Effects of Celecoxib on Acid-Challenged Gastric Mucosa of Rats: Comparison with Metamizol and Piroxicam

Abstract

Selective COX-2 inhibitors have been shown to produce fewer gastrointestinal adverse reactions than classical NSAIDs. Nevertheless, these new agents may worsen and delay the healing of experimentally induced gastric ulcers in animals. In this study, we compared the effects of a selective COX-2 inhibitor (celecoxib), a preferential COX-1 inhibitor (piroxicam), and a nonnarcotic analgesic (metamizol) on normal gastric mucosa of rats and, on the other hand, in a setting of preexisting acute gastric lesions induced by 0.6 N hydrochloric acid. Under normal conditions, only piroxicam produced appreciable gastric lesions. However, after acid challenge the three assayed drugs induced significant macroscopic and microscopic damage. Myeloperoxidase activity as an index of neutrophil infiltration was elevated with celecoxib and piroxicam on normal gastric mucosa. On inflamed mucosa, celecoxib augmented enzymatic activity at the lower dose, which was parallelled by an increase in the interleukin 1beta level. Acid instillaton produced a significant rise in PGE2 content at 7 hr. Drug treatment after acid challenge decreased prostaglandin values in all cases, although to a lesser extent than after single drug dose administration. COX-2 mRNA expression was visible 1 hr after acid application, whereas COX-2 protein could only be detected at 7 hr. Piroxicam increased both expression levels. All NSAIDs enhanced transforming growth factor alpha and epidermal growth factor receptor immunoreactivity around the acid-induced lesions. It is concluded that selective COX-2 inhibitors, like conventional NSAIDs, impair the healing of gastric damage, and therefore special attention should be paid in patients with gastric pathologies.

Antinociceptive action of 4-methyl-5-trifluoromethyl-5-hydroxy-4, 5-dihydro-1H-pyrazole methyl ester in models of inflammatory pain in mice

“…In fact, in contrast with traditional NSAIDs, dipyrone did not cause apparent gastrointestinal lesions in subchronic treatment in rats (Sanchez et al, 2002;Bereguer et al, 2004). In this study, the traditional NSAID indomethacin caused gastric mucosal damage.…”

Nonsteroidal anti-inflammatory drugs in cats: a review

“…Work in rodents using acid or chemically‐induced gastric ulceration has shown that selective COX‐2 inhibitors can delay or prevent healing of the ulcers (Mizuno et al. 1997; Berenguer et al. 2004), and analysis of COX‐2 expression and localization indicated that COX‐2 expression was upregulated during injury and was localized to reparative epithelium at the periphery of the wound.…”

The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives

“…Indeed, while indomethacin comparably inhibited carrageenan‐evoked hyperalgesia/oedema, dipyrone was an effective antihyperalgesic and a poor anti‐inflammatory agent (Lorenzetti and Ferreira, ). Dipyrone failed to reduce PG levels in rat tissues and, accordingly, dipyrone gastrointestinal toxicity is negligible (Weithmann and Alpermann, ; Brogden, ; Sanchez et al ., ; Berenguer et al ., ). Thus, the pharmacological actions of PDs do not replicate the COX‐dependent effects of NSAIDs/coxibs and additional mechanisms (Lorenzetti and Ferreira, ; Sachs et al ., ) have not received further support.…”