Heme oxygenase/carbon monoxide-biliverdin pathway may be involved in the antinociceptive activity of etoricoxib, a selective COX-2 inhibitor.
Journal Title: Pharmacological Reports - Year 2011, Vol 63, Issue 1
Abstract
The aim of this study was to assess the interaction between the heme oxygenase-1/ biliverdin/carbon monoxide (HO-1/BVD/CO) and cyclooxygenase-2 (COX-2) pathways in the writhing test. Mice were pretreated with 0.1, 1 or 10 mg/kg, ip etoricoxib, a selective COX-2 inhibitor, or with one of the following HO-1/BVD/CO pathway modulators: 1, 3 or 9 mg/kg, sc ZnPP IX, a specific HO-1 inhibitor, 0.3, 1 or 3 mg/kg, sc hemin, a substrate of the HO-1/BVD/CO pathway; or 0.00025, 0.025 or 2.5 μmol/kg, sc DMDC, a CO donor. Mice pretreated with etoricoxib or one of the HO-1/BVD/CO pathway modulators received an injection of acetic acid (ip) after 30 and 60 min, respectively. Next, the number of writhes was quantified between 0 and 30 min after stimulus injection. In another series of experiments, ineffective doses of etoricoxib were co-administered with hemin or DMDC and an effective dose of etoricoxib with ZnPP IX, followed by an acetic acid injection. Four hours after the acetic acid injection, levels of bilirubin, which is a product of BVD conversion by the BVD reductase enzyme, in the peritoneal lavage were determined. Hemin or DMDC reduced (p<0.05) the number of writhes, but ZnPP IX potentiated (p<0.05) the effect of acetic acid by increasing (p < 0.05) the number of writhes. The co-administration of etoricoxib with hemin or DMDC reduced (p<0.05) the number of writhes. However, the analgesic effect of etoricoxib was not observed in the presence of ZnPP IX. Pretreatment with ZnPP IX reduced bilirubin levels, but etoricoxib pretreatment significantly increased the bilirubin concentration in peritoneal exudates. The data obtained from these experiments showed that the HO-1/BVD/CO pathway was activated in the acetic acid-induced abdominal writhing model. The analgesic effect of etoricoxib was at least partially dependent on the participation of the HO-1/BVD/CO pathway.
Authors and Affiliations
Niedja Grangeiro, Jordana Aguiar, Hellíada Chaves, Antonio Silva, Vilma Lima, Norma Benevides, Gerly Brito, José da Graça, Mirna Bezerra
Keywords
Related Articles
- EP ID EP102772
- DOI -
- Views 86
- Downloads 0
Effects of co-administration of fluoxetine or tianeptine with metyrapone on immobility time and plasma corticosterone concentration in rats subjected to the forced swim test.
Major depression is frequently associated with hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. The aim of the prese...
Hematological effects of exposure to mixtures of selected ethylene glycol alkyl ethers in rats.
Exposure to various ethylene glycol monoalkyl ethers (EGAEs) is known to result in hemolytic effect caused by their metabolites, appropriate alkoxyacetic acids, generated via both alcohol dehydrogenase and aldehyde dehyd...
Betulin, betulinic acid and butein are inhibitors of acetaldehyde-induced activation of liver stellate cells.
Liver fibrosis has been reported to be inhibited in vivo by oleanolic and ursolic acids; however, the activity of other triterpenes like betulin and betulinic acid has not been examined. Butein has also been reported to...
Heme oxygenase/carbon monoxide-biliverdin pathway may be involved in the antinociceptive activity of etoricoxib, a selective COX-2 inhibitor.
The aim of this study was to assess the interaction between the heme oxygenase-1/ biliverdin/carbon monoxide (HO-1/BVD/CO) and cyclooxygenase-2 (COX-2) pathways in the writhing test. Mice were pretreated with 0.1, 1 or 1...
Increases in β-amyloid protein in the hippocampus caused by diabetic metabolic disorder are blocked by minocycline through inhibition of NF-κB pathway activation.
Activation of the NF-κB pathway plays an important role in the pathophysiology of Alzheimer's disease (AD), and blocking NF-κB pathway activation has been shown to attenuate cognitive impairment. Diabetic metabolic disor...