Protective effects of sinomenine against testicular ischemia/reperfusion injury: Biochemical, histological, and immunohistochemical evidence

In testicular ischemia and reperfusion (T/IR) injury, a urological emergency that necessitates immediate intervention and treatment and may result in infertility, the study sought to determine the protective benefits of sinomenine (SIN). Thirty male Wistar albino rats were randomly separated into three groups (n=10 per group): sham, T/IR, and T/IR + SIN. Biochemical analyses were performed on testicular homogenates. Rats in the T/IR group experienced reperfusion for two hours after two hours of ischemia. The T/IR+SIN group received an intraperitoneal injection of 10 mg/kg SIN 30 min before reperfusion and underwent the same surgical procedures as those in the T/IR group. SIN demonstrated anti-inflammatory activity by increasing IL-10 levels while lowering TNF-α, IL-1β, IL-6, NGAL, and NF-κB. SIN also increased levels of antioxidant biomarkers (TAS, GSH, CAT) and decreased the levels of oxidant biomarkers (MDA, MPO, OSI, TOS, NGAL, IMA), exhibiting a protective effect against oxidative stress. Histopathological data showed protection in testicular histoarchitecture, characterized by improved epithelial disorganization, reduced severe necrosis in seminiferous tubules, decreased neutrophil infiltration in intertubular areas, and alleviation of severe edema and hemorrhagic areas. Additionally, it had a protective effect on testicular tissue against DNA damage and apoptosis by reducing the levels of 8-OHdG and caspase-3. Through its antioxidant and anti-inflammatory actions, SIN mitigated T/IR damage by limiting apoptosis and preserving normal testicular tissue structure.