Özgür ÖCAL, Zuhal YILDIRIM, Ayşe ÇAKIR GÜNDOĞDU, Abdurrahim TAŞ, Betül YAMAN, Abdurrahman ÇETİN, Gökhan GÜRKAN, Abdurrahman AYCAN
Turkish Journal of Medical Sciences - 2026;56(5):1588-1597
Background/aim: To investigate the effect of topical and systemic administration of pirfenidone (PFD) on the development of postlaminectomy epidural fibrosis in a rat model. Materials and methods: A total of 32 male Wistar albino rats were randomly assigned to four equal groups (n = 8 per group). A bilateral total L1-L2 laminectomy was performed using a posterior midline microsurgical approach. The control group received only laminectomy; the sterile saline (SF) group received laminectomy followed by irrigation with sterile saline; the topical pirfenidone (PFD-Tpc) group received laminectomy followed by topical PFD application at the laminectomy site; and the systemic pirfenidone (PFD-Sys) group received oral PFD. The postoperative day-30 endpoint was selected to allow histopathological assessment of mature epidural scar tissue and dural adhesions. The degree of fibrosis was assessed histopathologically. Plasma levels of matrix metalloproteinase-9 (MMP-9), interleukin-6, vascular endothelial growth factor (VEGF), transforming growth factor beta-1 (TGF-beta1), tumor necrosis factor alpha, hydroxyproline (HYP), and myeloperoxidase (MPO) were compared among the groups. Results: In the control group, grade 2 epidural fibrosis was observed in two rats (25%), whereas grade 3 epidural fibrosis was observed in six rats (75%). The level of fibrosis in the SF group was similar to that in the control group. In the PFD-Tpc group, grade 1, 2, and 3 epidural fibrosis was observed in 25%, 50%, and 25% of the rats, respectively. In the PFD-Sys group, grade 1 epidural fibrosis was observed in four rats (50%) and grade 2 in four rats (50%); no grade 3 fibrosis was detected in this group. Plasma MMP-9 and HYP levels were significantly lower in the PFD-Tpc group compared with the control group (p < 0.05). Plasma MMP-9, VEGF, TGF-beta1, HYP, and MPO levels were significantly lower in the PFD-Sys group than in the control group (p < 0.05). Systemic PFD showed the most consistent histopathological and biochemical reduction in fibrosis-associated parameters. Conclusion: The histopathological and biochemical findings suggest that PFD, particularly via systemic administration, may attenuate postlaminectomy EF by reducing fibroproliferative activity, collagen-associated biochemical markers, angiogenic signaling, inflammatory response, and oxidative stress. PFD may be a promising pharmacological candidate for the prevention of postlaminectomy EF; however, further dose-response, pharmacokinetic, safety, and translational studies are required before clinical implementation.
