renal disease (ESRD). Hyperglycemia induces oxidative stress in renal tubular epithelial cells that initiate tubulointerstitial fibrosis, which is a characteristic feature of diabetic nephropathy that becomes progressively complicated by renal failure. Aim: To assess the effect of spironolactone (SPL) on WT-1 protein expression and ultrastructural changes associated with the progression of experimental diabetic nephropathy (DN).</p><p class="abstract"><strong>Methods:</strong> Forty female albino rats were divided into five groups. Group I (control group), Group II (untreated diabetic rats), Group III (insulin-treated diabetic rats), Group IV (spironolactone-treated diabetic rats) and Group V (insulin and spironolactone-treated diabetic rats). At the 4<sup>th</sup> and 8<sup>th</sup> weeks, 4 rats from each group were sacrificed and renal tissue and blood samples were obtained. The rats were anaesthetized using ether inhalation. Each kidney was longitudinally divided and processed for immunohistochemical analysis with rabbit polyclonal anti-WT-1 Antibody and electron microscopic examination.</p><p class="abstract"><strong>Results:</strong> Treatment of STZ-induced diabetic rats with insulin and spironolactone (Group V) showed improvement in renal corpuscles as well as their capsular space, the basement membrane became normal with preserved minor and major processes and subpodocytic space, most of the proximal convoluted tubules retained their brush border, and their cells showed normal euchromatic nuclei and scattered mitochondria with apical microvilli, which is similar to the findings of the control group. Quantitative analyses showed significant increase in area of fibrosis and focal thickening of the glomerular basement membrane in non-SPL treated groups. There was a marked decrease in proteinuria compared to other treated groups. The results were better after 8 weeks compared to those after 4 weeks.</p><strong>Conclusions:</strong> The administration of SPL significantly prevented the extent of interstitial fibrosis in the diabetic kidney.