Combinatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells and Indomethacin on Adjuvant-Induced Arthritis in Wistar Rats: Roles of IL-1β, IL-4, Nrf-2, and Oxidative Stress

Author:

Ahmed Eman A.1ORCID,Ahmed Osama M.1ORCID,Fahim Hanaa I.1ORCID,Mahdi Emad A.2,Ali Tarek M.34ORCID,Elesawy Basem H.56ORCID,Ashour Mohamed B.1ORCID

Affiliation:

1. Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt

2. Pathology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt

3. Department of Physiology, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia

4. Department of Physiology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

5. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia

6. Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Abstract

Rheumatoid arthritis (RA) is a disorder triggered by autoimmune reactions and related with chronic inflammation and severe disability. Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) have shown a hopeful immunomodulatory effect towards repairing cartilage and restoring joint function. Additionally, indomethacin (IMC), a nonsteroidal compound, has been considered as a potent therapeutic agent that exhibits significant antipyretic properties and analgesic effects. The target of the current research is to assess the antiarthritic efficacy of BM-MSCs (106 cells/rat at 1, 6, 12 and 18 days) and IMC (2 mg/kg body weight/day for 3 weeks) either alone or concurrently administered against complete Freund’s adjuvant-induced arthritic rats. Changes in paw volume, body weight, gross lesions, and antioxidant defense system, as well as oxidative stress, were assessed. The Th1 cytokine (IL-1β) serum level and Th2 cytokine (IL-4) and Nrf-2 ankle joint expression were detected. In comparison to normal rats, it was found that the CFA-induced arthritic rats exhibited significant leukocytosis and increase in paw volume, LPO level, RF, and IL-1β serum levels. In parallel, arthritic rats that received BM-MSCs and/or IMC efficiently exhibited decrease in paw edema, leukocytosis, and enhancement in the antioxidant enzymatic levels of SOD, GPx, GST, and GSH in serum besides upregulation of Nrf-2 and anti-inflammatory IL-4 expression levels in the ankle articular joint. Likewise, these analyses were more evidenced by the histopathological sections and histological score. The data also revealed that the combined administration of BM-MSC and IMC was more potent in suppressing inflammation and enhancing the anti-inflammatory pathway than each agent alone. Thus, it can be concluded that the combined therapy with BM-MSC and IMC may be used as a promising therapeutic choice after assessing their efficacy and safety in human beings with RA, and the antiarthritic effects may be mediated via modulatory effects on Th1/Th2 cytokines, ozidative stress, and Nrf-2.

Funder

Taif University

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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