European Journal of Pharmacology, cilt.1001, 2025 (SCI-Expanded)
Radical prostatectomy can lead to nerve injury-related erectile dysfunction (ED). Hydrogen sulfide (H2S) is an endogenous gasotransmitter that has a role in erectile physiology. Adipose-derived stem cells (ADSCs) can serve as a valuable cell source for treating degenerative disorders. We aimed to determine the possible constructive effects of H2S donor, sodium hydrogen sulfide (NaHS), and transplantation of ADSCs per se and their combination treatment on bilateral cavernous nerve transection (CNT)-induced ED. Sprague-Dawley rats were divided into five groups: Sham-operated, CNT, CNT-treated with NaHS, CNT-treated with ADSCs and CNT-treated with NaHS and ADSCs groups. In vivo erectile responses, in vitro relaxant and contractile responses of corpus cavernosum were calculated. Protein expression and localization of nitric oxide synthases (NOS), H2S synthesis enzymes, fibrosis, and hypoxia markers as well as the smooth muscle/collagen ratio were analyzed. Rats with CNT exhibited significant decreases in erectile responses, acetylcholine and electrical field stimulation (EFS)-induced relaxation, phenylephrine and EFS-induced contractile responses of the corpus cavernosum, when were moderately increased by NaHS or ADSCs treatments alone. The combination therapy significantly improved the reduction. All treatment regimens improved decreases in NOS and H2S synthesis enzymes protein expression, smooth muscle-to-collagen ratio and increases in hypoxia and fibrosis markers in rats with CNT. The combination treatment of NaHS and ADSCs was more effective than monotherapies in improving CNT-induced ED. H2S and cell-based treatment may synergistically affect ED via regulation of molecular targets and modification of penile structure. The findings substantiate the use of a comprehensive therapeutic strategy to enhance clinical outcomes in instances of ED resulting from radical prostatectomy.