Mecanismo de Hepatotoxicidade do Paracetamol

• Autor(a) principal: Miguel António Mendes Pereira
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://repositorio-aberto.up.pt/handle/10216/114357
• topic: Medicina básica; Basic medicine

Acetaminophen or paracetamol overdose is a main cause of acute liver failure, however the precise hepatotoxicity's mechanism of this medicine still has questions to be answered.In acetaminophen overdose, is formed one extremely reactive metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), which accumulates so much that overcome the capacity of the inactivation pathways, in the hepatocytes. NAPQI is particularly toxic to mitochondria, uncoupling the respiratory chain, leading to oxidative stress and mitochondrial dysfunction. The dysfunction of this organelles, combined with the associated nuclear fragmentation, culminates in hepatocyte necrosis. Meanwhile, oxidative stress activates metabolic pathways such as c-jun-N-terminal kinase (JNK), p53, mitochondrial fission, endoplasmic reticulum stress and increasing cytoplasmic calcium, which promotes acetaminophen hepatic toxicity, on the other hand, metabolic pathways such as nuclear factor-like 2 (Nrf2) and mitophagy, that have demonstrated a contrarregulatory role of this mechanism.Next to hepatocyte necrosis, the immune system is called to intervene and each one of the cells types could have a damaging or a protecting role on the liver failure.