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Advisor(s)
Abstract(s)
A niacina, também conhecida como “vitamina B3” ou “vitamina PP”, abrange duas vitaminas (ácido nicotínico e nicotinamida) na origem das coenzimas: nicotinamida adenina dinucleotídeo (NAD+ ) e nicotinamida adenina dinucleotídeo fosfato (NADP+ ). As duas coenzimas (formas oxidada e reduzida) são cruciais para o equilíbrio redox e para a produção de energia, mas também são substratos para enzimas envolvidas em vias de sinalização nãoredox, regulando assim funções biológicas, incluindo expressão genética, progressão do ciclo celular, reparação de DNA e morte celular. As fontes de Niacina podem ser exógenas (dieta ou suplementação terapêutica) ou endógenas (biossíntese a partir de um precursor). Dependendo se o seu aporte consegue ou não suprir as exigências metabólicas no Homem, podem gerar-se situações de deficiência no organismo humano, com maior ou menor gravidade clínica. Parece existir uma predominância de ácido nicotínico nas plantas, enquanto que nos animais predomina a nicotinamida. As vias metabólicas da niacina e seus derivados são complexas e ainda não completamente elucidadas. As respectivas propriedades farmacológicas são relevantes e numerosas, desde a prevenção da pelagra até ao cancro. Os níveis de NAD+ diminuem ao longo da idade, tendo como consequência um desequilíbrio na homeostasia do organismo levando ao aumento da suscetibilidade à doença. Este fato leva a pensar que a restauração dos níveis de NAD+ poderá prolongar os anos de vida saudável. A forma mais óbvia de aumentar o NAD+ seria a suplementação dos seus percursores. Existem trabalhos científicos importantes que demonstram e evidenciam como a Niacina é indispensável para a Saúde humana. Este trabalho de revisão irá focar a interação entre a niacina e seus derivados com as patologias em causa, revendo os principais trabalhos sobre os papéis da Niacina como agente anti-pelagra, hipolipemiante, neuroprotetor, antienvelhecimento, anti-inflamatório, pleiotrópico na progressão da doença renal crónica, na regressão da esteatose e importante no tratamento do cancro. A monografia contribui para esclarecer os mecanismos moleculares e farmacoterapêuticos da niacina e seus derivados, baseando-se em evidências clínicas e bioquímicas.
Niacin, also known as “vitamin B3” or “vitamin PP”, comprise two vitamins (nicotinic acid and nicotinamide) giving rise to the coenzyme forms: nicotinamide adenine dinucleotide (NAD+ ) and nicotinamide adenine dinucleotide phosphate (NADP+ ). Both coenzymes (oxidized and reduced forms) are crucial for redox balance and for energy production, but are also substrates for enzymes involved in non-redox signaling pathways, thereby regulating biological functions, including gene expression, cell cycle progression, DNA repair, and cell death. Niacin sources may be exogenous (diet or therapeutic supplement) or endogenous (biosynthesis from a precursor). Depending on whether or not its contribution can meet the metabolic requirements in humans, situations of deficiency in the human organism may be generated, with greater or lesser clinical severity. There appears to be a predominance of nicotinic acid in plants, while nicotinamide predominates in animals. The metabolic pathways of niacin and derivatives are complex and not yet fully elucidated. The pharmacological properties of this vitamin are relevant and numerous, from prevention of pellagra to cancer. NAD + levels decrease with age, resulting in an imbalance in the body's homeostasis leading to increased susceptibility to disease. This leads one to think that restoring NAD + levels may prolong healthy years of life. The most obvious way to increase NAD + would be to supplement its precursors. There are important scientific exidences that demonstrate how indispensable Niacin is for human health. The present work will focus on the interactions between niacin and its derivatives with the pathologies concerned, reviewing the main data on the roles of Niacin as an anti-pellagra, hypolipidemic, neuroprotective, anti-aging, antiinflammatory and pleiotropic agent for chronic kidney disease, steatosis regression and for cancer treatment. The monograph will contribute to clarify the molecular and pharmacotherapeutic mechanisms of niacin and its derivatives, based on clinical and biochemical evidence.
Niacin, also known as “vitamin B3” or “vitamin PP”, comprise two vitamins (nicotinic acid and nicotinamide) giving rise to the coenzyme forms: nicotinamide adenine dinucleotide (NAD+ ) and nicotinamide adenine dinucleotide phosphate (NADP+ ). Both coenzymes (oxidized and reduced forms) are crucial for redox balance and for energy production, but are also substrates for enzymes involved in non-redox signaling pathways, thereby regulating biological functions, including gene expression, cell cycle progression, DNA repair, and cell death. Niacin sources may be exogenous (diet or therapeutic supplement) or endogenous (biosynthesis from a precursor). Depending on whether or not its contribution can meet the metabolic requirements in humans, situations of deficiency in the human organism may be generated, with greater or lesser clinical severity. There appears to be a predominance of nicotinic acid in plants, while nicotinamide predominates in animals. The metabolic pathways of niacin and derivatives are complex and not yet fully elucidated. The pharmacological properties of this vitamin are relevant and numerous, from prevention of pellagra to cancer. NAD + levels decrease with age, resulting in an imbalance in the body's homeostasis leading to increased susceptibility to disease. This leads one to think that restoring NAD + levels may prolong healthy years of life. The most obvious way to increase NAD + would be to supplement its precursors. There are important scientific exidences that demonstrate how indispensable Niacin is for human health. The present work will focus on the interactions between niacin and its derivatives with the pathologies concerned, reviewing the main data on the roles of Niacin as an anti-pellagra, hypolipidemic, neuroprotective, anti-aging, antiinflammatory and pleiotropic agent for chronic kidney disease, steatosis regression and for cancer treatment. The monograph will contribute to clarify the molecular and pharmacotherapeutic mechanisms of niacin and its derivatives, based on clinical and biochemical evidence.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Keywords
Niacina NAD+ Vitamina B3 Farmacoterapia Metabolismo Mestrado Integrado - 2019