الفهرس 
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Abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disorder affecting approximately 1% of people in the developed countries. Despite there is no cure for RA yet, a variety of medications are available aiming to halt the disease and decrease joint damage. Although steroidal and non-steroidal anti-inflammatory drugs as well as disease-modifying antiarthritic drugs such as MTX are used frequently in RA management, these agents are associated with many adverse drug reactions as cardiovascular and gastrointestinal side effects.
The current investigation is an experimental study designed to explore the proposed anti-inflammatory and antioxidant effects of Omega-3 fatty acids in the treatment of RA and its complementary effect in combination with the half-tested doses of the most common drugs used to treat RA such as cortisone and MTX against adjuvant-induced arthritis in rats.
Seventy adult female albino rats weighing (170-200 gm) were randomly assigned into seven groups; 10 rats in each group. group 1, control group received 0.5 ml saline only. group 2, RA untreated group, where RA was induced using a modified method of arthritis by subcutaneous injection of three doses of CFA, each 0.4 ml at three different limbs on days 1, 4, 7 for 12 days. group 3, RA group treated with omega-3 (1 g\kg\d). group 4, RA group treated with DEX (1mg\kg\d). group 5, RA group treated with MTX (1mg/kg/d). group 6, RA group treated with omega-3 (1g\kg\d) +DEX (0.5mg\kg\d). group 7, RA group treated with omega-3 (1 g\kg\d) +MTX (0.5 mg/kg/d). All drugs were freshly prepared during the experiment in the concentration required and were given to the treated groups on day 13 of RA induction and continued to day 19 using an oral syringe with a blunt curved edge to avoid injury of oral mucosa of rat and to allow proper swallowing of the drug.
Body weight and paw diameter were recorded on day 1 before RA induction, day 13 after induction of RA and at the end of the experiment on day 20, blood samples drawn for biochemical tests and knee joints of rats of different groups were removed for histopathological changes and Immunohistochemical study .
Results: Treatment with OMEGA showed some improvement in the body weight on day 20 when compared to RA group values. This improvement was significant and reached nearly to the control group values when OMEGA is combined with MTX.
Treatment with OMEGA for 7 consecutive days resulted in a significant alleviation in mean paw diameter compared to that of RA group values. On the same hand, the current results showed more alleviation in mean paw diameter in the groups treated with combined regimen (OMEGA + DEX) and (OMEGA + MTX) compared to that of the RA group with insignificant differences when compared to control group values.
Administration of OMEGA decreased significantly the elevated serum COMP level compared to RA group values. Combined treatment of OMEGA plus DEX and OMEGA plus MTX resulted in more significant decrease in the elevated COMP level compared to RA group values. Also, the results showed that the combination treatment could restore the COMP level back to normal levels.
Administration of OMEGA alone or in combination resulted in a significant decrease of the elevated serum levels of TNF-ά and IL-1B compared to values of the RA group. In addition, the present study showed normalization of IL-1B values in the group treated with OMEGA + MTX.
Groups treated with OMEGA alone or in combination showed a significant alleviation of MPO values compared to the diseased group. Besides, the level of MPO return to normal levels only in groups that treated with combination therapy.
Treatment with OMEGA alone or in combination resulted in a significant amelioration of GSH and MDA levels compared to the diseased group. Only the groups that treated with OMEGA plus either DEX or MTX showed a restoration of the oxidative markers back nearly to the normal levels.
Histopathological investigations from the arthritis group revealed a distortion and evidence of arthritis which includes a distortion of the articular cartilage and loss of its regular rounded contour. In addition, some fields showed distorted cells in the superficial layer with the appearance of empty lacunae denoting dead cells and absence of cell nest. In contrast, treatment with OMEGA, DEXA, MTX, OMEGA plus DEX and OMEGA plus MTX has ameliorated these pathological changes with a restoration of the smooth articular surface with subchondral plate of bone and hypercellularity of the articular cartilage with colonization of chondrocytes.
Immunohistochemical study showed a +ve reaction in the articular cartilage of arthritis group as the Cox-2 staining was observed in many chondrocytes with a cytoplasmic and a prenuclear pattern of expression. A positive reaction was detected in some cells in the articular cartilage as well as in the synovial membrane in both groups treated with either omega or MTX. Few cells in the articular cartilage showed a +ve reaction in groups treated with DEXA, omega plus DEXA and omega plus MTX
Conclusion: the current results showed that the combination therapy of omega-3 with half the dose of the standard treatment used in RA (MTX & DEX) exhibited the best results as it could restore most of the measured parameters back to the normal levels, as there was normalization of the body weight, paw edema, COMP, IL-1B, MDA, MPO and GSH level after treatment with combination therapy. Interestingly, it could be concluded that combination therapy potentiated the effect of a single drug suggesting different mechanisms.