Investigating the Effect of Sulodexide on Reperfusion Injury Through NLRP3-mediated Pyroptosis in Rats Subjected to Testicular Torsion Detorsion

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Kösa Ç., YIĞMAN Z., Yiğman M., ATALAR K., CEYHAN M. Ş., Madadzada E., ...Daha Fazla

Bratislava Medical Journal, 2026 (SCI-Expanded, Scopus)

Özet

Objective: Currently, there is no accurate medication to reduce the ischemia-reperfusion injury occurring after detorsion surgery in clinical practice. Pyroptosis has been shown to take place in testicular ischemia-reperfusion injury. Sulodexide is known for its endothelial protective and anti-thrombotic properties. The present study investigated the potential protective effects of sulodexide against ischemia-reperfusion injury in a rat testicular torsion-detorsion model, focusing on histopathological alterations, biochemical oxidative stress parameters, and immunohistochemical analysis of key markers of the NLRP3-mediated pyroptotic pathway. Methods: Rats were assigned to four groups. The left testis of rats in the Sham (S) and sulodexide (SUL) groups was exposed, and the rats were administered saline and 10 mg/kg sulodexide, respectively. After a 720° clockwise torsion was applied to the left testis of rats in the torsion-detorsion (T/D) and torsion-detorsion+sulodexide (T/D-SUL) groups, they were administered saline and 10 mg/kg sulodexide, respectively, 30 min before reperfusion. At the end of the 120-minute torsion, rats underwent a 24-hour reperfusion period, which was followed by sacrification. In addition to evaluating the NLRP3-mediated pyroptotic pathway, histopathological scoring (including the Johnsen and Cosentino scores) and biochemical analysis of oxidative stress (MDA and CAT) were performed to provide a multifaceted assessment of Sulodexide’s effects. Results: Malondialdehyde (MDA) levels were increased in the T/D group compared to the S and SUL groups (p = 0.020 and p = 0.010), whereas they were decreased in the T/D-SUL group compared to the T/D group (p = 0.045). Catalase (CAT) enzyme activity was decreased in the T/D group compared to the S and SUL groups (p = 0.042 and p = 0.013). NLRP-3, cleaved caspase-1, GSDMD-N, IL-1β, and IL-18 immunoreactivities were significantly increased in the T/D group compared to the S (p = 0.005, p = 0.002, p = 0.045, p = 0.009 and p = 0.007, respectively) and SUL groups (p = 0.003, p = 0.006, p = 0.004, p = 0.049 and p = 0.021, respectively). Conversely, NLRP-3, cleaved caspase-1, GSDMD-N, and IL-1β immunoreactivities were lower in the T/D-SUL group compared to the T/D group (p = 0.038, p = 0.005, p = 0.021 and p = 0.013, respectively). Johnsen-like score and mean diameter of seminiferous tubules were decreased in the T/D group compared to the S (p < 0.001 and p = 0.004) and SUL groups (p < 0.001 and p = 0.027), while they were increased in the T/D-SUL group compared to the T/D group (p = 0.049 and p = 0.029). Cosentino score and total injury scores were increased in the T/D group compared to the S group (p < 0.001 and p = 0.002), whereas the Cosentino score was decreased in the T/D-SUL group compared to the T/D group (p = 0.031). Conclusion: Sulodexide exhibits a potential protective role against testicular torsion-detorsion injury, which may be associated with its ameliorating effects on lipid peroxidation and on key markers of the NLRP3-mediated pyroptotic pathway. However, prospective studies are warranted to further investigate and confirm the definitive molecular mechanisms, optimal therapeutic windows, and long-term efficiency of sulodexide application.