Your browser doesn't support javascript.
loading
Targeting Oxidative Stress for the Treatment of Liver Fibrosis.
Luangmonkong, Theerut; Suriguga, Su; Mutsaers, Henricus A M; Groothuis, Geny M M; Olinga, Peter; Boersema, Miriam.
Afiliação
  • Luangmonkong T; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
  • Suriguga S; Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
  • Mutsaers HAM; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
  • Groothuis GMM; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
  • Olinga P; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Boersema M; Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, Groningen, The Netherlands.
Rev Physiol Biochem Pharmacol ; 175: 71-102, 2018.
Article em En | MEDLINE | ID: mdl-29728869
Oxidative stress is a reflection of the imbalance between the production of reactive oxygen species (ROS) and the scavenging capacity of the antioxidant system. Excessive ROS, generated from various endogenous oxidative biochemical enzymes, interferes with the normal function of liver-specific cells and presumably plays a role in the pathogenesis of liver fibrosis. Once exposed to harmful stimuli, Kupffer cells (KC) are the main effectors responsible for the generation of ROS, which consequently affect hepatic stellate cells (HSC) and hepatocytes. ROS-activated HSC undergo a phenotypic switch and deposit an excessive amount of extracellular matrix that alters the normal liver architecture and negatively affects liver function. Additionally, ROS stimulate necrosis and apoptosis of hepatocytes, which causes liver injury and leads to the progression of end-stage liver disease. In this review, we overview the role of ROS in liver fibrosis and discuss the promising therapeutic interventions related to oxidative stress. Most importantly, novel drugs that directly target the molecular pathways responsible for ROS generation, namely, mitochondrial dysfunction inhibitors, endoplasmic reticulum stress inhibitors, NADPH oxidase (NOX) inhibitors, and Toll-like receptor (TLR)-affecting agents, are reviewed in detail. In addition, challenges for targeting oxidative stress in the management of liver fibrosis are discussed.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espécies Reativas de Oxigênio / Estresse Oxidativo / Hepatócitos / Células Estreladas do Fígado / Cirrose Hepática Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espécies Reativas de Oxigênio / Estresse Oxidativo / Hepatócitos / Células Estreladas do Fígado / Cirrose Hepática Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article