الفهرس 
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Abstract
Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of the articular cartilage, sclerosis of subchondral bone and osteophyte formation. The incidence of OAincreases during every decade of life and by the age of 65 years, almost one-third of the population develops OAof the knee joints. Degeneration of articular cartilage is accompanied by chronic pain and significant disability in OA. However, at present no treatment is available which prevents or cures OA. Various factors, including obesity, previous injury and lifestyle, have been related to the pathogenesis of OA. Current concepts of the pathogenic mechanisms of OAsuggest a shift in the homeostatic balance between the destruction and synthesis of bone and cartilage. Notably, previous studies have indi¬cated the involvement of oxidative stress in the pathogenesis and progression of OA.
Oxidative stress is the disturbance in the state of equi¬librium of pro-oxidant and anti-oxidant systems in cells and tissues. Reactive oxygen species (ROS) are highly reactive transient chemical substances, which include nitric oxide, superoxide anion, hydrogen peroxide and hydroxy radical, with the potential to initiate cellular damage by acting on molecules, such as proteins, lipids and nucleic acids. Furthermore, lipid peroxides, i.e., polyunsaturated fatty acids peroxidized by ROS, have also been shown to induce tissue injury.
Ozone readily dissolves in the water either of the plasma or into the extracellular fluids, or into the thin layer of water covering the skin. It being a potent oxidant, reacts immediately with a number of ions and biomolecules present in biological fluids, namely antioxidants, proteins, carbohydrates and preferentially polyunsaturated fatty acids (PUFAs) bound to albumin. Ozone is exhausted and only ROS (mostly hydrogen peroxide) and lipid ozonation product (LOPs) are responsible for the successive and multiple biochemical reactions happening in different cells all over the body.
Ozone therapy is a safety and therapeutic medication,Taking into account different biological effects of ozone therapy, such as: the stimulation of the anti-oxidant defense system counteracting the intracellular pro-oxidant status, improvement in the oxygen deliver to tissues and its anti-inflammatory effects.
This study was designed to showthe effect of treatment with medical ozone on the antioxidant status& inflammatory marker in Knee Osteoarthritic patients. Subjects were divided into two groups: group (I) were 15 subjects with no previous history of any osteoarthritis disease served as control group. Group (II) were 25 patients who had diagnosed with Knee Osteoarthritis by Plain X-rays according to the criteria of American College of Rheumatology (ACR) and were treated with both :-
1) Local Ozone (O3) injection in the form of :
a) 6 intra-articular injection of O3in concentration of 7-10 γ/10 ml.
b) 12 peri-articular injection of O3 in concentration of 5-7γ/10 ml.
2) Systemic O3 therapy through rectal insufflation, 12 rectal doses of 200 ml ozone in oxygen gas mixture in concentration varing from 10-35 γ/ml.
Both local and systemic were administrated twice weekly for 6 weeks.
Fasting blood samples (6 – 8 hours) were withdrawn from each subject of Group II before and at the end of ozone treatment (after 6 weeks) and a single blood sample was collected from Group Ifor assessment of C-Reactive Protein (CRP), Rheumatoid Factor(RF),erythrocyte sedimentation rate (ESR), lipid peroxidation, total antioxidant capacity by ferric reducing antioxidant power (FRAP), Nitric oxide end products (NOx), Total Glutathione (tGSH), reduced glutathione, glutathione disulfide (GSSG) and Interleukin-6 (IL-6).
The results indicated that,decrease in the levels of antioxidant such as FRAP, tGSH, rGSH,redox potential,increase of reactive oxygen species such as MDA,NO, and inflammatory marker as IL-6 of patients before ozone therapy compared to control.
Ozone therapy increases in the levels of antioxidant such as FRAP, tGSH, rGSH,redox potential,decrease of reactive oxygen species such as MDA, NO, and inflammatory marker as IL-6 of patient after treatment compared to patient before treatment.
Also ozone therapy diminished the oxidative stress, achieving an intra-articular redox balance, as well as a reduction of pain in patients. An increase in the quality of life of patients with knee osteoarthritis was observed.
The result showed a significantly increase in CRP, the 1sth ESRand the 2ndh ESR levels of patients before treatment compared to control,their levels after treatment were significantly decrease compared to their levels before treatment.
The results of the present study confirm the validation of save painkilling effect of ozone –oxygen injection on osteoarthritis joints. Due to its long term effect on pain relief, it seems some histological changes are involved in its mechanism of action. The antioxidant mechanism, which become activated after ozone- oxygen injection possibly reverses the degeneration processes in the joints and their surrounding tissues.
from the results of this study and other related studies it can be concluded that:
1. Oxidative stress is associated with the development of OAas there was increase in oxidative stress (MDA and NO), decrease in total antioxidant measured by FRAP and non-enzymatic antioxidant as GSH alsodecrease redox potential, andincrease serum IL-6 level compared to control.
2. Combined ozone therapy (Local injection in the form of intra-articular and peri-articular injection and systemic through rectal insufflation) diminished the oxidative stress, achieving an intra-articular redox balance, as well as a significant reduction of pain.
3. Ozone therapy decrease oxidative stress (MDA and NO), increase in total antioxidant measured by FRAP and non-enzymatic antioxidant as GSH and increase redox potential compared to their level before treatment.
4. Ozone therapy has a possible benefit in attenuating the inflammatory responseas evidenced by the decrease inserum IL-6 level.