The investigation of the protective effect of WNT/β-catenin signal pathway inhibitor niclosamide on diabetic erectile dysfunction

Diabetes-induced erectile dysfunction (ED) is a common complication in diabetic men. The pathogenesis of diabetic ED involves vascular and neurological factors and their mechanisms have not yet completely elucidated. Wnt/β-catenin signaling pathway has been implicated in some complications of diabetes, but the role of the Wnt/β-catenin signaling pathway in diabetic ED has not yet been identified. The aim of this study was to investigate the role of Wnt/β-catenin signaling pathway in diabetic ED and the effect of niclosamide (NZ), an inhibitor of this pathway, on erectile function in diabetic rats. Type 1 diabetes was induced in male Sprague–Dawley rats (8-10 weeks old) by streptozotocin (75 mg/kg, intraperitoneally). After 8 weeks, diabetic and nondiabetic rats were treated with NZ (10 mg/kg), NZ (25 mg/kg), XAV939 (Wnt signaling inhibitor,1 mg/kg) or vehicle for 4 weeks. All drugs were administered intraperitoneally. At week 12, intracavernous pressure (ICP) was measued, maximum ICP/mean arterial blood pressure (mICP/MAP) and total ICP/MAP ratios were calculated. Expression levels of active β-catenin, p-GSK3β, DKK1, fibronectin and procaspase-3 in penis and/or major pelvic ganglia (MPG) were evaluated by western blot. A siginificant reduction was observed in mICP/MAP and total ICP/MAP values in vehicle-treated dibatic rats, which was prevented by the treatment with NZ (10 mg/kg). In vehicle treated diabetic rats, active β-catenin and p-GSK3β expressions were decreased in the penis, while no change was observed in MPG. NZ or XAV939 did not cause any change in expression level. Fibronectin expression was increased in diabetic rat penis, which was decreased by the treatment with NZ (10 mg/kg). Procaspase-3 expressions in MPG did not differ among groups. To our results, Wnt /β-catenin signaling pathway was inhibited in diabetic rat penis and treatment with NZ at 10 mg/kg improves erectile function in diabetic rats possibly by its antifibrotic effect through Wnt/β-catenin-independent pathways.