الفهرس 
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Abstract
In The Current Study, The Possible Beneficial Effects Of Paroxetine, Rivastigmine And Perindopril Were Studied In Comparison With Dexamethasone As Standard Drug For Treatment Of CFA-Induced Rheumatoid Arthritis (RA) In Rats.
For Induction Of RA, Rats Were Injected With Three Subcutaneous Doses Of CFA, Each Of 0.4 Ml, In Three Different Limbs On Days 1, 4 And 7. The Tested Drugs Were Administered For Thirteen Consecutive Days, Starting from 13th To 26th Day After CFA Administration .
The Anti-Rheumatoid Effects Of The Test Drugs Were Estimated On Serum RF, MMP-3, COMP, IL-6, TNF-Α And MCP-1levels. Furthermore, The Effect Of Test Drugs Was Studied On Serum Levels Of MDA And Reduced GSH As Oxidative Stress Biomarkers. In Addition, Histopathological Examination Was Done To Support The Estimated Biomarkers. Finally, Immunohistochemical Analysis Of Caspase-3 Expression Level Along With Determination Of RANKL And OPG Expression Levels Were Performed Using Q RT-PCR As A Possible Molecular Mechanisms For The Anti-Rheumatoid Effects Of The Test Drugs.
The Main Findings Of The Present Study Can Be Summarized As Follows:
1- CFA Significantly Increased Serum RF, MMP-3 And COMP As Compared To Normal Control Group.
2- Dexamethasone, Paroxetine, Rivastigmine And Perindopril Significantly Decreased Serum RF, MMP-3 And COMP As Compared To RA Control Group.
3- CFA Significantly Increased Serum IL-6 And TNF-Α As Compared To Normal Control Group.
4- Dexamethasone, Paroxetine, Rivastigmine And Perindopril Significantly Decreased Serum IL-6 And TNF- Α As Compared To RA Control Group.
5- CFA Significantly Increased Serum MCP-1 As Compared To Normal Control Group.
6- Dexamethasone, Paroxetine, Rivastigmine And Perindopril Significantly Decreased Serum MCP-1 As Compared To RA Control Group.
7- CFA Significantly Increased Serum MDA And Decreased Serum GSH As Compared To Normal Control Group.
8- Dexamethasone, Paroxetine, Rivastigmine And Perindopril Significantly Decreased Serum MDA And Increased Serum GSH As Compared To RA Control Group.
9- CFA Significantly Increased Tissue RANKL And Decreased Tissue OPG Which In Turn Resulted In Significant Increase In RANKL/OPG Ratio As Compared To Normal Control Group.
10- Dexamethasone, Paroxetine, Rivastigmine And Perindopril Significantly Decreased Tissue RANKL And Increased Tissue OPG Causing A Significant Decrease In RANKL/OPG Ratio As Compared To RA Control Group.
11- CFA Significantly Increased Caspase-3 Protein Expression Level In The Joint Tissue As Compared To Normal Control Group.
12- Dexamethasone, Paroxetine, Rivastigmine And Perindopril Significantly Decreased Caspase-3 Protein Expression Level As Compared To RA Control Group.
13- CFA Produced Severe Histopathological Changes As Reflected By The Proliferation Of Synovial Membrane, Pannus Formation, Inflammatory Exudate In The Joint Space And Focal Necrosis Of The Cartilage.
14- Dexamethasone, Paroxetine, Rivastigmine And Perindopril Showed Significant Improvement Of Joint Damage As Revealed By Return Of Synovial Fluid Into The Articular Space, Less Pannus Formation And Less Synovial Proliferation As Compared To RA Group.
Depending On The Previous Findings, It Can Be Concluded That:
1- Complete Freund’s Adjuvant Induces RA Through Stimulation Of Inflammatory Pathways, Oxidative Stress, Apoptosis As Well As Increasing RANKL/OPG Ratio Causing Joint Damage.
2- The Tested Drugs Used Including Paroxetine, Rivastigmine And Perindopril May Offer Promising Lines For Treatment Of RA. The Effects Obtained By The Tested Drugs Were Comparable To That Obtained By Dexamethasone.
3- The Most Likely Proposed Mechanisms For The Anti-Rheumatic Effects Conferred By These Drugs Is Strongly Related To Their Antioxidant, Anti-Inflammatory, Anti-Apoptotic Properties Along With Modulation Of The RANKL/OPG Expression Levels
Further Clinical Studies Are Required To Elucidate The Feasibility Of Application Of Such Drug Classes Clinically In The Management Of Rheumatoid Arthritis.