Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was aimed to evaluate the anti-inflammatory potential of triterpene alpha, beta-amyrin in rats on acute phase periodontitis. Periodontitis was induced by ligature placement around the maxillary right second molar tooth. Rats (n = 8/group) were pretreated with alpha, beta-amyrin (5 and 10 mg/kg, p. o.), two hours before the induction of periodontal inflammation. Sham-operated and positive controls (lumiracoxib and dexamethasone) were included. Six hours later, plasma levels of TNF-alpha were analysed. Rats were sacrificed at 24 h, and the gingival tissue analysed for myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBARS), as measures of neutrophil influx and lipid-peroxidation, respectively alpha, beta-Amyrin as well as dexamethasone significantly inhibited the periodontitis-associated increases of TNF-alpha, and the gingival MPO and TBARS. alpha, beta-Amyrin effect was more prominent at 5 mg/kg. Lumiracoxib manifested varied influence on the studied parameters. These results provide evidence to show that alpha, beta-Amyrin retards acute inflammation in rat model of periodontitis and warrant further study on its efficacy to prevent chronic periodontitis-associated bone loss.
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PMID:Anti-inflammatory effect of alpha, beta-Amyrin, a pentacyclic triterpene from Protium heptaphyllum in rat model of acute periodontitis. 1804 12

Lumiracoxib (Prexige; 2-[(2-fluoro-6-chlorophenyl)amino]-5-methyl-benzeneacetic acid) is a cyclooxygenase-2 selective inhibitor for the symptomatic treatment of osteoarthritis. Recently, the drug has been withdrawn in several countries due to serious liver side effects. Li et al. recently have shown that lumiracoxib is bioactivated to a proposed quinone imine that is trapped by N-acetylcysteine (NAC) to form two NAC adducts in human and rat liver microsomal incubations. The current study demonstrated that the lumiracoxib metabolite 4'-hydroxylumiracoxib (M5) can also be bioactivated by peroxidases such as horseradish peroxidase, myeloperoxidase, and prostaglandin H synthases. Efforts were also made to identify GSH adducts formed by P450s in human liver microsomal incubations of lumiracoxib. We herein report the detection and characterization of mono-, di-, tri-, and tetra-GSH adducts in these oxidizing systems. Most of the conjugates were generated as a result of bioactivation of M5 by both peroxidases and P450s. Quinone imine (M15) and two GSH-conjugated quinone imines (M17 and M18) were identified as intermediates in the formation of these conjugates. The latter two were formed through sequential elimination of the fluorine and chlorine groups of GSH-conjugated M15. An additional GSH adduct, which appeared to be formed directly from parent, was only observed in human liver microsomal incubations. A mechanism was proposed for the bioactivation of lumiracoxib and the formation of the observed GSH adducts. These results suggest that bioactivation of lumiracoxib and M5 may result in GSH depletion, covalent binding to proteins, and oxidative stress and may potentially lead to hepatotoxicity.
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PMID:Bioactivation of lumiracoxib by peroxidases and human liver microsomes: identification of multiple quinone imine intermediates and GSH adducts. 1906 90