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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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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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