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

**Authors:** Nilay Kaya, Emine Nur Ozbek, Nevin Ersoy, Gunay Yetik-Anacak, Serap Cilaker Micili, Ozan Bozkurt, Nergiz Durmus

PMC · DOI: 10.1007/s00345-026-06349-6 · World Journal of Urology · 2026-03-16

## TL;DR

This study shows that sodium hydrosulfide reduces tissue damage during reperfusion in a rat model of ischemic priapism.

## Contribution

The study demonstrates that systemic NaHS administration mitigates reperfusion injury in experimental ischemic priapism.

## Key findings

- NaHS increased H₂S levels and reduced HIF-1α expression in penile tissue.
- NaHS alleviated histopathological changes caused by reperfusion injury.
- Lower H₂S levels during ischemia and reperfusion were linked to penile tissue damage.

## Abstract

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.

## Linked entities

- **Proteins:** HIF1A (hypoxia inducible factor 1 subunit alpha)
- **Chemicals:** sodium hydrosulfide (PubChem CID 28015), methylene blue (PubChem CID 4139)

## Full-text entities

- **Genes:** Sdhb (succinate dehydrogenase complex iron sulfur subunit B) [NCBI Gene 298596], Cbs (cystathionine beta-synthase) [NCBI Gene 12411] {aka HIP4}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, Rho (rhodopsin) [NCBI Gene 24717], Cth (cystathionine gamma lyase) [NCBI Gene 107869] {aka 0610010I13Rik, CGL, CSE, Cys3}, Adora2b (adenosine A2B receptor) [NCBI Gene 29316], Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, Mpst (mercaptopyruvate sulfurtransferase) [NCBI Gene 246221] {aka 3MST, Mst}
- **Diseases:** IP (MESH:D011317), Alzheimer (MESH:D000544), MT (MESH:D010300), vascular congestion (MESH:D002311), erectile dysfunction (MESH:D007172), pulmonary hypertension (MESH:D006976), hypoxic (MESH:D002534), penile tissue damage (MESH:D010409), Inflammation (MESH:D007249), Desquamation (MESH:D017490), Edema (MESH:D004487), Ischemia (MESH:D007511), IR (MESH:D015427), microvascular damage (MESH:D017566), renal tubular injury (MESH:D015499), hemorrhage (MESH:D006470), injury (MESH:D014947), /R (MESH:C580424), acidosis (MESH:D000138), ischemic (MESH:D002545), muscle injury (MESH:D009135), dislocation (MESH:D004204), obese (MESH:D009765), vascular injury (MESH:D057772), corporal tissue injury (MESH:D017695), fibrosis (MESH:D005355), sickle cell anaemia (MESH:D000755), collagen (MESH:D003095), Hypoxia (MESH:D000860)
- **Chemicals:** Hematoxylin (MESH:D006416), pyridoxal phosphate (MESH:D011732), ephedrine (MESH:D004809), adenosine (MESH:D000241), eosin (MESH:D004801), PPB (MESH:D011075), Na2S (MESH:C033479), epinephrine (MESH:D004837), peroxynitrite (MESH:D030421), nitrogen (MESH:D009584), glucose (MESH:D005947), norepinephrine (MESH:D009638), saline (MESH:D012965), FeCl3 (MESH:C024555), biotin (MESH:D001710), trichloroacetic acid (MESH:D014238), BCA (MESH:C047117), zinc sulfide (MESH:C031238), NO (MESH:D009569), phenylephrine (MESH:D010656), MT (-), potassium phosphate (MESH:C013216), hydroxyl radicals (MESH:D017665), ROS (MESH:D017382), citrate (MESH:D019343), calcium (MESH:D002118), H2S (MESH:D006862), formalin (MESH:D005557), zinc acetate (MESH:D019345), L-cysteine (MESH:D003545), methylene blue (MESH:D008751), oxygen (MESH:D010100), hydrogen peroxide (MESH:D006861), urethane (MESH:D014520), metaraminol (MESH:D008680), NaHS (MESH:C025451)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** Hep3B — Homo sapiens (Human), Childhood hepatocellular carcinoma, Cancer cell line (CVCL_0326), EA hy926 — Homo sapiens (Human), Hybrid cell line (CVCL_3901), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12992350