Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n=18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D]+saline) and group 4 (T/D+300mgkg(-1) metformin). Testicular torsion was achieved by rotating the right testis 720 degrees in a clockwise direction for 1hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4hr after detorsion (p<.001). In six rats of each group 24hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.