da-8159 and Reperfusion-Injury

The aim of this study was to investigate and compare the effects of udenafil and mannitol in an experimental renal ischemia-reperfusion (I/R) injury model.. A total of 64 female Wister Albino rats were used. Right nephrectomy was performed in all groups. In the control group; I/R injury was not performed. In the I/R group; left renal pedicle was clamped for 45 minutes and then underwent 60 minutes and 24 hours of reperfusion. In the mannitol group; 1 mL 20% mannitol was given intravenously 15 minutes before clamping. In the udenafil group; 10-mg/kg udenafil was given orally 1 hour before clamping. Creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, malondialdehyde, neutrophil gelatinase associated lipocalin (NGAL), histological examination and DNA damage (Comet Assay method) levels were compared in tissue, serum and urine samples.. Udenafil had a better protective effect than mannitol according to biochemical parameters (Cr, BUN, Cr clearance, and NGAL levels) and histopathological findings when compared with the I/R group. In the Comet sampling analysis no significant difference was detected.. Udenafil has a better renoprotective effect than mannitol against I/R injury and this effect supports more functional improvements. Further clinical trials are needed to demonstrate those effects and clinical utility of udenafil for that purpose in humans.

Topics: Acute-Phase Proteins; Animals; Constriction; Diuretics, Osmotic; Female; Kidney; Lipocalin-2; Lipocalins; Malondialdehyde; Mannitol; Nephrectomy; Phosphodiesterase 5 Inhibitors; Protective Agents; Proto-Oncogene Proteins; Pyrimidines; Rats, Wistar; Reperfusion Injury; Sulfonamides

The aim of this study was to investigate the antioxidant properties of udenafil citrate (1.4 mg kg(-1) -2.8 mg kg(-1) ), dexmedetomidine 25 μg kg(-1) and piracetam 200 mg kg(-1) administered on ipsilateral/contralateral testes after ischaemia in a rat model of testicular torsion/detorsion (T/D) and define its protective effect histologically. Fifty-six Wistar albino rats were included and randomly assigned into 6 groups. No intervention was performed in control group (Group 1, n = 8) and in torsion/detorsion group, (Group 2, n = 8). Udenafil 1.4 mg kg(-1) was given to torsion/detorsion group (Group 3, n = 10), udenafil 2.8 mg kg(-1) was given to torsion/detorsion group (Group 4, n = 10), piracetam 200 mg kg(-1) was given to torsion/detorsion group (Group 5, n = 10) and dexmedetomidine 25 μg kg(-1) was given to torsion/detorsion group (Group 6, n = 10) intraperitoneally after 60 mins of testicular torsion. Biochemical and histopathological testicular injury were evaluated. When the tissue was examined by TOS values, Group 3, Group 4 and Group 5 were significantly lower than Group 2. In contrary Group 6 values were significantly higher than Group 2. The increasing doses of udenafil demonstrated antioxidant properties on the testis tissue and histopathological that protects the testicles.

Topics: Animals; Dexmedetomidine; Disease Models, Animal; Male; Piracetam; Protective Agents; Pyrimidines; Rats; Rats, Wistar; Reperfusion Injury; Spermatic Cord Torsion; Sulfonamides; Treatment Outcome

Ischemia-reperfusion injury can cause testicular damage and phosphodiesterase inhibitors are reported to regulate antioxidant activity. We investigated the prevention of ipsilateral and contralateral testicular damage using 2 phosphodiesterase inhibitors after testicular detorsion in rats.. A total of 28 adult male rats were randomly divided into 4 groups of 7 each, including group 1-sham operation, group 2-testicular torsion and detorsion, group 3- testicular torsion and detorsion with sildenafil administration before detorsion and group 4- testicular torsion and detorsion with udenafil administration before detorsion. Tissue levels of malondialdehyde, total sulfhydryl and nitrite were evaluated, and histopathological changes in the groups were examined.. Compared to group 1 significantly increased tissue malondialdehyde (p = 0.001), significantly decreased total sulfhydryl (p = 0.038) and insignificantly increased nitrite were found in group 2. Compared to group 2 malondialdehyde decreased significantly and total sulfhydryl increased significantly in groups 3 and 4. The decrease in nitrite was insignificant in the latter 2 groups. Histopathology revealed increased hemorrhage, congestion and edema in group 2 rats. The testicular injury score was lower in groups 3 and 4. In group 2 grades II to IV injury was detected while most specimens in treated groups showed grade II injury.. This study indicates that intraperitoneal administration of sildenafil and udenafil efficiently suppresses radical production while decreasing histological changes after testicular ischemia-reperfusion injury.

Topics: Animals; Disease Models, Animal; Drug Therapy, Combination; Injections, Intraperitoneal; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sildenafil Citrate; Sulfonamides; Sulfones; Testicular Diseases; Testis

DA-8159 is a pyrazolopyrimidinone derivative which exhibits potent and selective phosphodiesterase type 5 (PDE5) inhibition. The aim of this study was to investigate the effects of DA-8159 on inducing a penile erection in rabbits with an acute spinal cord injury (ASCI). DA-8159 was given either orally (1, 3, or 10 mg/kg) or intravenously (0.1 or 0.3 mg/kg) to conscious male albino rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion SCI rabbits. Erection was evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. DA-8159 induced a dose-dependent erection in both transection and ischemic-reperfusion ASCI rabbits. The efficacy of DA-8159 was potentiated by an intravenous injection of sodium nitroprusside, a nitric oxide donor. Potentiation of the effect by nitric oxide donor implies that DA-8159 can enhance the erectile activity during sexual arousal. These results suggest that DA-8159 may be useful for treating erectile dysfunction in patients with an SCI.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Acute Disease; Animals; Area Under Curve; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Erectile Dysfunction; Male; Penile Erection; Pyrimidines; Rabbits; Reperfusion Injury; Spinal Cord; Spinal Cord Injuries; Sulfonamides