الفهرس 
- OsteoarthritisOnly 14 pages are availabe for public view
 |  | from | 135 |  |  |
| | | from | 135 | | |
Abstract
Osteoarthritis has the highest prevalence of all forms of arthritis in the world
and is the leading cause of disability due to pain. It is a debilitating disease which is
associated with a large societal and economic burden, in addition to the physical and
psychological sequelae.
Osteoarthritis is a complex progressive disease process where the subchondral
bone and cartilage act as mechanical dampers as well as sources for inflammatory
mediators. OA pathophysiology nowadays is further considered an inflammatory
condition rather than just being a ”wear and tear” theory.
High levels of pro-inflammatory cytokines have been found in the cartilage as
well as in synovial fluid from OA patients and several experimental animal models of
OA. Among these cytokines, LTs, TNF-alpha, IL-1B and IL-6 in the synovial tissue
and are considered as effector mediators in the OA pathogenesis. The increased
production of these cytokines induces catabolic events as they downregulate the
synthesis of ECM structural components, including proteoglycan by enhancing MMPs
resulting in bone and cartilage remodeling and progression of OA.
MIA - a cellular glycolytic inhibitor - was used in the present study for
induction of OA because of its mechanism ”which is composed of successive
progressive steps” in inducing OA. It inhibits glyceraldehyde-3-phosphate
dehydrogenase of the Krebs cycle leading to the death of chondrocytes. This in turn
causes osteophyte formation and articular cartilage degradation as lesioning of the
articular cartilage is observed and there is a marked depletion of proteoglycans. The
result is rapid inflammation and pain.
Curative therapeutics are unavailable for OA. The main goals of current OA
pharmacologic therapy are the control of pain and improvement of joint function.
Moreover, chronic intake of these drugs may result in severe adverse effects.
Commonly prescribed OA medications include NSAIDs, analgesic drugs, locally
administered corticosteroids. For many patients, the lack of disease modifying OA
drugs results in progressive cartilage damage that eventually necessitates surgical
intervention. The novel idea here is that until now, almost all the available oral therapy are symptomatic, most of suggested disease modifying drugs are injectables.
This study hypothesized that zafirlukast, being a leukotriene receptor
antagonist (LTRA) can be a considerable pharmacotherapy for treatment of early OA
that can interfere with the disease progression and decrease pathological changes.
Leukotriens are involved in the inflammatory process that leads to catabolic events
as they downregulate the synthesis of ECM structural components, including
proteoglycan by enhancing MMPs resulting in remodeling of bone and cartilage and
progression of OA.