CLINICS 2011;66(1):137-142 decrease in the diameters of seminiferous tubules, GCLT and Johnsen’s testicular score (not statistically significant). However, administration of high-dose sildenafil citrate to rats in group 4 imposes a protective effect on testicular I/R injury when compared with group 2. Similarly, in a study by Kolettis et al.,33 beneficial actions on left ventricular function were evident after a low-dose of sildenafil (0.7 mg/ kg) administration to rats 30 min before myocardial ischemia, but were lost after doubling the dose (1.4 mg/ kg), and compared with controls post-ischaemic recovery was higher after low dose and unchanged after high dose. In addition, low concentrations of sildenafil improved recov- ery of reperfusion aortic output and infarct size, while high concentrations worsened aortic output recovery.34 Findings obtained in group 4 were in agreement with the results of other researchers.33,34 Since increasing level of NOS expression leads to excessive NO production, high concentrations of NO, which is an important free radical, may cause DNA damage and cell death in testis. NO increases the level of cyclic guanosine monophosphate, which results in relaxation of the smooth muscle, creating increased blood flow. Also, NO is a potent inhibitor of nicotinamide adenine dinucleotide phosphate oxidase expression in vascular tissue.35 The increased expressions of endothelial NOS and inducible NOS in I/R damage of testis has been reported previously.32 In the present study, tissue NO levels in contralateral testis were higher in group 2 than in group 1. Contralateral testis injury after UTT may be due to increased tissue NO levels. Similarly, Ust u¨n et al.29 found significant elevations in endothelial NOS and inducible NOS levels in testicular tissues after I/R damage. These authors showed that oral administration of sildenafil and vardenafil (0.5 mg/day) significantly increased endothelial NOS and inducible NOS expressions in ipsilatreal testis, and they had no protective effect on testicular I/R injury. In contrast, Erol et al.12 reported that vardenafil treatment significantly reduced endothelial NOS and inducible NOS levels in testicular tissues after I/R injury. This effect of vardenafil was shown to be mediated by increased intracellular cyclic guanosine monophosphate levels and activation of mitochondrial KATP channels either directly or through a variety of signaling pathways, such as activation of protein kinase C.36 In the present study, the tissue NO level in the contralateral testis in group 3 was significantly lower than in groups 2 and 4. In other words, the level of NO in group 1 was similar to those of group 3. These results indicate the beneficial effects of intraperitoneal low-dose sildenafil administration on I/R damage after UTT. Therefore, our findings are consistent with those of Erol et al.12 However, our results contradict those reported by Ustun et al.29 The differences may be due to oral administration of phosphodiesterase type 5 inhibi- tors. Sildenafil acts by inhibiting phosphodiesterase type 5 activity, which by preventing the hydrolysis of cyclic guanosine monophosphate increases the nucleotide, thus amplifying the effect of diminished NO.37 A possible cause of the testicular damage due to T/D is I/ R injury attributed to neutrophil infiltration and reactive oxygen species.38 Peroxidation of the lipids in membranes changes membrane permeability or disrupts membrane integrity and thus inflicts significant injury on cellular organisms.39 However, the protective role of antioxidant enzymes such as CAT, GSH and GPx against free radical attack is in balance under normal conditions. In our study, Protective effect of sildenafil citrate on contralateral testis injury Yıldız H et al. we observed that the level of tissue MDA was increased (not statistically significant) and GPx and CAT activites and GSH level were significantly decreased in group 2. Previous studies have shown similar findings that I/R injury leads to increased MDA and inactivation of antioxidant enzymes in rat testis.11,12,15 Intraperitoneal treatment with sildenafil or vardenafil prevented a further increase in MDA levels and significantly increased GSH levels and the GPx and CAT activities after testicular T/D.11,12,15 The increase in CAT values of red blood cells after sildenafil treatments has been attributed to the inhibition of free radicals and lipid peroxidation.37,40 In the curret study, the treatment of low- dose sildenafil before detorsion increased GSH levels and GPx and CAT activites (not statistically significant) and decreased the MDA level in the contralateral testis when compared with group 2, but administration of high-dose sildenafil did not cause significant improvement in these parameters. The protective effect of sildenafil citrate on oxidative stress has previously been shown in many investigations related to I/R injury in other tissues, for example in the liver, colon and brain.13–15 This effect of sildenafil could be associated with its inhibiting effect on the production of lipid peroxidation via the activity and expression of nicotinamide adenine dinucleotide phos- phate-oxidase.37,40 CONCLUSIONS I/R injury may occur in the contralateral testis following the 2-h T/D procedure. Intraperitoneal treatment of low- dose sildenafil citrate decreased free radical formation and increased antioxidant enzyme values and attenuated histo- pathological damage in the testis after T/D. Whereas, high- dose sildenafil treatment had no effect. From these results, we suggest that low-dose sildenafil, which is safe in humans, could be used to prevent lesion on the contralateral testis before surgery. REFERENCES 1. Vısser AJ, Heyns CF. 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