Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1.
Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, 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 Tadalafil (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 filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant 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 Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.
Department of Nephrology and Hypertension, Carmel Medical Center, Haifa, Israel.
Rima
R
Sohotnik
Omri
O
Nativ
Abeer
A
Abbasi
Hoda
H
Awad
Victor
V
Frajewicki
Bishara
B
Bishara
Igor
I
Sukhotnik
Zaher
Z
Armaly
Doron
D
Aronson
Samuel N
SN
Heyman
Ofer
O
Nativ
Zaid
Z
Abassi
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002243:Carbolines / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000652:urine*; D016903:Drug Monitoring / Q000379:methods; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D000068581:Tadalafil
D000209:Acute-Phase Proteins; D015415:Biomarkers; D002243:Carbolines; D015815:Cell Adhesion Molecules; D000071068:Lipocalin-2; D054834:Lipocalins; D058986:Phosphodiesterase 5 Inhibitors; D011518:Proto-Oncogene Proteins; D000068581:Tadalafil; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat