(691) The Protective Effect of Pirfenidone on Ischemia/Reperfusion Injury in an Experimental Rat Testicular Torsion Model

Introduction Testicular torsion represents a urological emergency characterized by ischemia/reperfusion (I/R) injury, leading to oxidative stress, inflammation, and potential impairment of spermatogenesis. Pirfenidone, a small-molecule drug with antifibrotic, anti-inflammatory, and antioxidant properties, has shown promising results in reducing I/R damage in various organs. However, its potential protective role in testicular torsion remains to be elucidated. Objective This study aimed to evaluate the protective effects of Pirfenidone on testicular I/R injury in an experimental rat model of testicular torsion. Methods A total of 21 adult male Sprague–Dawley rats were randomized into four groups: Control (n=5), Sham (n=5), Torsion/Detorsion (T+D) (n=6), and Torsion/Detorsion + Pirfenidone (PFD) (n=5). In the T/D and PFD groups, 4 hours of ischemia followed by 24 hours of reperfusion were induced. The PFD group additionally received oral Pirfenidone at a dose of 500 mg/kg, administered 30 minutes before reperfusion. For biochemical analysis, tissue samples were collected to measure malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), interleukin-1β (IL-1β), tissue inhibitor of metalloproteinase-2 (TIMP-2), and connective tissue growth factor (CTGF). Serum samples were analyzed for total antioxidant status (TAS), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), plasminogen activator inhibitor-1 (PAI-1), and matrix metalloproteinase-2 (MMP-2). Immunohistochemical staining was performed to evaluate the expression of TGF-β. Histopathological examination assessed the direct microscopic findings of the testicular tissue. Spermatogenesis was evaluated using the Johnsen score. Results Biochemical evaluation showed that IL-1β, TNF-α, TGF-β, TIMP-2, and PAI-1 levels were significantly higher in the T+D group compared to the control group (p=0.001, p=0.017, p<0.001, p=0.015, and p<0.001, respectively). Post-hoc analysis demonstrated that Pirfenidone treatment significantly reduced IL-1β and TGF-β levels compared to the T/D group (p=0.003 and p<0.001, respectively). While GSH, MPO, TOS, CTGF, and MMP-2 levels increased and TAS levels decreased in the T/D group compared with controls, the opposite trends were observed in the PFD group; however, these changes did not reach statistical significance. Immunohistochemical evaluation revealed reduced TGF-β expression in the PFD-treated group, although the difference was not statistically significant. Johnsen score comparisons among groups showed a near-significant trend without statistical significance. Conclusions Pirfenidone exhibits both anti-inflammatory and antioxidant effects against testicular I/R injury, predominantly through its anti-inflammatory activity. Further clinical studies with larger sample sizes are required to definitively determine whether Pirfenidone provides a protective effect on the testis following torsion. Disclosure No