The antiinflammatory action of guanabenz is mediated through 5-lipoxygenase and cyclooxygenase inhibition |
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| Institution: | 1. Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925, Alcorcón, Madrid, Spain;2. Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925, Alcorcón, Madrid, Spain;1. Department of Neurology, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts;2. Department of Neurology, Harvard Medical School, Boston, Massachusetts;3. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts;1. Pharmacology lab, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain;2. Institute of Psychiatry, Psychology and Neuroscience, Division of Academic Psychiatry London, Kings College London, London, UK;3. Department of Biochemistry & Physiology, Faculty of Health & Medical Sciences, University of Surrey, Guildford, UK;4. Institute of Medical and Biomedical Education, St George׳s University of London, London SW17 0RE, UK;5. BRAINco Biopharma, S.L., Bizkaia Technology Park, Spain;1. Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China;2. Guangzhou Institute of Pediatrics, Guangzhou Women and Children Medical Center, Guangzhou, 510623, China;3. University of Chinese Academy of Sciences, Beijing, 100049, China;4. State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, China;1. Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea;2. Department of Pathology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea;3. Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;4. Departments of Radiology and Cancer Systems Imaging, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA |
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| Abstract: | Guanabenz (2,6-dichlorobenzylidene amino guanidine acetate), an α2-agonist, possesses antiinflammatory substances, the effect of guanabenz on LT and Since leukotrienes (LT) and prostaglandins(PG) are proinflammatory substances, the effect of guanabenz on LT and PG synthesis by inflammatory cells was investigated. Guanabenz, but not clonidine, B-HT 920 or B-HT 933 inhibited zymosan-induced LTC4 (IC50=13 μM) and PGE2 (IC50=10.9 μM) synthesis with no concomitant reduction in zymosan phagocytosis or cell viability. Similarlyguanabenz reduced LTB4 (IC50=37.4 μM) and PGE2 (IC50=13.8 μM) synthesis by A23187-stimulated rat glycogen elicited neutrophils. Furthermore, guanabenz did not inhibit platelet 12-lipoxygenase or phospholipase A2. In vivo, guanabenz was orally active against rat carrageenan paw edema and adjuvant arthritis (ED50s=9 and 10 mg/kg, respectively). Topically applied guanabenz reduced arachidonic acid (AA)- or tetradecanoyl phorbol acetate (TPA)-induced ear inflammation (ED50s:AAA-induced ear edema, 1.4 mg/ear; PMA-induced ear edema, 0.013 mg/ear). Therefore, the antiinflammatory activity of guanabenz may be due to its ability to inhibit the formation of 5-lipoxygenase and cyclooxygenase products. |
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