الفهرس | Only 14 pages are availabe for public view |
Abstract The reno-protective effect of systemic Sildenafil administration in renal ischemia reperfusion injury (IR) animal models has been proved. Nevertheless, the local effect of Sildenafil on IR has not been established yet. Therefore, we designed a new canine model of IR injury to investigate the effect of local Sildenafil administration during renal ischemia. One hundred and twenty male mongrel dogs were classified into 5 groups (each consists of 24 dogs): sham (right nephrectomy without left renal ischemia), oral control (OC) group ( right nephrectomy and left renal ischemia for 60 min.), oral Sildenafil (OS) group (as control with oral Sildenafil 1mg/kg 60 min before ischemia), local (LC) group (local perfusion of ischemic left kidney with saline and heparin for 5min) and local Sildenafil(LS) group (local perfusion with sildenafil 0.5 mg/kg). Each group is subdivided into 4 subgroups (6dogs each) according to time of scarification (1, 3, 7 and 14 days). Renal function and histopathological changes were compared between different groups. The expression of cleaved caspase-3 was assessed by immunohistochemical staining. Renal function improved significantly in Sildenafil-treated groups in comparison to their control groups (p<0.05). Sildenafil treated group showed significant attenuation of cortical and medullary damage scores than other groups. On comparison of LS and OS groups, LS group is associated with statistically significant better improvement of renal function and lower cortical and medullary damage score. Sildenafil decreased expression of Caspase-3 in renal tissue which is more prominent in LS group. Local administration of Sildenafil provides much more renoprotective effect against IR than do systemic administration. These results may provide a base for its application in the process of renal transplantation in human during renal perfusion. |