Gastric Damage Induced by Subchronic Administration of Preferential Cyclooxygenase-1 and Cyclooxygenase-2 Inhibitors in Rats

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known to induce gastrointestinal damage including bleeding, ulceration and perforation in humans and animals. The aim of this study was to compare the effects of two oxicams, preferential cyclooxygenase (COX)-1 or COX-2 inhibitors, on both gastric mucosa and some biological parameters (hematological, hepatic and renal) after subchronic administration (14 and 28 days) in rats. Neutrophil infiltration was also assessed. Equipotent doses of meloxicam (3.75 and 7.5 mg/kg) and piroxicam (5 and 10 mg/kg) were administered. Both drugs dose-dependently caused multiple gastric erosions and hemorrhage in rats after 14 and 28 days of administration. Treatment with meloxicam led to a higher gastric damage than with piroxicam on day 14 although these results were not significant. The levels of myeloperoxidase activity (as an index of neutrophil infiltration) were not changed compared with control after drug treatment. All the hematological parameters obtained after drugs administration for 14 and 28 days were in the range of normal values, and a significant increase in platelet levels could be observed in the group treated with 5 mg/kg of piroxicam for 14 days. Aspartate aminotransferase (AST or GOT) increased significantly after 14 days, but after 28 days the values returned to normality. Creatinine and urea did not undergo significant changes except for the piroxicam 14-day 5 mg/kg group, in which uremia increased significantly over normal values. In conclusion, our results show that meloxicam, a preferential COX-2 inhibitor, causes rates of gastric lesion comparable to those seen with traditional NSAIDs, without inducing important changes in biological parameters.

Avaliações hematológicas e bioquímicas do uso de diclofenaco de sódio, meloxicam e firocoxibe em ratos

“…Não houve alterações significativas das plaquetas (Tabelas 1 e 3). Este fato também foi observado em ratos Wistar tratados com meloxicam (3,75 mg/kg, a cada 24 horas, por via intragástrica durante 14 e 28 dias) 10 . Por outro lado, podem ocorrer trombocitopenia com o uso de AINES 1 , contrariando os dados obtidos neste trabalho.…”

Synergistic interaction between meloxicam and aminoguanidine in formalin‐induced nociception in mice

“…Though, there is limited information about GI toxicity of meloxicam in experimental animals (Villegas et al, 2002;Gambero et al, 2005), it has been shown to possess varying degree of GI toxicity in clinical cases (Layton et al, 2003;MacDonald et al, 2003;Laporte et al, 2004;Richy et al, 2004).There is no direct evidence from the present study that aminoguanidine has reduced GI toxicity of meloxicam, but aminoguanidine has been found to be gastroprotective in adjuvant-induced arthritic rats exposed to indomethacin (Kato et al, 1999) and acetic acid-induced ulcers (Akiba et al, 1998). In conclusion, the use of aminoguanidine will help in reducing the dose of meloxicam, showing synergistic antinociceptive effect and might reduce GI toxicity.…”

The effect of oral administration of robenacoxib on hematological and biochemical parameters in different goat breeds

“…Similar to these findings, meloxicam and ketoprofen did not alter the hematological parameters of healthy ponies (Pozzobon et al, 2009). Villegas et al (2002) reported that piroxicam and meloxicam did not significantly affect hematological parameters in rats. Some enzymes, proteins, and nucleic acids in the blood associated with specific tissue damage can be used to detect most drug-related adverse effects and, in some cases, to determine the prognosis (Tang and Lu, 2010;Özdemir and Traş, 2018).…”