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Ebselen, an Active Seleno-Organic Compound, Alleviates Articular Cartilage Degeneration in a Rat Model of Knee Osteoarthritis

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Abstract

Osteoarthritis (OA) is a prevalent articular disease mainly characterized by extracellular matrix degradation, apoptosis, and inflammation, which lead to cartilage destruction and abnormal bone metabolism. With undesirable side effects, current limited symptomatic treatments are aimed at relieving pain and improving joint mobility in patients with OA. Intra-articular (IA) hyaluronic acid (HA) injection, as a nonsurgical therapy, is commonly used in the clinical management of knee OA, but the efficacy of this therapeutic option remains controversial. Ebselen has tremendous pharmacological importance for some diseases due to its antioxidant, antiapoptotic, and anti-inflammatory features. However, there is no research examining the therapeutic effect of Ebselen in OA using the rat OA model. Therefore, we aimed to investigate the therapeutic effect of Ebselen on cartilage degeneration and its role in bone morphogenetic protein 2 (BMP2) and nuclear factor kappa B (NF-κB) signaling in the molecular pathogenesis of OA. We induced a knee OA model in rats with an IA injection of monosodium-iodoacetate (MIA). After the treatment of Ebselen, we evaluated its chondroprotective effects by morphological, histopathological, and immunohistochemical methods and an enzyme-linked immunosorbent assay. We report for the first time that Ebselen treatment alleviated articular cartilage degeneration in the rat knee OA model and reduced MIA-induced BMP2 and NF-κB expressions. In addition, our results unveiled that Ebselen decreased IL-β and IL-6 levels but did not affect COMP levels in the rat serum. Ebselen could be a promising therapeutic drug for the prevention and treatment of OA by alleviating cartilage degeneration and regulating BMP2 and NF-κB expressions.

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Data Availability

The data obtained after analysis in the current study can be obtained from the relevant authors upon reasonable request.

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Funding

The present study is financially supported by the Scientific Research Project Fund of Hatay Mustafa Kemal University under project number: 19M047.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Department of Physiotherapy and Rehabilitation-Faculty of Health Sciences, Sakarya University of Applied Sciences, Sakarya, Turkey

    Hamza Malik Okuyan

  2. Department of Surgery, Faculty of Veterinary Medicine, Hatay Mustafa Kemal University, Hatay, Turkey

    Ziya Yurtal

  3. Department of Emergency and Disaster Management, School of Health, Tekirdağ Namık Kemal University, Tekirdag, Turkey

    İhsan Karaboğa

  4. Department of Molecular Biochemistry and Genetics, Graduate School of Health Sciences, Hatay Mustafa Kemal University, Hatay, Turkey

    Filiz Kaçmaz

  5. Department of Orthopedics and Traumatology, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey

    Aydıner Kalacı

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  1. Hamza Malik Okuyan
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  4. Filiz Kaçmaz
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Contributions

H.M.O., Z.Y. and A.K. designed the study. H.M.O., Z.Y., I.K. and F.K. carried out experiments. H.M.O., Z.Y., I.K. and A.K. wrote the manuscript and interpreted the results. H.M.O., Z.Y., I.K., F.K. and A.K. conducted statistical analyses, prepared graphs and revised the paper. All the authors of the paper have contributed to the present study and approved the final version of this manuscript.

Corresponding author

Correspondence to Hamza Malik Okuyan.

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Ethics Approval

The animal care and experimental protocol in the present study were approved by the local Animal Ethics Committee of Hatay Mustafa Kemal University (Approval number: 2020/04–15).

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Okuyan, H.M., Yurtal, Z., Karaboğa, İ. et al. Ebselen, an Active Seleno-Organic Compound, Alleviates Articular Cartilage Degeneration in a Rat Model of Knee Osteoarthritis. Biol Trace Elem Res 201, 3919–3927 (2023). https://doi.org/10.1007/s12011-022-03472-4

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  • DOI: https://doi.org/10.1007/s12011-022-03472-4

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