Untitled

Abstract

Five experimental models were developed in different groups of Wistar rats (N = 15) to study selective COX-2-inhibitor NSAIDs such as celecoxib and rofecoxib, as follows: (1) dose-dependent oral Celecoxib and Rofecoxib for 5 days, and 24 hr after oral indomethacin; (2) Same as 1 but subcutaneously; (3) gastric ulcer induced by glacial acetic acid; (4) duodenal ulcer induced by cysteamine; and (5) stress by immobilization and immersion in water at 15 degrees C for 6 hr. Celecoxib and Rofecoxib, either orally or subcutaneously, did not produce necrotic lesions in healthy gastrointestinal mucosa (0%), showing normal histology. In contrast, previously indomethacin-induced lesions were aggravated (90%, P < 0.001). Total necrosis in the small intestine as well as increased ulcers and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also aggravation of the necrotic gastric area in stress (60-90%, P < 0.05). Celecoxib and rofecoxib showed neutrophilia (5000/mm3) similar to that with indomethacin. In contrast, there was no leukocyte infiltration in the gastric múcosa; thus, we can consider it a selective COX-2 NSAID. In conclusion, celecoxib and rofecoxib at doses causing COX-2 but not COX-1 inhibition did not produce toxic lesions in healthy gastrointestinal mucosa, yielding a broad therapeutic margin. In contrast, when administered in altered gastrointestinal mucosa, they aggravated and complicated gastric ulcers as well as necrosis in the small intestine, consequently restricting their clinical use.

Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors

“…given to four animals to obtain the corresponding doseresponse. The doses were chosen in the therapeutic range from preliminary pharmacokinetic data, eicosanoid profiles, and current literature (20)(21)(22)(23). For instance, celecoxib was administered at higher doses because it has a larger volume of distribution and is less efficacious when compared with rofecoxib.…”

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

“…Slomiany's group 54) found that platelet-activating factor (PAF) inhibitor, BN52020, significantly delayed the healing of acetic acid ulcers in rats, possibly due to decreased COX-2 protein expression, an increased rate of epithelial cell apoptosis, and increases in TNFa and mucosal NOS-2 activity. Laudanno et al 55) reported that both celecoxib and rofecoxib significantly aggravated and complicated gastric ulcers induced by acetic acid methods.…”

Severe Bone Marrow Suppression Accompanying Pulmonary Infection and Hemorrhage of the Digestive Tract Associated with Leflunomide and Low-dose Methotrexate Combination Therapy

“…[56] Third, discontinuation of MTX and LEF combination therapy and the use of symptomatic treatment resulted in marked improvement of our patient's condition, suggesting that a drug-related adverse reaction had occurred. Fourth, although other concomitant agents, such as celecoxib, can cause gastrointestinal damage and increase bleeding risk,[9] hematologic toxicity associated with celecoxib has not been reported thus far. However, methylprednisolone can stimulate the hematopoietic function of bone marrow, increasing the number of circulating neutrophils and platelets as well as inducing erythropoiesis; moreover, as the actions of several other agents included in adjuvant therapy are mild without side effects of this type, the contribution of other concomitant agents can be excluded.…”