Novel insights of Wnt/β-catenin/eNOS pathway and potassium channel in alleviation of testicular ischaemic injury by nicorandil in rats

Testicular ischaemia is a remarkable urological health problem affecting young males and needs immediate surgical intervention. Its incidence is about 4.5 in 100,000 males aged from 1–25 years. Finding more ameliorative medical treatment becomes mandatory to mitigate the harmful effects of testicular ischaemia reperfusion (TIR). This directed us to evaluate for the first time the impact of nicorandil (NIC) in TIR induced testicular and cardiac damage. We divided the Wistar albino rats into five groups; Sham, untreated TIR, treated TIR+NIC, TIR+NIC + ω-nitro-l-arginine (L.NNA), TIR+NIC+glimepiride (GLP). Interestingly, NIC succeeded to ameliorate TIR induced biochemical and histopathological changes. Compared to TIR, NIC increased serum testosterone by 3.9-fold and decreased cardiac troponin I 1.9-fold, CK-MB 2.4-fold, and LDH 1.3-fold. Testicular malondialdehyde (MDA) was diminished by 2.4-fold, and reduced glutathione (GSH) increased 3.1-fold. Cardiac MDA decreased 2.1-fold, and GSH rose 2.9-fold. NIC also reduced nuclear factor kappa B (NF-κB) (cardiac 1.8-fold; testicular 2-fold) and increased VEGF-A (cardiac 2.1-fold; testicular 2-fold). L.NNA or glimepiride reversed these effects (p < 0.05). NIC mitigates TIR-induced testicular and cardiac damage via the K_ATP channel opening, eNOS enhancement, and Wnt/β-catenin regulation. NIC may be a future medical therapy alongside surgery for TIR.