Tranexamic acid has positive effect in early period of tendon healing by stimulating the tumor necrosis factor-alpha and matrix metalloproteinase-3 expression levels
Alper Çıraklı1, Pınar Naile Gürgör2, Erdal Uzun3, Havva Erdem4, Abdullah Alper Şahin1, Orhan Baş5
1Department of Orthopedics and Traumatology, Ordu University, Faculty of Medicine, Ordu, Turkey
2Department of Histology and Embryology, Ordu University, Faculty of Medicine, Ordu, Turkey
3Department of Orthopedics and Traumatology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
4Department of Pathology, Ordu University, Faculty of Medicine, Ordu, Turkey
5Department of Anatomy, Ordu University, Faculty of Medicine, Ordu, Turkey
Keywords: Matrix metalloproteinase-3, tendon healing, tranexamic acid, tumor necrosis factor-alpha, transforming growth factor-beta
Objectives: This study aims to evaluate the effect of tranexamic acid (TXA) application in tendon healing by using its immunohistochemical effects on tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-3 (MMP-3), and transforming growth factor-beta (TGF-β) expression; and to identify if TNF-α, MMP-3, and TGF-β can be used to monitor and evaluate tendon healing or not in tenotomized rat Achilles tendons.
Materials and methods: Twelve male Wistar-Albino rats (age 6-7-month-old; weighing 300-350 g) were used in this retrospective study conducted between November 2016 and May 2017. The rats were divided into two groups with similar weights. The right legs of the rats were determined as the study group (TXA), and the left legs as the control serum physiologic (SP) group. Under anesthesia, bilateral Achilles tenotomy was performed and surgically repaired. 1 mL of TXA was applied locally for the right side and 1 mL of SP was locally applied for the left side. Half of the rats were sacrificed at the third week (right leg-TXA3, left leg-SP3) and the other half at sixth week (right leg-TXA6, left leg-SP6) and tendon samples were taken from the extremities. Immunohistochemical findings of TNF-α, MMP-3, and TGF-β were evaluated on the basis of the frequency and intensity of staining.
Results: In TNF-α and MMP-3 and TXA groups, there was a significant difference in staining compared to SP groups (p<0.05). Regarding TNF-α expression, the total index score in the TXA6 subgroup was higher than the TXA3, SP6, and SP3 subgroups (8, 7, 3, and 4, respectively). Overall scores of TNF-α showed that TXA groups had significantly higher scores when compared to SP groups (p<0.05). In addition, total MMP-3 expression scores were significantly higher in TXA groups than in SP groups, respectively; TXA3: 14, TXA6: 11, SP3: 10, and SP6: 9 (p<0.05). However, the degree of staining with TNF-α was found to be significantly lower than MMP-3 (p<0.05). Immunohistochemical reactivity was not observed with TGF-β.
Conclusion: Tranexamic acid has positive effect in early period of tendon healing by stimulating the TNF-α and MMP-3 expression levels. TNF-α and MMP-3 can be used to monitor and evaluate tendon healing.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The study was carried out with the support of Ordu University Scientific Research Projects Coordination Unit (project number: HD-1801).
We thank Yakup Ekinci and Soner Çankaya for performing the statistical analysis of this article.