الفهرس 
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Abstract
For the treatment of severe Gram-negative infections, gentamicin, an aminoglycoside antibiotic, is used. Its utility, however, is constrained by its nephrotoxicity. To prevent or decrease tissue injury, tadalafil, a selective phosphodiesterase-5 inhibitor, has been reported. The goal of this study is to determine the possible protective effects of tadalafil on rat nephrotoxicity induced by gentamicin. Twenty- four adult male Albino rats weighting 100-200 gm rats were divided into four groups (six rats each): Group1 (Control untreated): Rats received distilled water (5ml/kg, P.O) for 12 days and on days 6-12, they received (5ml/kg, i.p) of normal saline daily one hour after oral administration of distilled water. Group2 (Tadalafil group): Rats were given tadalafil (5mg/kg, P.O) for 12 days and on days 6-12, they received (5ml/kg, i.p) of normal saline daily one hour after oral administration of tadalafil. Group3 (Gentamicin group): Rats were given distilled water (5ml/kg, P.O) and on days 6-12, they received gentamicin (10 mg/kg, i.p) one hour after oral administration of distilled water. Group4 (Gentamicin+Tadalafil group): Rats were given tadalafil (5mg/kg, P.O) for 12 days and on days 6-12, they received gentamicin (100mg/kg, i.p.) one hour after oral administration of tadalafil.
In gentamicin-intoxicated rats, administration of tadalafil resulted in a nephroprotective effect as it significantly reduced serum creatinine and urea, urinary albumin, urinary albumin/creatinine ratio, renal cortex MDA and urinary KIM-1 and renal cortex NO cotent, with concomitantly increased
urinary creatinine, renal catalase, and superoxide dismutase activity compared to gentamicin group.
In addition, immunohistochemical analysis showed that tadalafil treatment significantly decreased the expression of inducible nitric oxide synthase (iNOS), whereas endothelial nitric oxide synthase (eNOS) expression was significantly enhanced. Tadalafil’s protective effects have been histopathologically confirmed.
In conclusion, treatment with tadalafil attenuates gentamicin nephrotoxicity in rats partially by improving oxidative stress by preserving catalase and superoxide dismutase activity and inhibiting malondialdehyde in the renal cortex, as well as by inhibiting iNOS expression and inducing eNOS development.
In order to be able to fully investigate the protective effect of tadalafil on gentamicin nephrotoxicity, further studies with different doses and for a longer period of tadalafil and a larger sample size are required. More studies aimed at the side effects of tadalafil should also be done.