The effects of rolipram, a phosphodiesterase 4 enzyme inhibitor, on testicular ischemia reperfusion injury in rats

In this study, the effects of phosphodiesterase 4 (PDE 4) enzyme inhibitor rolipram on sperm count, motility and histopathological damages in rat testes after testicular torsion/detorsion (T/D) in rats were investigated through apoptotic pathways and proinflammatory cytokines which are thought to have contributions to the damage. Rats were divided into 4 groups as Sham, rolipram (ROL), T/D and ROL+T/D. Torsion was formed by rotating the spermatic cord of the right testes of anesthetized rats 7200 clockwise and fixing it to abdomen for 3 hours. Fifteen minutes before detorsion, rolipram (single dose 10 mg/kg) or vehicle was administered intraperitoneally (i.p.) to the rats. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels and spectrophotometric caspase-3 activity in testicular tissues were measured 4 and 24 hours after detorsion. Twenty four hours after detorsion, histopathologic tissue damages and activities of caspase-3, 8 and 9 using immunohistochemical staining method were evaluated. On the 65th day of detorsion, sperm count and motility were evaluated. T/D caused significant increase in caspase-3 activity at 4th and 24th hours of detorsion, significant histopathologic damage and strong immunostaining for caspase-3 and caspase-9 in spermatogonia at 24th hours of detorsion, significant decrease in sperm count and motility at 65th day of detorsion in ipsilateral testes. Rolipram treatment significantly increased TNF-α and IL-1β levels in the T/D group. Rolipram didn't restore increased caspase-3 tissue activity, caspase-3 and caspase-9 immunostaining in germ cells, histological damage, sperm count and motility reductions associated with T/D. In conclusion, rolipram treatment increased the levels of proinflammatory cytokines in T/D injury, didn't inhibit the active intrinsic apoptotic pathway and showed no protective effects on histopathological damages and sperm count and motility.