Systemic sodium hydrosulfide (NaHS) administration mitigates reperfusion injury in an experimental model of ischemic priapism

Ischemic priapism (IP) is characterised by prolonged, painful erections that require urgent intervention to prevent corporal fibrosis and erectile dysfunction. Hydrogen sulfide (H₂S), a gaseous mediator, has been shown to exert protective effects against ischemia-reperfusion (IR) injury by reducing oxidative stress, enhancing mitochondrial function, and inhibiting apoptosis. This study aimed to investigate the role of H₂S during IP and reperfusion and its potential protective effects against penile tissue injury. Twenty-eight male Wistar rats were divided into four groups: control, IP, IP-R, and IP-[NaHS]-R. The control group underwent penectomy only. In the IP group, penectomy was performed after 4 h of priapism, whereas in the IP-R group, it was performed after 4 h of priapism followed by 1 h of reperfusion. In the IP-[NaHS]-R group, rats received NaHS (75 µmol/kg, intraperitoneally) 10 min before reperfusion. Endogenous H₂S levels were determined by the methylene blue assay, and hypoxia-inducible factor-1α (HIF-1α) expression was evaluated by immunohistochemistry. Histopathological analyses were performed to assess tissue alterations. The IP and IP-R groups showed edema, inflammation, desquamation, vasocongestion, and increased collagen deposition, and exhibited reduced H₂S levels (p < 0.05) and elevated HIF-1α (p < 0.0001) compared with control group. NaHS administration increased H₂S levels, reduced HIF-1α expression, and alleviated histopathologic changes. Decreased H₂S levels during ischemia and reperfusion were associated with penile tissue injury in IP. NaHS mitigated morphological damage during the initial phase of reperfusion, indicating the potential involvement of H₂S signaling in reperfusion-related corporal tissue injury. However, endpoints related to the resolution of priapism, such as detumescence time and intracavernosal pressure (ICP), have not been evaluated. These assessments are necessary to determine the translational safety and therapeutic applicability of these treatments in cases of IP.