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

Weichman, Barry M.; Chau, T. T.; Róna, G

doi:10.1002/art.1780300419

Cited by 19 publications

(8 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The anti-arthritic activity of etodolac has been shown in animal models of experimentally-induced arthritis, such as adjuvant arthritis in rats, and type II collagen arthritis in mice [3][4][5]. These reports also showed that etodolac inhibits the development of bone destruction in experimentally-induced arthritis.…”

Section: Introductionmentioning

confidence: 85%

Effect of etodolac, a new nonsteroidal anti-inflammatory drug, in MRL/lpr mice with articular lesions

et al. 1991

View full text Add to dashboard Cite

Etodolac, a new nonsteroidal anti-inflammatory drug, was administered orally at doses of 1 and 5 mg/kg to MRL/MpJ-lpr/lpr (MRL/lpr) mice, and its effect on articular lesions was compared with that of indomethacin. Both etodolac and indomethacin significantly reduced swelling of the hind paw. Histopathological examination showed that etodolac significantly reduced cartilage and bone damage, whereas indomethacin treatment did not achieve a statistically significant effect. Rheumatoid factors were not affected by either etodolac or indomethacin. These results indicate that etodolac delays the development of arthritis in MRL/lpr mice, and reduces cartilage and bone damage.

show abstract

Section: Introductionmentioning

confidence: 85%

Effect of etodolac, a new nonsteroidal anti-inflammatory drug, in MRL/lpr mice with articular lesions

et al. 1991

View full text Add to dashboard Cite

show abstract

“…Accumulated evidence has also shown the bonesparing effects of COX-2 inhibitors using mouse and rat models in vitro and in vivo. (10,34,(44)(45)(46)(47) Because both COX-2 and CAII show 80-90% homologies in nucleotides and amino acids among mice, rats, and humans, (48)(49)(50) these results may be applicable to humans. For the clinical application of COX-2 selective agents as a treatment of bone resorptive disorders including RA, however, we should be cautious not only with cardiovascular events above, but also with possible inhibition of bone repair and ingrowth that has recently been reported in animal models when administered for a long period of time.…”

Section: Figmentioning

confidence: 99%

Suppression of Adjuvant-Induced Arthritic Bone Destruction by Cyclooxygenase-2 Selective Agents With and Without Inhibitory Potency Against Carbonic Anhydrase II

Katagiri

Ogasawara

Hoshi

et al. 2006

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

In vitro assays revealed that COX-2 inhibitors with CA II inhibitory potency suppressed both differentiation and activity of osteoclasts, whereas that without the potency reduced only osteoclast differentiation. However, all COX-2 inhibitors similarly suppressed bone destruction in adjuvant-induced arthritic rats, indicating that suppression of osteoclast differentiation is more effective than that of osteoclast activity for the treatment.Introduction: Cyclooxygenase (COX)-2 and carbonic anhydrase II (CA II) are known to play important roles in the differentiation of osteoclasts and the activity of mature osteoclasts, respectively. Because several COX-2 selective agents were recently found to possess an inhibitory potency against CA II, this study compared the bone sparing effects of COX-2 selective agents with and without the CA II inhibitory potency. Materials and Methods: Osteoclast differentiation was determined by the mouse co-culture system of osteoblasts and bone marrow cells, and mature osteoclast activity was measured by the pit area on a dentine slice resorbed by osteoclasts generated and isolated from bone marrow cells. In vivo effects on arthritic bone destruction were determined by radiological and histological analyses of hind-paws of adjuvant-induced arthritic (AIA) rats. Results: CA II was expressed predominantly in mature osteoclasts, but not in the precursors. CA II activity was inhibited by sulfonamide-type COX-2 selective agents celecoxib and JTE-522 similarly to a CA II inhibitor acetazolamide, but not by a methylsulfone-type COX-2 inhibitor rofecoxib. In vitro assays clearly revealed that celecoxib and JTE-522 suppressed both differentiation and activity of osteoclasts, whereas rofecoxib and acetazolamide suppressed only osteoclast differentiation and activation, respectively. However, bone destruction in AIA rats was potently and similarly suppressed by all COX-2 selective agents whether with or without CA II inhibitory potency, although only moderately by acetazolamide. Conclusions: Suppression of osteoclast differentiation by COX-2 inhibition is more effective than suppression of mature osteoclast activity by CA II inhibition for the treatment of arthritic bone destruction.

show abstract

“…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].…”

Section: Discussionmentioning

confidence: 99%

“…Rats were injected with Freund's complete adjuvant (0.05 ml of a fine suspension of 5 mg killed and dried Mycobacterium butyricum suspended in 1 ml mineral oil, Difco Laboratories, Detroit MI) in the foot pad of one hind limb on day 0 [11]. On day 14, rats with an injected paw volume increase of at least 0.5 ml between days 10 and 14, and only animals with a total injected paw volume of 4-7 ml were selected for further experimentation.…”

Section: Adjuvant Arthritic Ratsmentioning

confidence: 99%

“…Additionally, the inflammatory mediator interleukin-I (IL-I) has been demonstrated to stimulate PGE 2 biosynthesis in bone cells [5], although IL-1 apparently does not require PGE 2 biosynthesis in order to stimulate bone resorption [6,7]. Lesions of experimental models of arthritic disease, such as adjuvant arthritis in rats, may be ameliorated by the administration of drugs which inhibit prostaglandin accumulation [8][9][10][11]. Although the adjuvant model has stimulated considerable debate regarding its suitability as a model of rheumatoid arthritis, it is a model in which bone and cartilage catabolic changes are well correlated with local inflammation [12,13].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Hayward

Howard²,

Neuman

et al. 1989

Agents and Actions

View full text Add to dashboard Cite

To investigate the role of PGE2 in the development of bone and joint pathology in rat adjuvant arthritis, hindlimb paws were evaluated by calcified tissue histologic techniques focusing on histochemical visualization of cartilage and bone lesions. Case studies of hindlimbs from normal, adjuvant arthritic, and etodolac-treated arthritic rats demonstrated the association of disease severity with inflammation, chondromalacia, replacement of adipose bone marrow with a fibroid marrow, osteoclastic bone resorption, synovial cysts, and pannus formation within the joints. Extensive periosteal intramembranous bone formation was temporally associated with joint destruction and medullary tissue pathology. In vivo data were correlated with in vitro effects of inflammatory mediators (IL-1, PGE2) on bone resorption. Etodolac blocked bone explant PGE2 accumulation at concentrations of 10(-7) M and higher, and inhibited bone resorption at concentrations of 10(-5) M and higher. The data indicate that in vitro and in vivo models of bone metabolism are well correlated regarding prostaglandin synthesis; that the inflammatory mediator PGE2 is largely responsible for the involvement of skeletal tissue in the adjuvant arthritis model; and that the effects of etodolac are specifically mediated by its ability to inhibit PGE2 accumulation in vivo.

show abstract

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

Cited by 19 publications

References 7 publications

Effect of etodolac, a new nonsteroidal anti-inflammatory drug, in MRL/lpr mice with articular lesions

Effect of etodolac, a new nonsteroidal anti-inflammatory drug, in MRL/lpr mice with articular lesions

Suppression of Adjuvant-Induced Arthritic Bone Destruction by Cyclooxygenase-2 Selective Agents With and Without Inhibitory Potency Against Carbonic Anhydrase II

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

Contact Info

Product

Resources

About