EJMS

Abstract

Background: Ischemic acute renal failure is a syndrome that develops following a transient drop in total or regional blood flow to the kidney. Reperfusion is essential for the survival of ischemic tissue but causes additional cellular injury. Aldosterone plays an important role as a mediator of renal injury. The aim of the study is to testify the hypothesis of the reno-protective role of a mineralocorticoid antagonist, spironolactone, against renal ischemia/reperfusion (IR) impairment in the rat and to explore the mechanism of preventing its escalation into acute kidney injury. Material and methods: 35 male albino rats were equally divided into control, sham-operated, spironolactone-treated for one or two weeks, IR group and IR groups pre-treated with 20 mg/kg of spironolactone orally for one or two weeks prior to the operation. Two weeks after the operation, animals were sacrificed; the kidneys dissected and prepared to be stained with haematoxylin and eosin stain, toluidine blue and immunohistochemical stain against iNOS and HSP70. Ultrathin sections were also prepared. Morphometric measurements and statistical analysis were done. Results: IR group showed glomerular congestion, widening of the Bowman’s spaces, in addition to significantly increased immunostaining of HSP70 and iNOS. Electron microscopic findings were in the form vacuolated tubular cell cytoplasm, diminished mitochondrial number, dark inclusion bodies and distorted nuclei. Also there were some areas of filtration slits obliteration. Pre-treatment with spironolactone markedly attenuated these deleterious changes and was duration dependent. A significant decline in area percent of the immunostaining of both antibodies and regaining of glomerular and tubular architecture towards uninjured state had been achieved adequately. Conclusion: Pretreatment with spironolactone attenuated subsequent renal IR injury by suppressing inflammatory mediators and heat shock proteins, and this effect was time-dependent.