الفهرس 
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Abstract
Osteoarthritis (OA) is one of the most common joint disorders worldwide. Treatment options remain largely limited to painkillers and anti-inflammatory drugs, which only provide symptomatic relief. However, with better understanding OA pathogenesis, meticulous attention was paid to develop drugs that can affect the underlying joint pathological changes, slowdown their progress or even reverse them and eventually decrease the need for joint replacement. This group of drugs is referred to as DMOADs e.g glucosamine sulfate and diacerein. Until now there is no an ideal drug used for improvement of OA underlying pathological changes, so there is continuous research to find an effective drug that can improve the joint function and structure. Statins widely used in the cardiovascular medicine, are emerging as a potential pharmacologic agent for treatment of OA. Statins widely used in the cardiovascular medicine, are emerging as a potential pharmacologic agent for treatment of OA. Statins effect on OA are assumed to be due to both cholesterol lowering effect and their pleotropic effects including anti-inflammatory, anticatabolic, antioxidant that help in modification of the underlying OA pathological changes.The aim of the work: To study the effect of atorvastatin in comparison with glucosamine sulfate and diacerein in an experimental model of osteoarthritis. Also, to assess and compare the anti-inflammatory and analgesic effects of these three tested drugs in an experimental model of inflammation. Materials andMethods:Forty adult male Sprague-Dawley rats (250-300gms) were haphazardly separated into five groups of eight rats each: control normal group, surgically induced osteoarthritic non treated group, glucosamine treated OA group, diacerein treated OA group and atorvastatin treated OA group. Drugs were administrated on the first day of surgery once every day for 42 days. Maximum angle of knee extension were measured,histopathological examination of knee joints was done in all groups using hematoxylin and eosin stain. Serum Interleukin-1beta (IL-1β), Matrix metalloprotinase13 (MMP13), reduced glutathione (GSH) concentration were biochemically assessed in all groups.To evaluate the antiinfalamatory and analgesic effects of the tested drugs,induction of paw edema was done by sub-plantar injection of all animals by 0.1 ml of 1% carrageenan dissolved in saline except the control normal group. The animals were pretreated with the drugs 1h before carrageenan injection. Thirty six Sprague-Dawley male rats (weighing 250-300) were used and were divided into six equal groups (six rats each) as follows:control normal group, carrageenan treated group, indomethacin pretreated group, glucosamine pretreated group, diacerein pretreated group and atorvastatin treated OA group. The paw thickness was recorded using dial gauge caliper and also nociceptive threshold was recorded using an analgesiometer at 1, 2, 3, 4 h and 24h after carrageenan injection and compared to the control normal group. Results:Atorvastatin showed a significant improvement of all parameters more than that glucosamine. As comparing with diacerein, atorvastatin showed a more significant improvement of histopathological score, a more significant reduction in the increased MMP13, however less significant than diacerein in the reduction of IL1-β and no significant difference with diacerein in improvement of maximum angle of knee extension. .As regard paw edema and hyperalgesia test, glucosamine, diacerein and atorvastatin showed a significant improvement of the increased paw thickness and the decreased nociceptive threshold at 1, 2, 3, 4, 24hour after carrageenan injection, but less than indomethacin. Diacerein achieved better results than glucosamine while atorvastatin has better results than either glucosamine or diacerein Conclusion:Based on these results, atorvastatin can ameliorate development of OA in meniscal tear model in rats. It can largely limit the underlying histopathological damage and the participating biochemical markers of OA including inflammatory, catabolic and oxidant markers, so the present study represents atorvastatin as potentially useful DMOAD especially for OA elderly patients group of age who usually may have hyperlipidemia and atherosclerosis