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Melatonin, a "guardian" of the genome and cellular integrity for prevention of photocarcinogenesis
Orientador(es)
Resumo(s)
This review aims to highlight the potential use of melatonin for inhibition and/or repair of oxidative stress and other UV-induced damages in the photocarcinogesis context. Melatonin is a ubiquitous indolamine derived from the amino-acid tryptophan being a widely occurring neurotransmitter-like compound primarily derived from the pineal gland. However, it can be produced in other several organs including the skin and retina. This hormone production follows a circadian light-dependent rhythm of secretion, and therefore it was designed as the "circadian pacemaker". Melatonin exerts different receptor (MT-1, -2, -3; ROR/ RZR) dependent actions, such as: stimulation of antioxidant enzymes (SOD; CAT; GPx); inhibition of prooxidant enzymes and lipid peroxidation; modulation of proteins associated with apoptosis expression or reduction of proinflamatory cytokines. In addition, it has also receptor independent actions, including the direct radical scavenging action. Overall, it has homeostatic functions and a pleiotropic activity working not only as a neurotransmissor, but also as a hormone, cytokine and biological-responser modifier in order to preserve the physical and functional integrity of the organism. These actions are mediated by paracrine, autocrine and antioxidant mechanisms which are not only attributable to melatonin but also to its metabolites generated by three possible pathways (classic, indolic and kynuric) through enzymatic as well as chemical reactions. Regarding the beneficial effects of melatonin on UV- induced skin damages, current data indicate that it acts as a potent antioxidant, anti-apoptotic and anti-inflammatory agent. This cellular protection effect is supported by both in vitro and in vivo results and includes the photoprotection against the sunburn, DNA damage, oxidative stress and immune suppression. This review shows how melatonin can be considered a "guardian" of the genome and cellular integrity for prevention of photocarcinogenesis.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2015
Palavras-chave
Circadian pacemaker Genomic instability Melatonin Mestrado Integrado - 2015 Photocarcinogenesis Photoimmune suppression Radical Scavenger