INTRODUCTION & OBJECTIVES: Renal ischemia reperfusion injury can be seen in several conditions such as nephron sparing surgery where renal pedicle clamping is often required, sepsis and heart transplantation. Free radicals can lead to acute renal damage and long-term chronic kidney disease. Many strategies have been tested to protect against such ischemic injury but with limited success. The aim of the current study was to test the nephroprotective effects of Tadalafil, a PDE5 inhibitor, in experimental renal ischemia-reperfusion (I/R) injury model.
MATERIAL & METHODS: The study was carried out at the depatment of physiology, Technion Institute of technology, Haifa, Israel. Sprague-Dawley rats were divided into 3 groups: Normal controls, vehicle-treated I/R, and Tadalafil (10 mg/kg, PO) treated I/R groups. After removal of right kidney and collection of 2 baseline urine samples, the left renal artery was occluded for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups as well as urine level of two acute kidney injury markers (NGAL and KIM-1) were determined.
RESULTS: In the Tadalafil treated I/R group, glomerular filtration rate (GFR), urinary Na excretion and systemic blood pressure reduced significantly compared to that in control group. The ischemic kidneys of the control group showed remarkable cast formation, necrosis and congestion, a consistent pattern of acute tubular necrosis. In addition, urinary excretion of NGAL and KIM-1, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant amelioration of the adverse histological alterations of the ischemic kidneys. The urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil treated I/R group.
CONCLUSIONS: These findings demonstrate that Tadalafil possesses nephroprotective effects in rat kidney subjected to I/R insult. This approach may compose a prophylactic therapy for patients with ischemic AKI.