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Anti-inflammatory and Hepatoprotective Effects of Quercetin in an Experimental Model of Rheumatoid Arthritis

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Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the joints. Although methotrexate (MX) is the first-line treatment, side effects are common. This study aimed to investigate the effects of quercetin (QT) and/or MX on inflammation and systemic toxicity in a rat model of RA. Male Wistar rats were divided into control (C), RA, QT, MX, and QT + MX groups (n=6). The RA induction consisted of three intra-articular injections of methylated bovine serum albumin (1×/week) in the temporomandibular joint (TMJ). QT (25 mg/kg) and/or MX (0.75 mg) administration occurred by oral gavage daily. We performed mechanical hyperalgesia in TMJ, leukocyte recruitment in synovial fluid, histopathology, and immunohistochemistry (TNF-α, IL-17, and IL-10) in synovial membrane and toxicity parameters. The RA showed a reduction in the nociceptive threshold (p<0.001), increase in leukocyte recruitment in synovial fluid (p<0.001), intense inflammatory infiltrate (p<0.001), and intense immunoexpression of TNF-α, IL-17, and IL-10 in the synovial membrane (p<0.001) compared to C (p<0.001). QT and/or MX therapy reduced inflammatory parameters (p<0.001). However, downregulation of IL-10 was observed only in the groups that received MX (p<0.001). Leukocytosis was seen in RA (p<0.05), but QT and/or MX reversed it (p<0.05). MX was associated with pathological changes in the liver and higher levels of transaminases when compared to the other groups (p<0.05). QT co-administered with MX reversed this hepatotoxicity (p<0.05). There were no alterations in the kidney between the groups (p>0.05). QT has potential to support MX therapy, showing anti-inflammatory and hepatoprotective effects in this model.

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Acknowledgements

The authors gratefully acknowledge the Nucleus of Studies in Microscopy and Imaging Processing (NEMPI) and the Laboratory of Inflammation and Cancer (LAFICA) of Federal University of Ceará.

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Authors and Affiliations

  1. Department of Clinical Dentistry, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza, Brazil

    Ana Carolina de Figueiredo Costa, Joana Maria dos Santos Alves, Paula Goes, Karuza Maria Alves Pereira, Ana Paula Negreiros Nunes Alves & Delane Viana Gondim

  2. Department of Morphology, Faculty of Medicine, Federal University of Ceará, Rua Delmiro de Farias, S/N, Rodolfo Teófilo, CEP, Fortaleza, 60430-170, Brazil

    Luane Macedo de Sousa, Karuza Maria Alves Pereira, Mariana Lima Vale & Delane Viana Gondim

  3. Department of Pathology and Legal Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

    Paula Goes

  4. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

    Mariana Lima Vale

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  1. Ana Carolina de Figueiredo Costa
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Contributions

A.C.F.C., L.M.S. and J.M.S.A. performed animal and laboratory experiments. A.C.F.C., L.M.S., K.M.A.P., A.P.N.N.A., P.G and D.V.G contributed to data analysis and interpretation. A.C.F.C. wrote a draft of the manuscript. D.V.G and M.L.V. contributed to the concept and design of the study. D.V.G coordinated the experiments and critically reviewed the manuscript.

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Correspondence to Delane Viana Gondim.

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The experimental procedures were approved by the Ethical Committee on Animal Use (CEUA) of the Federal University of Ceará, Brazil with number protocol 148/17, according with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications no 8023, revised 1978) and the ARRIVE guidelines UK.

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Costa, A.C.d.F., de Sousa, L.M., dos Santos Alves, J.M. et al. Anti-inflammatory and Hepatoprotective Effects of Quercetin in an Experimental Model of Rheumatoid Arthritis. Inflammation 44, 2033–2043 (2021). https://doi.org/10.1007/s10753-021-01479-y

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