الفهرس 
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Abstract
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with an unknown cause that induces joint swelling, discomfort, in addition to bone and cartilage degeneration, resulting in functional impairment and poor quality of life.
The prevalence of RA ranges from 1% to 2% of the general population worldwide. It affects three times as many women as it does males, and it commonly appears in the fourth and fifth decades of life. CFA-induced arthritis is a chronic polyarthritis paradigm that, in many ways, resembles human RA. It is one of the best experimental models for detecting and evaluating drugs having anti-inflammatory or anti-rheumatic properties activity.
The most common treatments for RA include non-steroidal anti-inflammatory medications (NSAIDs), steroidal medicines, and immunosuppressants. However, these medications are known to cause a variety of adverse effects, including gastrointestinal diseases, immunodeficiency, and humoral abnormalities. Natural products have been used successfully for centuries with no apparent toxicity or negative effects.
The present study has been conducted to elucidate the therapeutic
effect of curcumin, MSCs and their combination against complete
Freund’s adjuvant (CFA) induced arthritis in experimental rats.
Experimental animals were organized into 16 groups including 6 animals per each.
Eight groups including male rats and the other eight groups including females rats as following:
group 1 (G1): Normal control group that received water.
group 2 (G2): Carboxymethyl cellulose (CMC) control group. Rats were received 1% CMC (5ml/ kg b.wt. /day) through gastric intubation daily.
group 3 (G3): Curcumin control group. Rats were orally administrated curcumin. Curcumin is dissolved in 1 % CMC (Carboxymethyl cellulose) at 1 % concentration and was administrated orally (100 mg /kg b.wt. /day) (Hemeida and Mohafez, 2008)
group 4 (G4): Mesenchymal stem cells (MSCs) control group. Rats were received injection of MSCs in tail vein (phosphate buffer saline containing 1 x 106 in each injection and single) injection each week).
Groups 5 (G5): Arthritic group. Rats were subcutaneously injected with CFA (0.1mg/kg b. wt. single dose) into a foot pad of the right hind leg (Whitehouse 2007).
group 6 (G6): Arthritic group treated with curcumin. Rats were injected with CFA like in G5 and orally administrated curcumin like in G4.
group 7 (G7): Arthritic group treated with MSCs. Rats were injected with CFA like in G5 in parallel to injection of MSCs in tail vein like in G2.
group 8 (G8): Arthritic group treated with both MSCs and curcumin. Rats were injected with CFA (as in G5) in parallel to injection of MSCs in tail vein like in G2 and orally administration of curcumin like in G4.
At the end of experiment, the right hind paw circumference, right
hind paw volume and thickness were measured. Rats were sacrificed under
mild diethyl ether anesthesia and blood samples were collected from
jugular vein. After decapitation and dissection, tissue samples (testis, ovary
spleen, thymus and ankle joint) were rapidly excised for physiological and
biochemical assays as well as for histopathological studies. CFA-induced
arthritis group (arthritic control) was compared to the normal one, while
the arthritic rats treated with curcumin and MSCs were compared with the arthritic control group.
Results showed that CFA-administration caused a marked rise in
paw edema of the arthritic rats as indicated by increase in right hind paw
circumference, right hind paw volume and thickness but treatment with
both curcumin and MSCs 21 days showed marked ameliorated decrease for those parameters compared with normal control one which suggest the effectiveness of these treatments on RA.
Considering oxidative stress and antioxidant defense system, the LPO content was significantly increased in CFA-administered rats while the GSH content and the activities of antioxidant enzymes SOD, GPx and GST were significantly decreased.
The treatment with curcumin and MSCs markedly decreased the elevated LPO contents. On the other hand, the decreased GSH content and GPx, GST and SOD activities were ameliorated successfully by curcumin and MSCs. These results refer that both curcumin and MSCs play an important role in preventing and treating the CFA-induced arthritis through inhibition of the oxidative stress and enhancement of antioxidant defense system after 21 days. Serum RF, inflammatory (PGE2, TNF-α and IL- 17) significantly increase in arthritic control rats. On the other hand, serum anti-inflammatory (IL-10 and IL-13) cytokines levels revealed significant decrease in CFA induced arthritic rats while treatments with curcumin and MSCs showed marked alleviation for these inflammatory and anti-inflammatory cytokines after 21 days. The mRNA expression of COX-1 and IL-6 gene levels of spleen showed significant increase in CFA induced arthritis while the anti-inflammatory cytokine IL-4 mRNA gene expression revealed significant decrease in arthritic rats. Significant histopathological alterations in joints, spleen, thymus, ovary and testis were also observed in the CFA-administered animals. Curcumin and MSCs seemed to exhibit anti-rheumatic activity against CFA- administered male and female albino rats due to their antioxidant properties and their ability to enhance lipid peroxidation content.
Regarding histopathology, the former results of the immunological
indices are supported by the histopathological examination of the ankle
joint sections. The curcumin and MSCs treatment showed an obvious reduction in degeneration of cartilage, inflammatory cells infiltration and pannus formation, mitotic figure appearance and disappearance of lymphoblasts activation and congested blood capillaries and mitotic figure appearance in thymus when compared with the arthritic control group.
In conclusion, acombination of curcumin and MSCs have potent anti-inflammatory effects against CFA-induced arthritic rats which manifested by activation of Th2 cells and attenuation of Th1 and Th17 cytokines production. Also curcumin and MSCs have the ability to suppress oxidative stress and enhanced the antioxidant defense system in CFA-induced arthritic rats.
Thus, these treatments may have potential effects in the prevention and
therapy of the rheumatoid arthritis which may be mediated via their modulatory effects on Th1/Th2/Th17 cytokines and their antioxidant activities.
Curcumin and MSCs together successfully inhibited the degenerative development of CFA-induced arthritis in this study and had potential anti-arthritic and anti-inflammatory efficacies in CFA-induced arthritic male and female rats than their use singly.