HMG-CoA Reductase Inhibition Protects Testis and Sperm Quality from Testicular Ishemia and Reperfusion via Activation of Antioxidant Status and AKT Signaling

Testicular torsion (TT) is a urological emergency that results in ischemia/reperfusion (I/R) injury, leading to oxidative stress, cellular apoptosis, and impaired spermatogenesis. This study aimed to investigate the protective effects of the HMG-CoA reductase inhibitor rosuvastatin on TT-induced I/R injury and elucidate the underlying mechanisms. Male Balb/C mice (n = 28) were subjected to 720° testicular torsion for two hours, followed by 24 hours of detorsion. Rosuvastatin was administered either acutely post-torsion or prophylactically prior to injury. Histopathological analysis, oxidative stress parameters, sperm motility and morphology assessments, as well as western blot analysis of survival-related signaling proteins (pAKT, pJNK, pERK1/2, and Bcl-xL), were performed. Rosuvastatin treatment significantly reduced tissue damage decreased oxidative stress (as evidenced by increased TAS and reduced TOS/OSI), and improved sperm motility and morphology. Both treatment regimens enhanced cell survival by increasing pAKT and Bcl-xL levels and decreasing pERK1/2 activation, while also activating stress-responsive JNK1/2 signaling. These findings suggest that rosuvastatin mitigates I/R-induced testicular damage through modulation of key intracellular signaling pathways, notably PI3K/AKT, and supports its therapeutic potential in acute testicular injuries and related degenerative conditions.