Can pirfenidone prevent tendon adhesions? An experimental study in rats
Tülin Türközü1
, Necip Güven1, Fikret Altindağ2, Abbas Tokyay3, M. Ata Gökalp1, Ulan Ismailov1, M. Ali Uyumaz1, Suna Akkol4
1Department of Orthopedics and Traumatology, Van Yüzüncü Yıl University Faculty of Medicine, Van, Türkiye
2Department of Histology, Van Yüzüncü Yıl University, Faculty of Medicine, Van, Türkiye
3Department of Orthopedics and Traumatology, Ministry of Health University Prof. Dr. Ilhan Varank Training and Research Hospital, İstanbul, Türkiye
4Department of Animal Science, Yüzüncü Yıl University, Faculty of Agriculture, Van, Türkiye
Keywords: Pirfenidone, rats, tendon adhesion, tendon healing.
Abstract
Objectives: In this experimental study, we aimed to investigate the effectiveness of oral pirfenidone (PFD) treatment on preventing tendon adhesion and tendon healing in rats.
Materials and methods: A total of 21 rats were assigned into three groups including seven rats in each group. In Group 1 (sham group), no surgical procedure was performed. In Group 2 (control group), tendon repair was performed following right achillotomy. In Group 3 (treatment group), the rats also underwent tendon repair after right achillotomy. Additionally, 30 mg/kg of oral PFD was initiated from the postoperative Day 1 and administered via gavage for 28 days. At the end of the study, tendon healing and fibrosis levels in the tendon repair site were compared macroscopically, histopathologically, and immunohistochemically among the groups.
Results: Macroscopically, moderate and severe adhesions were observed in four and three rats, respectively in the control group, while no adhesion was found in four rats and filmy adhesions were observed in three rats in the treatment group (p<0.01). Microscopically, there was moderate adhesions in three rats and severe adhesions in four rats in the control group, while three rats had no adhesions and four rats had slight adhesions in the treatment group (p<0.01). Microscopically, tendon healing was good in six rats and fair in one rat in the control group, while five rats showed excellent tendon healing and two rats showed good tendon healing in the treatment group (p<0.01). Immunohistochemically, expressions of collagen I (p<0.01), collagen III (p<0.001), vascular endothelial growth factor (VEGF) (p<0.001), and proliferating cell nuclear antigen (PCNA) (p<0.001) significantly decreased in the treatment group compared to the control group.
Conclusion: Our study results indicated that PFD decreased collagen synthesis and prevented the formation of peritendinous adhesion in rats; however, it did not impair tendon healing.
Citation: Türközü T, Güven N, Altindağ F, Tokyay A, Gökalp MA, Ismailov U, et al. Can pirfenidone prevent tendon adhesions? An experimental study in rats. Jt Dis Relat Surg 2023;34(2):396-404. doi: 10.52312/jdrs.2023.1012.
The animals were supplied from The Department of Experimental Animals Care and Production Unit of Van Yüzüncü Yıl University, and ethical approval was obtained for the the study from Animal Experiments Local Ethics Committee of Van Yüzüncü Yıl University (date: 23.12.2021, no: 2021/12-18).
Idea/concept, design/control/ supervision, writing the article: T.T.; Critical review: N.G.; Histological assesment/ analysis and/or interpretation: F.A.; Literature review: A.T.; Analysis and/or interpretation: M.A.G.; Surgical intervention/data collection and/or processing: U.İ., M.A.U.; Statistical assesment/analysis and/or interpretation: S.A.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
The data that support the findings of this study are available from the corresponding author upon reasonable request.