Nicorandil pretreatment attenuates testicular ischemia–reperfusion injury in rats

Testicular torsion-detorsion is primarily characterized by ischemia-reperfusion (IR) injury, which leads to oxidative stress, Calcium overload, cell death, and disrupted spermatogenesis. Nicorandil has been shown to reduce intracellular calcium and reactive oxygen species formation, thereby limiting oxidative damage and apoptosis. This study aimed to evaluate the protective effects of nicorandil pretreatment against testicular IR injury Twenty-four male Wistar albino rats were divided into healthy control group (HC), sham-operated group (SOG), testicular IR group (TIR), and nicorandil+TIR group (N+TIR). The N+TIR received oral nicorandil (6 mg/kg) 1 hour before IR. IR was induced in the left testes (4 h ischemia, 4 h reperfusion), followed by biochemical, histopathological, and immunohistochemical evaluations. In the TIR, compared with HC, malondialdehyde (MDA) was increased, whereas total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) were decreased ( p < 0.001). Testicular IR-induced a marked decrease in serum testosterone and severe histopathological degeneration ( p < 0.001). Moreover, 8-OHdG and cleaved caspase-3 immunoreactivities were significantly increased in the TIR group ( p < 0.001). Nicorandil pretreatment suppressed testicular IR-induced MDA elevation, prevented decreases in tGSH, SOD, CAT, and testosterone levels, reduced histopathological damage, and attenuated 8-OHdG and cleaved caspase-3 immunoreactivities ( p < 0.05). Nicorandil pretreatment attenuated testicular IR-related oxidative, antioxidant, histopathological, and apoptotic alterations in rats.