Sequential administration of febuxostat and vitamin E protects against testicular ischemia/reperfusion injury via inhibition of sperm DNA damage in Wistar rats
摘要
The pathway of testicular ischemia–reperfusion injury (TIRI) has been shown to involve reactive oxygen species (ROS) generation in the ischemic phase and later phase of reperfusion. This study was therefore designed to investigate the effect of blockage of ROS in the ischemic and reperfusion phases of TIRI. Thirty male Wistar rats were grouped into five groups (n = 6 rats each): sham, torsion + detorsion (TD), febuxostat (FEB)-administered (TFD) group, vitamin E (V)-administered (TDV) group, and FEB and vitamin E–administered (TFDV) group. Blood samples (for inflammatory and hormonal assay), testicular (for oxidative stress and histopathology), and epididymal (for sperm DNA damage and indices) tissues were collected after 3 days of detorsion. The TFD and TFDV groups showed a significant reduction in XO and MDA (p < 0.001; η2 > 0.7), as well as a concomitant increase in CAT, thiols, and SOD levels when compared with the TD group (p < 0.01, η2 > 0.5). The TFD group significantly reduced all inflammatory markers (p < 0.05; η2 = 0.75). The observed increase (p < 0.05; η2 = 0.92) in LH level, in response to a low level of testosterone in the TD group, was significantly raised in TFD and TFDV groups. The observed decrease (p < 0.001) in inhibin level in the TD group was raised (p < 0.05; η2 = 0.90) in the TDV group only. A significant increase (p < 0.001) in sperm DNA damage in the TD group was significantly reduced (p < 0.05; η2 = 0.88) in all the treatment groups while the reduced sperm viability (p < 0.01) in the TD group was increased (p < 0.05) in the TFDV group only. There was an improvement in the testicular cytoarchitecture in the TFD and TFDV groups. This study showed that sequential administration of febuxostat in the ischemic phase of TT and vitamin E in the later phase of reperfusion protects the testes against TIRI via inhibition of oxidative stress, inflammation, and sperm DNA damage.