Examining the effectiveness of nintedanib in preventing post-laminectomy epidural fibrosis in rats Sıçanlarda laminektomi sonrası oluşan epidural fibrozisi önlemede nintedanibin etkinliğini araştırma


Ocal O., Tas A., Yildirim Z., Gundogdu A. C., Selahi O., Aycan A.

Ulusal Travma ve Acil Cerrahi Dergisi, vol.32, no.5, pp.519-526, 2026 (SCI-Expanded, Scopus, TRDizin)

  • Publication Type: Article / Article
  • Volume: 32 Issue: 5
  • Publication Date: 2026
  • Doi Number: 10.14744/tjtes.2025.33789
  • Journal Name: Ulusal Travma ve Acil Cerrahi Dergisi
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.519-526
  • Keywords: Epidural fibrosis, hydroxyproline, inflammation, myeloperoxidase, nintedanib
  • Kütahya Health Sciences University Affiliated: Yes

Abstract

BACKGROUND: In this rat model study, we examined the effects of topical and systemic nintedanib treatment on the development of post-laminectomy epidural fibrosis. METHODS: Thirty-two rats were divided into four equal groups (n=8 per group). An L1–L2 laminectomy was performed using standard microsurgical procedures. The control group underwent laminectomy only; the sterile saline group underwent laminectomy followed by sterile saline irrigation; the topical nintedanib group underwent laminectomy followed by topical nintedanib application; and the systemic nintedanib group underwent laminectomy followed by oral nintedanib administration. The degree of fibrosis was evaluated by histological examination. Plasma levels of matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), transforming growth factor beta-1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), hydroxyproline (HYP), and myeloperoxidase (MPO) were compared among the groups. RESULTS: In the control group, two rats developed grade 2 epidural fibrosis, while six animals developed grade 3 fibrosis. The sterile saline group demonstrated a similar degree of fibrosis to the control group. In the topical nintedanib group, three, four, and one rat developed grade 1, grade 2, and grade 3 epidural fibrosis, respectively. In the systemic nintedanib group, five rats had grade 1 epidural fibrosis, whereas three rats had grade 2 fibrosis. Groups 3 and 4 showed significantly decreased plasma levels of MMP-9, IL-6, VEGF, TGF-β1, TNF-α, and HYP compared to Groups 1 and 2 (p<0.05). Plasma levels of these markers were lower in Group 4 than in Group 3; however, the difference was not statistically significant (p>0.05). Plasma MPO activity in the study groups was not altered following nintedanib treatment (p>0.05). CONCLUSION: The histological and biochemical findings of the present study indicate that nintedanib is a promising pharmacological agent for the prevention of post-laminectomy epidural fibrosis. Further studies with larger sample sizes and interval assessments are needed to clarify the effects of different dosages.