Abstract:

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and antioxidant properties, making it a promising therapy for ischemiareperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadala?l, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n
10), and Tadala?l (10 mg/kg po)-treated I/R group (n
11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240
min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular ?ltration rate was signi?cantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of nacute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadala?l treatment resulted in a signi?cant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadala?l-treated I/R group. These ?ndings demonstrate that Tadala?l possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.