Role of cytokines as biomarkers in arthritic rats and the efficiency of diclofenac therapy in the presence of some antioxidants

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease accompanied by hyperplasia of the cartilage caused by infiltration of inflammatory cells and resulting in joint damage. Diclofenac is one of the most prospective and commercially successful drugs in the family of nonsteroidal anti-inflammatory drugs (NSAIDs) used for the treatment of rheumatoid arthritis. Curcumin, a member of the curcuminoid family of compounds has antioxidant and anticarcinogenic activities which have been attributed to its hydroxyl and methoxy groups. Quercetin is categorized as a flavonol has been shown to exert antimicrobial, antiviral, anti-inflammatory and antioxidant activities. Curcumin and quercetin are antioxidant molecules with anti- proliferative, anti-inflammatory and immunosuppressive activities. The objective of this study was to investigate the inhibitory activity of these three agents on inflammatory aspects of arthritis. This experiment was carried out on adult male albino rats and included two experiment, the first one aimed to show the changes occurred in some physiological and biochemical parameters in serum and tissue as a result of arthritis induction which was induced by injection 150 μl pristine. In the second experiment, five comparisons were made between normal control rats and another four animal groups suffering from arthritis. The 1 st group of them was injected intramuscularity with diclofenac (5mg/100g b.wt) for 1, 2 and 4 weeks. The 2 nd group was treated with diclofenac and administrated orally with 100 mg curcumin / 100 g b.wt. for 1, 2 and 4 weeks. The 3rd animal group was treated with diclofenac and administrated orally 100 mg quercetin /100 g b.wt. for the same pervious intervals. The 4th arthritic animal group treated with diclofenac, curcumin and quercetin as described before for the same times. In this study, the obtained results revealed that induction of arthritis in rats caused a significant elevation in the levels of C-reactive protein (CRP), interleukin-1α (rat IL-1α), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Also, in arthriric rats, serum total antioxidant capacity (TAC) decreased while total oxidative capacity (TOC), total antioxidant, total nitric oxide (TNO) and resistin increased. In joint cartilage of arthritic rats, prostaglandin (PGE2), cyclooxygenase (COX-2), malondialdehyde (MDA) and resistin levels were remarkably increased compared to those normal control animals. All previous parameters were corrected after the administration of diclofenac with curcumin or/and quercetin depending on the time of treatment (1, 2 & 4 weeks). The data were discussed according to available obtained researches.