(224) Long-Acting DPP-4 Inhibitors Mitigate Vincristine-Induced Erectile Dysfunction via Vascular and Anti-Inflammatory Pathways in Rats

Introduction Late-onset complications following chemotherapy have become an increasingly important clinical issue. Through a large-scale adverse event database analysis, we previously identified potential causative agents and reported in Andrology that vincristine (VCR) caused erectile dysfunction (ED) in rats. Objective In this study, we aimed to develop a novel therapeutic approach for VCR-induced ED by investigating the efficacy of DPP-4 inhibitors. Methods Twelve-week-old male Wistar-ST rats were administered VCR intravenously at a dose of 0.1 mg/kg once a week for four weeks to create the VCR group. A Control group received intravenous saline injections via the tail vein. Two additional groups received VCR along with either trelagliptin (TGP; 3 mg/kg) or omarigliptin (OGP; 3 mg/kg), administered orally once weekly, forming the VCR+TGP and VCR+OGP groups, respectively. Erectile function was assessed at 4 and 8 weeks using intracavernosal pressure (ICP) measurements under cavernous nerve electrical stimulation, normalized by mean arterial pressure (ICP/MAP). Penile corpus cavernosum tissue was also collected for evaluation of mRNA expression of sexual function–related factors via real-time PCR. Results At 4 weeks, ICP/MAP in the VCR group (0.42 ± 0.04) was significantly lower than that in the Control group (0.72 ± 0.05, p < 0.01). However, the VCR+TGP group (0.64 ± 0.02) showed a significant improvement in ICP/MAP (p < 0.05), while no significant change was observed in the VCR+OGP group (0.50 ± 0.08, p > 0.05). By 8 weeks, the VCR+OGP group also showed a significant improvement (0.66 ± 0.10, p < 0.05). Real-time PCR analysis revealed increased expression of VEGF, MCP-1, and catalase, along with decreased IL-6 expression in both the VCR+TGP and VCR+OGP groups. Conclusions These results suggest that long-acting DPP-4 inhibitors may improve VCR-induced ED. Both TGP and OGP were associated with enhanced expression of angiogenic and antioxidant factors, and reduced expression of inflammatory cytokines. Our findings indicate that long-acting DPP-4 inhibitors could be a promising therapeutic option for managing ED caused by vincristine. Disclosure No