الفهرس 
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Abstract
OA is major cause of chronic invalidity worldwide and there is an increasing need to prevent or slow the progression of the disease. Oxidative stress and inflammation are the main destructive pathways in OA leading to damage of cartilage. A lot of research is being invested in finding cell/biomaterial based implants that have both the required physical properties to support cartilage function and anti-inflammatory properties to support the healing process of the damaged cartilage. Alginate is a biocompatible, FDA approved, and widely available polysaccharide, that has found numerous clinical applications, as it is considered inert.
In this context, our study designed to investigate the effect of alginate extracted from brown algae on osteoarthritis in rats inducted by mono sodium iodo-acetate. The present work was done on 77 rats divided into group I: 28 male rats, control group. group II: inducted group with monoiodoacetate (MIA) (28 male rats). group III .21 male rats treated of inducted group with alginate.
Histopathological and biochemical results of group I revealed that Intra-articular injection of MIA by 2 weeks, induced joints arthritis which had a mild focal fissuring in the upper third, disorganization of chondrocytes and focal chondroid hyperplasia and Neovascularization of the matrix. Associated by a significant increase in IL-1β, TNF-α, aggrecanase, β-glucuronidase, MDA and significant decrease in the level of glutathione when compared with that of the control. The biochemical results of the present study showed significant increase in lipid Peroxidation product MDA & significant decrease in non-enzymatic antioxidant marker reduced glutathione. Where, MDA levels were found to be significantly increased in osteoarthritis rats than in healthy rats, indicating an increase in the process of lipid Peroxidation in osteoarthritic
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animals. Reduced glutathione levels were found to be significantly decreased in rats with osteoarthritis than in healthy rats indicating inadequate antioxidant mechanism in rats suffering from osteoarthritis. Presumed that oxidative stress involved in pathogenesis of OA which results due to increased free radical production. This leads to alteration in the antioxidant status which varies with the individual antioxidant depending upon their biochemical action.
The present immunological results demonstrated that the intra-articular injection of alginate to the osteoarthritic rats produced significant decreases in the levels of IL-1β and TNF-α at two weeks from treatment when compared with that of two weeks inducted rats. Meanwhile, the decreases were more pronounced at 4 and 8 weeks from the intra-articular injection with alginate.
On the same manner, the biochemical results showed significant increase in lipid Peroxidation product MDA & significant decrease in non-enzymatic antioxidant marker reduced glutathione in osteoarthritic animals. Therefore, Oxidative stress and inflammation are the main destructive pathways in OA leading to damage of cartilage. Meanwhile, the alginate treatment attenuate the MIA induced oxidative stress which manifested by high significant decrease in the level of MDA concomitant with significant increase in the level of GSH in the blood of treated inducted rats at 2, 4 and 8 weeks from intra-articular alginate injection when compared with that of MIA inducted rats.
Histopathological examination were in consistent and confirm the biochemical data obtained in the present study which evident that the alginates possess anti-inflammatory effect which manifested by the high significant decreases in the levels of IL1-β and TNF-α which consequently induced high significant decreases in the enzymatic activities level of β-glucuronidase and aggrecanase . Moreover, alginate has
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antioxidant effect which was evident by high significant decrease in the levels of MDA concomitant with striking significant increase in the level of GSH. . Alginate treatment significantly reduced the activity of lysosomal enzymes that indicates the reduction of connective tissue degradation. Furthermore, it may be suggested that alginate ameliorate the lesions happened in osteoarthritic knees as observed clear by herein histopathological investigation.
However, the correlation coefficient between different parameters revealed that, there was a significant negative correlation between different parameters and GSH. Also, Pearson correlation between MDA and the remain studied parameters indicated highly significant positive correlation. Meanwhile, high significant positive correlation observed between β-glucouronidase and Aggreacanase, IL1β and TNF-α. On the same time there is a significant positive correlation between IL1β and TNF-α.
In conclusion, the present study revealed that alginate isolated from cystoseira exhibits significant anti-inflammatory and Anti-osteoarthritic potential against MIA induced osteoarthritic rats this is due to, its immunological protection, antagonistic action against proinflammatory cytokines and lysosomal membrane stabilization during arthritis as well as their antioxidant activity.