Pirfenidone and pentoxifylline attenuate acute cavernosal ischaemia–reperfusion injury in an experimental model of ischaemic priapism

Abstract Background Ischaemic priapism is a urological emergency in which sustained cavernosal veno-occlusion produces progressive hypoxia, acidosis, smooth muscle compromise, and ultimately corporal fibrosis. Cavernosal injury is not confined to the ischaemic phase, as reperfusion following detumescence may further amplify tissue damage through oxidative stress, inflammatory activation, and endothelial dysfunction; adjunctive pharmacological strategies targeting this early reperfusion phase remain insufficiently characterised. This study was designed to evaluate and compare the acute effects of pirfenidone, pentoxifylline, dexpanthenol, and selected combination regimens on biochemical and histopathological markers of cavernosal injury in a rat model of ischaemic priapism-related ischaemia–reperfusion injury. Methods Sixty-eight adult male Wistar albino rats were randomly allocated into seven groups: Sham, Control/IRI, pirfenidone, pentoxifylline, dexpanthenol, pirfenidone+dexpanthenol, and pentoxifylline+dexpanthenol. Ischaemic priapism was induced using a vacuum-assisted constriction-band model followed by a one-hour reperfusion period. Serum IL-1β, IL-10, malondialdehyde, and endothelial nitric oxide synthase levels were measured, and cavernosal tissues were evaluated by semi-quantitative histopathological scoring. Group comparisons used parametric or non-parametric tests with multiplicity adjustment. The study protocol was approved by the Animal Experiments Local Ethics Committee of Necmettin Erbakan University KONÜDAM Experimental Medicine Application and Research Center (22 December 2023; No. 2023-060). All procedures complied with institutional animal-care guidelines, and the study is reported in accordance with ARRIVE 2.0. Results Sixty-seven animals were included in the final analysis. Relative to the Sham group, the Control/IRI group exhibited significantly elevated IL-1β, IL-10, malondialdehyde, and endothelial nitric oxide synthase levels alongside marked histopathological injury, confirming successful model induction. Pirfenidone significantly attenuated IL-1β and malondialdehyde levels and improved the composite pathology score. Pentoxifylline significantly reduced IL-1β, IL-10, malondialdehyde, and endothelial nitric oxide synthase levels and similarly improved the composite pathology score. Dexpanthenol attenuated malondialdehyde levels but did not consistently improve endothelial nitric oxide synthase or overall histopathological injury. Combination regimens produced endpoint-specific effects without consistently surpassing the corresponding monotherapies. Conclusions Pirfenidone and pentoxifylline attenuated selected biochemical and histopathological components of acute cavernosal ischaemia–reperfusion injury in this experimental model. These findings are hypothesis-generating; additional studies incorporating long-term erectile function assessment, fibrotic remodelling markers, and pharmacokinetic evaluation are warranted to clarify the translational relevance.