الفهرس 
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Abstract
Summary & Conclusion
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease that causes functional disability. The etiology and pathogenesis of RA remain unknown but it seems likely that an autoimmune-mediated attack on the joints plays a crucial role in pathogenesis of the disease.
This study was designed to investigate the effect of caffeic acid methyl ester, pentoxifylline and pioglitazone each alone and in combination with methotrexate on rheumatoid arthritis induced experimentally in rats either by complete Freund’s adjuvant or by pristane. The effects of the studied drugs were compared with the effect of methotrexate, which was used as a reference standard in treatment of rheumatoid arthritis.
This study was divided into two models:
Model (I):
This part of study investigated the effects of the studied drugs each alone or in combination with methotrexate on complete Freund adjuvant.
Model (II):
This part of study investigated the effects of the studied drugs each alone or in combination with methotrexate on pristane.
The following results were obtained:
1- After 14 days of intradermal injection of CFA in a dose of 0.1 ml as a single dose induced a significant increase in arthritic index, ESR, serum RF level, serum CRP level, serum TNF-α level, serum nitrite level and blood SOD level and a significant decrease in blood GSH. For pristane, the intradermal administration of 0.2 ml single dose induced a significant increase, a little high than CFA, in arthritic index, ESR, serum RF level, serum CRP level, serum TNF-α level, serum nitrite level and blood SOD level, and a significant decrease, a bit high than CFA, in blood GSH level, this effects appeared after 14 days of injection.
2- In addition, both intraperitoneal injection of methotrexate in a dose of 0.25 mg/Kg daily and oral administration of pioglitazone in a dose of 3 mg/kg daily, each alone as a treatment for 2 weeks after induction of arthritis, induced a high significant decrease in arthritic index, ESR, serum RF level, serum CRP level, serum TNF-α level, serum nitrite level and blood SOD level, and a high significant increase in blood GSH level. However, methotrexate had more significant results than pioglitazone.
3- Furthermore, oral administration of caffeic acid methyl ester in a dose of 10 mg/Kg and intraperotonial injection of pentoxifylline in a dose of 150 mg/kg, daily each alone for a similar period, induced a significant decrease in arthritic index, ESR, serum RF level, serum CRP level, serum TNF-α level, serum nitrite level and blood SOD level, and a significant increase in blood GSH level.
4- Over and above, the administration of the three combinations between MTX and drugs under investigations (MTX + CM), (MTX + PTX), (MTX + Pg) after induction of RA, all elicited a significant decrease in arthritic index, ESR, serum RF level, serum CRP level, serum TNF-α level, serum nitrite level and SOD level in whole blood, and a significant increase in GSH level in fresh blood. However, Combination between MTX and Pg had more significant results, then (MTX + CM) combination comes in the second place, and at last comes (MTX + PTX) combination with the least significant ones.
from the previous results, it can be concluded that:
1. Unsurprisingly, each model of induction, either CFA or pristane, proved the efficacy of methotrexate as being the cornerstone of disease-modifying treatment in patients with RA.
2. This study revealed that all three drugs, CM, PTX and Pg, showed anti-inflammatory properties and strong antioxidant activities when administered as treatment to arthritic rats each alone or in combination with MTX.
3. The anti-inflammatory properties of these drugs were confirmed by reduction of ESR, serum RF level, serum CRP level, serum TNF-α level, serum nitrite level and blood SOD level. While antioxidant activities were confirmed by increasing blood GSH level.
4. When comparing all three drugs alone: pioglitazone revealed the most potent drug of the three in treating arthritic rats. The second place was occupied by both caffeic acid methyl ester and pentoxifylline with nearly equivalent potency in treating arthritic rats.
5. This study demonstrated that Pg alone has promising role in treatment of RA. However, it was more active in combination with MTX than each alone.
6. The present investigations also suggested that these drugs combinations with MTX can play a promising role in treatment of RA. But when comparing the three combinations; th combination of pioglitazone with methotrexate showed the most potent one. The second combination was caffeic acid methyl ester with methotrexate. Finally, become the least potent one, was the combination of pentoxifylline with methotrexate.
7. Over and above, when comparison between the combinations and each drug alone was held, it revealed that; all combinations showed more efficacy and potency than each dug alone.
Recommendations
Caffeic acid methyl ester, pentoxifylline and pioglitazone may have a future promising role in the treatment of RA either alone or in combination with methotrexate. However, our study doesn’t conclude final use of these drugs for treatment of RA, and need further researches and clinical trials.