Chronic leukotriene inhibition in the rat fails to modify the toxicological effects of a cyclooxygenase inhibitor
| Autor: | C. P. Peter, P. Tagari, Anthony W. Ford-Hutchinson, J. B. Coleman, S. V. Ching, C. A. Anderson |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Leukotrienes medicine.medical_specialty Indoles Gastrointestinal Diseases Physiology medicine.medical_treatment Indomethacin Prostaglandin Pharmacology chemistry.chemical_compound Physiology (medical) Internal medicine Animals Medicine Cyclooxygenase Inhibitors Lipoxygenase Inhibitors Leukotriene Chemotherapy Arachidonic Acid Nonsteroidal biology business.industry Stomach Body Weight General Medicine Rats medicine.anatomical_structure Endocrinology chemistry Toxicity biology.protein Leukotriene Antagonists Cyclooxygenase business Ex vivo |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 71:806-810 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y93-120 |
| Popis: | A 5-week study was carried out in rats using a leukotriene biosynthesis inhibitor (MK-886; 3-[1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid) at a dose of 300 mg∙kg−1∙day−1, this being sufficient to produce > 90% inhibition of ex vivo leukotriene B4 synthesis in rat blood, and a cyclooxygenase inhibitor (indomethacin, 4 and 6 mg∙kg−1∙day−1) to ascertain whether inhibition of leukotriene biosynthesis would potentiate or inhibit the toxicity associated with the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), in particular the gastrointestinal damage. Treatment with indomethacin alone or in combination with MK-886 resulted in the toxicity normally associated with NSAIDs, including gastrointestinal lesions. No toxicity was associated with the administration of MK-886 alone, and MK-886 had no significant effect on the incidence of gastrointestinal lesions produced by indomethacin. These results indicate that leukotrienes are not significant mediators of NSAID-induced gastroenteropathy in the rat.Key words: nonsteroidal anti-inflammatory drugs, gastric damage, gastropathy, leukotrienes, prostaglandins. |
| Databáze: | OpenAIRE |
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