•  
  •  
 

Turkish Journal of Medical Sciences

Abstract

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 (PFDTpc) 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-β1), 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-β1, 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.

Author ORCID Identifier

ÖZGÜR ÖCAL: 0000-0002-8985-2626

ZUHAL YILDIRIM: 0000-0002-2808-7860

AYŞE ÇAKIR GÜNDOĞDU: 0000-0002-2466-9417

ABDURRAHİM TAŞ: 0000-0001-5786-9063

BETÜL YAMAN: 0000-0002-5028-8044

ABDURRAHMAN ÇETİN: 0000-0002-5246-7652

GÖKHAN GÜRKAN: 0000-0003-1839-1014

ABDURRAHMAN AYCAN: 0000-0002-3794-8511

DOI

10.55730/1300-0144.6404

Keywords

Epidural fibrosis, hydroxyproline, inflammation, myeloperoxidase, pirfenidone

First Page

1588

Last Page

1597

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Download

Share

COinS