Effect of PDE 5 Inhibitor-Avanafil on Renal Ischemia/Reperfusion Injury in Rats

Abstract

Aim:Renal ischemia-reperfusion injury (RI/RI) damages many organs, especially the kidney. Phosphodiesterase (PDE) 5 inhibitors has antioxidant and anti-inflammatory effects. Avanafil (AVA) is a second-generation PDE 5 inhibitor with greater PDE isoform selectivity. The aim of this study is to investigate the effects of AVA on RI/RI in rats.Materials and Methods:Forty rats were randomly divided into five groups (n=8): Sham; AVA 10; RI/RI; RI/RI + 5 mg/kg AVA, and RI/RI + 10 mg/ kg AVA. RI/RI in rats was established by clamping renal artery. An acute surgical experiment was performed for the induction of renal ischemia for 45 min by renal artery clamping followed by reperfusion for 24 h. Kidney tissues were investigated biochemically [malondialdehyde (MDA) and glutathione (GSH) with ELISA], molecularly [relative quantification of IL-1β, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α) mRNA gene expression with qRT-PCR], and histopathologically (staining with Harris hematoxylin and eosin Y).Results:AVA administration ameliorated disturbances in MDA and GSH levels caused by RI/RI. AVA treatment improved the increase in the mRNA expressions of IL-1β, NF-κB, and TNF-α in kidney tissues induced ischemia/reperfusion injury. AVA administration ameliorated histopathologic injury in kidney tissues caused by renal ischemia reperfusion. Moreover, the values closest to those of the sham group were obtained by administering 10 mg/kg AVA to rats with RI/RI.Conclusion:AVA administration improved renal ischemia/reperfusion-induced tissue injury by alleviating oxidative stress and inflammatory cascades that could be important in ischemia-reperfusion injury. These findings may provide a mechanistic basis for using AVA to treat RI/RI.

Keywords

• anti-inflammatory
• antioxidant
• avanafil
• phosphodiesterase 5 inhibitor
• renal ischemia/reperfusion injury