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The effect of tranexamic acid on synovium of patients undergoing arthroplasty and anterior cruciate ligament reconstruction surgery

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Abstract

Preoperative hemorrhage can be reduced using anti-fibrinolytic medicine tranexamic acid (TXA). During surgical procedures, local administration is being used more and more frequently, either as an intra-articular infusion or as a perioperative rinse. Serious harm to adult soft tissues can be detrimental to the individual since they possess a weak ability for regeneration. Synovial tissues and primary fibroblast-like synoviocytes (FLS) isolated from patients were examined using TXA treatment in this investigation. FLS is obtained from rheumatoid arthritis (RA), osteoarthritis (OA), and anterior cruciate ligament (ACL)-ruptured patients. The in vitro effect of TXA on primary FLS was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays for cell death, annexin V/propidium iodide (PI) staining for apoptotic rate, real-time PCR for p65 and MMP-3 expression, and enzyme-linked immunosorbent assay (ELISA) for IL-6 measurement. MTT assays revealed a significant decrease in cell viability in FLS of all groups of patients following treatment with 0.8-60 mg/ml of TXA within 24 h. There was a significant increase in cell apoptosis after 24 h of exposure to TXA (15 mg/ml) in all groups, especially in RA-FLS. TXA increases the expression of MMP-3 and p65 expression. There was no significant change in IL-6 production after TXA treatment. An increase in receptor activator of nuclear factor kappa-Β ligand (RANK-L) production was seen only in RA-FLS. This study demonstrates that TXA caused significant synovial tissue toxicity via the increase in cell death and elevation of inflammatory and invasive gene expression in FLS cells.

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Data are available from the corresponding author upon request.

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Funding

This study was financially supported by a grant (grant number: 4140) of the Research and Technology Council of Mazandaran University of Medical Sciences.

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Authors and Affiliations

  1. Orthopedic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Salman Ghaffari, Soroosh Fateh & Mehran Razavipour

  2. Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Fatemeh Faramarzi & Alireza Rafiei

  3. Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran

    Parisa Zafari

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  1. Salman Ghaffari
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  2. Soroosh Fateh
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Contributions

S. Gh and P. Z. contributed to overall project design. S. F. and F. F. performed the research and analyzed the data and prepared the figures. M. R and A. R. wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

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Correspondence to Parisa Zafari.

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This study was approved by the Mazandaran University of Medical Sciences (IR.MAZUMS.IMAMHOSPITAL.REC.1400.040).

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Ghaffari, S., Fateh, S., Faramarzi, F. et al. The effect of tranexamic acid on synovium of patients undergoing arthroplasty and anterior cruciate ligament reconstruction surgery. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3733–3742 (2023). https://doi.org/10.1007/s00210-023-02555-w

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