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Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages.

dc.contributor.authorMayo Barrallo, Juan Carlos 
dc.contributor.authorSainz Menéndez, Rosa María 
dc.contributor.authorTan, Dun-Xian
dc.contributor.authorHardeland, Rüdiger
dc.contributor.authorLeon, Josefa
dc.contributor.authorRodríguez Sánchez, María del Carmen 
dc.contributor.authorReiter, Russel J.
dc.date.accessioned2024-03-20T08:53:43Z
dc.date.available2024-03-20T08:53:43Z
dc.date.issued2005
dc.identifier.urihttps://hdl.handle.net/10651/72012
dc.description.abstractnflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (iNOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally related compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented iNOS activation and reduced the concentration of products from both enzymes, PGE2 and nitric oxide. Another endogenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and iNOS as molecular targets for either melatonin or its metabolites AFMK and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition.spa
dc.language.isoengspa
dc.relation.ispartofJournal of Neuroimmunology, 165(1-2)spa
dc.rightsCC Reconocimiento – No Comercial – Sin Obra Derivada 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectMelatoninspa
dc.subjectAFMK
dc.subjectAMK
dc.subjectCOX-2
dc.subjectINOS
dc.subjectRaw 264.7 macrophage
dc.subjectLPS
dc.titleAnti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages.spa
dc.typejournal articlespa
dc.identifier.doi10.1016/j.jneuroim.2005.05.002
dc.relation.publisherversionhttps://doi.org/10.1016/j.jneuroim.2005.05.002
dc.rights.accessRightsopen accessspa
dc.type.hasVersionSMURspa


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