Effect of etodolac on articular and bone pathology associated with adjuvant arthritis in rats: A comparison with aspirin and naproxen

Abstract

The effect of treatment with the new anti-inflammatory drug etodolac on the articular and bone pathology associated with adjuvant arthritis in rats has been compared to the effects produced by aspirin and naproxen. Five measures of drug effect were made (changes in hind paw edema, body weight, normal hind leg function and articular damage as assessed by radiologic and histopathologic techniques). Drug treatment was initiated 16 days after adjuvant injection when arthritis was already established and continued for either 14 or 28 days. Etodolac produced a dose-related inhibition of all arthritic changes. Results from the radiologic study indicated that etodolac not only prevented the further development of articular damage by arthritis but actually caused a regression of these lesions established before drug treatment began. Similar results were obtained from the histopathologic study. Naproxen prevented the further development of arthritic damage but aspirin, although it decreased hind paw edema and increased body weight gains, had no significant effect on the articular damage produced by arthritis.

Prostaglandins in inflammatory bone pathology: Mechanism and therapeutic benefit of etodolac

“…2, 3). The accumulation of periosteal bone is in accord with previously reported disease dependent radiologic lucidity and amelioration by etodolac [10], as well as the report that PGE 2 directly stimulates the formation of new bone at newly formed foci [28]. Adjuvant injection has been previously associated with endosteal bone formation in rats [29], suggesting that bone and bone marrow involvement is a consequence of prostaglandin biosynthesis in this model.…”

“…The non-injected contralateral paw specimens in this study correspond to those paws from previous studies in which etodolac therapy was continued for 28 days [10]. While these observations confirm the pathology previously reported, they also provide histochemical data which are not readily available using decalcified tissue procedures, notably chondromalacia and changes in the mineralized tissues.…”

“…The histopathologic aspects of this study were initiated to directly evaluate calcified tissue involvement with disease progression, and not to repeat work previously described using standard decalcified tissue/paraffin embedding techniques [8,10,11]. The non-injected contralateral paw specimens in this study correspond to those paws from previous studies in which etodolac therapy was continued for 28 days [10].…”

The effect of etodolac on type II collagen-induced arthritis in mice

“…CIA is an autoimmune disease, since the immunization of mice with heterologous type II collagen gives rise to an arthritogenic reaction against autologous collagen [2]. Etodolac has been shown to have antiinflammatory and antiarthritic properties in the rat adjuvant arthritis (AA) model [3,4]. In the present study, CIA was used to test the action ofetodolac.…”

Histopathologic evaluation of the effects of etodolac in established adjuvant arthritis in rats: evidence for reversal of joint damage

“…In rats with established arthritis, etodolac reversed the bone and articular disease manifestations in the hindpaws, as assessed by either radiologic or histopathologic criteria, whereas naproxen and ibuprofen only inhibited the progression of the disease, and aspirin was unable to alter the course of the arthritis (7,8). In those studies, drug administration was instituted on day 16 after adjuvant, when soft tissue changes were scored at maximum severity, but bone and articular changes were considered mild to moderate by histopathologic assessment.…”