Curcumin and Mesenchymal Stem Cells Ameliorate Ankle, Testis, and Ovary Deleterious Histological Changes in Arthritic Rats via Suppression of Oxidative Stress and Inflammation

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory condition, an autoimmune disease that affects the joints, and a multifactorial disease that results from interactions between environmental, genetic, and personal and lifestyle factors. This study was designed to assess the effects of curcumin, bone marrow-derived mesenchymal stem cells (BM-MSCs), and their coadministration on complete Freund’s adjuvant- (CFA-) induced arthritis in male and female albino rats. Parameters including swelling of the joint, blood indices of pro-/antioxidant status, cytokines and histopathological examination of joints, and testis and ovary were investigated. RA was induced by a single dose of subcutaneous injection of 0.1 mL CFA into a footpad of the right hind leg of rats. Arthritic rats were treated with curcumin (100 mg/kg b.wt./day) by oral gavage for 21 days and/or treated with three weekly intravenous injections of BM-MSCs ( 1 × 10 6 cells/rat/week) in phosphate-buffered saline (PBS). The treatment with curcumin and BM-MSCs singly or together significantly ( P < 0.05 ) improved the bioindicators of oxidative stress and nonenzymatic and enzymatic antioxidants in sera of female rats more than in those of males. Curcumin and BM-MSCs significantly ( P < 0.05 ) improved the elevated TNF-α level and the lowered IL-10 level in the arthritic rats. Furthermore, joint, testis, and ovary histological changes were remarkably amended as a result of treatment with curcumin and BM-MSCs. Thus, it can be concluded that both curcumin and BM-MSCs could have antiarthritic efficacies as well as protective effects to the testes and ovaries which may be mediated via their anti-inflammatory and immunomodulatory potentials as well as oxidative stress modulatory effects.

Diosmin and Trolox Have Anti-Arthritic, Anti-Inflammatory and Antioxidant Potencies in Complete Freund’s Adjuvant-Induced Arthritic Male Wistar Rats: Roles of NF-κB, iNOS, Nrf2 and MMPs

“…The change in paw edema has historically been used to assess an anti-inflammatory drug’s effectiveness in RA [ 34 ]. As indicated by the joint histology results in this and earlier studies, this drop in paw circumference signifies a decrease in swelling rate that can be related to a reduced edema, attenuated inflammatory processes, and reduced hyperplasia of the synovial tissue [ 14 , 15 , 16 , 17 , 18 , 49 ]. These findings could be attributed to the anti-inflammatory actions of diosmin and trolox [ 34 , 50 ].…”

“…A ruler was used to determine the length of the thread. Measurements were taken once a week after the adjuvant injection (on the 7th and 14th days) [ 16 , 18 ].…”

“…Currently, conventional drug therapies prescribed for RA have side effects, prompting a global search for new therapeutics from natural sources [ 14 , 15 , 16 , 17 , 18 ]. These side effects depend on the type, dose and time of administration of the drugs, which are steroidal anti-inflammatory drugs (SAIDs), non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs).…”

Assessment of the Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells against a Monoiodoacetate-Induced Osteoarthritis Model in Wistar Rats

“…The protocol for the isolation and culture of BM-MSCs was done according to the procedure of Ahmed et al [ 11 ] and Chaudhary and Rath [ 20 ]. BM-MSCs were flushed out of the humerus, femurs, and tibiae of the rats and centrifuged at 3000 RPM for 5 min at room temperature.…”

“…Current studies have focused on mesenchymal stem cell (MSC) therapies as they promote the protection, regeneration, and restoration of degenerated and injured joints resulting from arthritis [11][12][13]. Although the precise mechanism underlying the effectiveness of stem cell-based injectable treatments is not yet completely known [14], the capability of MSCs to migrate and engraft onto multiple musculoskeletal tissues and undergo differentiation into functional chondrocytes [15,16], regenerate meniscus [17], and produce therapeutic growth factors and cytokines [6,18] has drawn significant interest as a way to facilitate the repair of damaged tissues and halt disease progression.…”