Effect of Aliskiren on Renal Cortical Ischemia/Reperfusion Injury in Albino Rats: A Histological and Immunohistochemical Study

Abstract

Background: Ischemia/reperfusion injury (IRI) is a foremost reason for acute kidney injury, which is a common clinical complication having high morbidity rate and lacks effective therapy. Renin-angiotensin system (RAS) activation and angiotensin II level elevation are important risk factors in IRI. Aliskiren (ALS) is the first oral direct rennin inhibitor that blocks the first step in RAS and has been approved for treating hypertension. Aim of work: Investigating whether ALS pretreatment protects the renal cortex of adult male albino rats subjected to IRI. Material and Methods: Thirty adult male albino rats were divided into 3 groups: group I (control group), group II (IRI group): were subjected to IRI procedure, group III (ALS group): rats were pretreated with aliskiren (ALS, 100 mg/kg) twice orally 24h and 1h before IRI and left for 24h of reperfusion before scarification. Blood samples were taken to estimate the levels of blood urea nitrogen (BUN), serum creatinine (SCr) and superoxide dismutase enzyme (SOD). Kidneys sections were stained with HandE and PAS stains and immunohistochemical staining against COX-2 and caspase-3. This was followed by morphometric and statistical analysis. Results: IRI group showed deterioration in renal function tests with massive histological alterations in the Malpighian renal corpuscles and the convoluted tubules. There was significant decrease in optical density of PAS reaction, with significant increase in the mean area% of COX-2 and caspase-3 immunoexpression. ALS group showed significant improvement in renal function tests with preserved normal histology of the renal cortex. There was significant increase in the optical density of PAS reaction, with significant decrease in the mean area% of COX-2 and caspase-3 immunoexpression. Conclusion:A protective effect of ALS was detected in IRI-induced renal cortical damage in adult male albino rats. This was evidenced by laboratory results, histological and immunohistochemical evaluation.

Mas Receptor Blockade Promotes Renal Vascular Response to Ang II after Partial Kidney Ischemia/Reperfusion in a Two-Kidney-One-Clip Hypertensive Rats Model

“…There are three items that influenced the results of this study including RAS, hypertension, and IR. RAS and its components play an important role in the pathogenesis of AKI induced by IR injury [ 17 , 18 , 32 ]. After 45 min of ischemia followed by 4 h of reperfusion, the increase of renal Ang II and the decrease of renal Ang 1–7 were detected [ 12 , 22 ].…”

“…Two-kidney-one-clip (2K1C) as a model of renindependent hypertension and IR alter the balance between two axes of RAS [17][18][19]. AT 2 R and MasR expression decrease in 2K1C [19,20], while IR increased the intrarenal levels of Ang II, AT 2 R, and MasR [12,21,22] and decreased renal cortical Ang II binding [23].…”