الفهرس 
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Abstract
Sildenafil citrate is used to treat erectile dysfunction in men. Several studies have shown that sildenafil also offers benefits in pulmonary arterial hypertension and congestive heart failure . It inhibits phosphodiesterase-5 (PDE5), which catalyzes the breakdown of cGMP, one of the primary factors involved in smooth muscle relaxation .The effect of sildenafil citrate on renal and testicular vascular beds was not studied.
This study was carried out in order to investigate the role of sildenafil citrate in the protection against glycerol induced acute renal failure , indomethacin induced chronic renal failure and colchicine induced spermatogenic impairment . It was carried on 3 main parts , each was carried on 3 groups of adult male Sprague- Dawely rats.
In the first part, group I was control group , injected (i.m.) with 0.9% NaCl . Group II was injected with glycerol in a dose of 1 ml/100 g once (i.m.) after 15 hours of water deprivation for induction of acute renal failure. Group III was given sildenafil orally (8 mg /kg/day ) for one week before induction of acute renal failure by glycerol.
In the second part, group I was control group , injected (i.m.) with 0.9% NaCl. Group II was injected with indomethacin in a dose of 10 mg/kg/day (i.m.) for ten days for induction of chronic renal failure. Group III was given sildenafil orally (8 mg /kg/day ) for ten days together with indomethacin.
The parameters used to evaluate acute and chronic renal failure were serum urea , serum creatinine ,serum sodium ,serum potassium ,renal blood flow and histopathological changes of the kidney tissues.
In the third part, group I was control group , injected (s.c.) with 0.9% NaCl. Group II was injected with colchicine in a dose of 25 mg/kg/day (s.c.) for 25 days for induction of male infertility. Group III was given oral sildenafil (8 mg /kg/day ) for 25 days coincidently with induction of infertility by colchicine .
The parameters studied in these three groups were seminal parameters (sperm count , viability ,motility & abnormal forms ) , sexual behavior (ML , MF, IL, IF , EL , EF, PEI and ICI) , testicular blood flow and histological changes of the testicular tissue .
In the last part of this study we evaluated the effect of sildenafil on isolated rat vas deferens and on noradrenaline induced vas contractions.
The obtained results of this study could be summarized as follow:-
• Glycerol injection in a dose of 1 ml/100g once (i.m.) ; resulted in acute renal failure manifested by significant increase in serum urea, serum creatinine and serum potassium. It also caused significant decrease in renal blood flow and changes in the histological finding as compared with the control group.
• Sildenafil oral administration (8 mg /kg/day) for a week before induction of acute renal failure resulted in significant decrease in serum urea , serum creatinine and serum potassium . It also showed significant increase in renal blood flow and moderate histological changes as compared with glycerol injected group.
• Indomethacin injection in a dose of 10 mg/kg/day (i.m.) for ten day resulted in significant increase in serum urea, serum creatinine and serum potassium. It caused also significant decrease in renal blood flow and changes in the histological findings as compared with the control group.
• When sildenafil was administered in a dose of 8 mg/kg/day together with indomethacin for ten days , there is significant decrease in serum urea , serum creatinine and serum potassium with mild histological changes in renal tissues as compared with indomethacin group.
• In the third part , colchicine s.c. injection at a dose of 25 mg/kg/day for 25 days resulted in significant decrease in all sperm parameters except abnormal sperm forms which were significantly increased when compared to control group . Also there were significant changes in testicular tissue but no significant changes in testicular blood flow or sexual behavior .
• Sildenfil oral administration (8 mg /kg/day) together with colchicine for the same 25 days resulted increase in all sperm parameters relative to group II which was significant except in sperm abnormal forms. There were also significant positive effects on testicular blood flow , sexual behavior and testicular histology.
• Sildenafil caused no effects on isolated rat vas deferens or noradrenaline induced vas contractions.
from the above results we conclude that sildenafil is protective against acute tubular necrosis that may be caused by glycerol and chronic renal impairment induced by indomethacin. It may have also positive effects on sperm parameters in oligoathenozoospermic rats . We also confirmed its positive effects on sexual behavior . On the other hand , sildenafil may have no influences on the ejaculatory process evidenced by the missing effects on isolated rat vas deferens.
from previous data one may assume that (conclusions):
Sildenafil protects against glycerol and indomethacin induced renal impairment . It also has positive effects on spermatogenesis and semen production and quality , and it increases fertility .These effects of sildenafil are attributed to its vasodilator effects (positive effects on renal and testicular blood flow) of NO-cGMP signal pathway . We also confirmed the positive effects of sildenafil on sexual desire and behavior and the absent effects of the drug on the vas deferens.
Proposal for future research:
• Further studies on the effect of sildenafil in experimental animal models are needed to evaluate its role in the protection against acute tubular necrosis as the experimental trials are more controlled than human cases.
• Further investigations are needed to find out the dose dependent effect of sildenafil on renal and testicular vascular beds.
• Also more studies are needed elucidate other mechanisms of action of the protective effect of sildenafil on renal and testicular tissues.
• More studies are needed to discover how sildenafil improves the sperm production and quality, whether by increasing the level of hormones relating to sperm production or by causing a direct effect on the testes.