Protective effect of sildenafil citrate on contralateral testis injury Yıldız H et al. CLINICS 2011;66(1):137-142 Table 2 - Degrees of some histopathological lesions of testicular sections of rats in all groups [mild (+), moderate (++), severe (+++)]. Parameters Degeneration in germinal cells Desquamation in germinal ells Reduction in germinal cell counts Disorganization in germinal cells Interstitial oedema and capillary congestion Hemorrhage ND = not detected. Significant decreases in MSTD and GCLT (p,0.01) were observed in the testis of group 2 compared with group 1 (Table 3). MTBS value in the group 2 was decreased, although the changes were not statistically significant. Histological parameters such as MSTD and GCLT in the contralateral testis of group 3 were significantly more than the values in group 2. There were no differences between groups 2 and 4. In other words, the administration of low- dose sildenafil to rats resulted in an improvement in these histopathological parameters, whereas high-dose sildenafil did not yield an improvement, as confirmed by histopatho- logical findings in groups 2 and 4. DISCUSSION The mechannisms of contralateral testis injury after UTT has not yet been identified. Different hypotheses have been put forward to explain this phenomenon. Foe example, contralateral testicular damage leads to subclinical attacks of contralateral testicular torsion, reduced contralateral testicular blood flow, a reflex activating the sympathetic system, underlying congenital defects, release of acrosomal enzymes, immunological mechanism, free oxygen radical formation after detorsion, and overproduction of NO by activated inducible nitric oxide synthase (NOS), and alterations in the blood flow.7,23–25 In contrast, Akgur at al.2 suggested that UTT causes a decrease in the perfusion of the contralateral testis, and levels of lactic acid, hypox- anthine and lipid peroxidation were increased significantly in the contralateral testis after UTT. Pampal et al.9 said that testicular I/R injury after 2-h torsion and 2-h detorsion affects the contralateral testis, epididymis and the adjacent vas deferens. They suggested that UTT leads to infertility due to the damage on the contralateral side; this infertility can be the consequence of testicular and epididymal injury, and also of altered vas motility due to vas deferens injury after testicular I/R. In addition, Aktas et al.10 found significant increases in MDA levels and decreases in the mean seminiferous tubular diameter and germinal epithe- lial cell thickness after 2-h torsion and 2-h detorsion. In contrast, Unsal et al.26 did not find any harmful effects in the Table 3 - Mean values of seminiferous tubules diameters (MSTD), germinal cell layer thickness (GCLT) and mean testicular biopsy score (MTBS) in testis of all groups. Parameters MSTD (mm) GCLT (mm) MTBS Group 1 (n = 7) 294.00 ¡ 6.79* 6.13 ¡ 0.12* 10.00 ¡ 0.00* *{{Within rows: means with different supercript letters differ significantly (p,0.01). Date are expressed as mean ¡ SEM. Group 2 (n = 10) 256.00 ¡ 4.31{ 5.50 ¡ 0.15{ 9.50 ¡ 0.22*{ 140 Group3 (n = 10) 283.83 ¡ 5.44* 6.18 ¡ 0.16* 9.66 ¡ 0.21* Group 4 (n = 10) 267.50 ¡ 6.32{ 4.87 ¡ 0.34{ 9.00 ¡ 0.25{ Group 1 Group 2 Group 3 Group 4 ND ND ND ND ND ND + + – + + + – – – – – – + + + + ++ ++ contralateral testis after 2-h torsion or detorsion in terms of biochemical or histological parameters. In our study, 2 h of 720˚ unilateral testicular T/D leads to significant changes in enzymatic antioxidants, lipid peroxidation and histological parameters in the contralateral testis. According to our results, in the contralateral testis of group 2, there were significant decreases in CAT and GPx activities, GSH levels, MSTD and GCLT, and an increase in NO level compared with group 1. These changes in the contralatral testis after unilateral testicular T/D were in agreement with the findings obtained by other researchers.2,9,26 In the present study, T/D caused a significant increase in disorganization, degeneration and desquamation in germ- inal cells, interstitial edema and capillary congestion, hemorrhage in the contralateral testis and also reduced the histological parameters such as MSTD and GCLT. Similar studies demonstrated that T/D creates increased capillary edema, congestion, interstitial hemorrhage and hemorrhagic infarcts in the injured testis and reduced seminiferous tubule diameter, GCLT and Johnsen’s testicular score.27,28 Some studies reported that administration of sildenafil and vardenafil during reperfusion reduced apoptotic cells and testicular necrosis.11,12 In contrast, Ust u¨n et al.29 reported that oral sildenafil and vardenafil (0.5 mg/kg) had no protective effect on testicular apoptotic cell. How- ever, in our study, we administrated sildenafil intraperi- toneally. Consistently, intraperitoneal administration of sildenafil11 and vardenafil12 results in significantly higher sildenafil and vardenafil concentrations in the testicular tissue than when administered orally. In several studies, it has been observed that administration of sildenafil and vardenafil during reperfusion after ischemia decreased the myocardial infarct size by opening mitocchondrial KATP channels in the heart.30,31 Mitochondrial KATP channel opening may prevent apoptosis, presumably by inhibiting the mitochondrial Ca2+ accumulation during ischemia.32 We propose that low-dose sildenafil administration caused a pivotal amelioration in the testicular histological view after T/D-induced I/R damage via a similar mechanism as suggested by some researchers.30,31 Also, administration of low-dose sildenafil citrate improved the T/D-induced