Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Toxicol Appl Pharmacol ; 329: 259-271, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28624444

RESUMO

Dinoseb is a highly toxic pesticide of the dinitrophenol group. Its use has been restricted, but it can still be found in soils and waters in addition to being a component of related pesticides that, after ingestion by humans or animals, can originate the compound by enzymatic hydrolysis. As most dinitrophenols, dinoseb uncouples oxidative phosphorylation. In this study, distribution, lipid bilayer affinity and kinetics of the metabolic effects of dinoseb were investigated, using mainly the isolated perfused rat liver, but also isolated mitochondria and molecular dynamics simulations. Dinoseb presented high affinity for the hydrophobic region of the lipid bilayers, with a partition coefficient of 3.75×104 between the hydrophobic and hydrophilic phases. Due to this high affinity for the cellular membranes dinoseb underwent flow-limited distribution in the liver. Transformation was slow but uptake into the liver space was very pronounced. For an extracellular concentration of 10µM, the equilibrium intracellular concentration was equal to 438.7µM. In general dinoseb stimulated catabolism and inhibited anabolism. Half-maximal stimulation of oxygen uptake in the whole liver occurred at concentrations (2.8-5.8µM) at least ten times above those in isolated mitochondria (0.28µM). Gluconeogenesis and ureagenesis were half-maximally inhibited at concentrations between 3.04 and 5.97µM. The ATP levels were diminished, but differently in livers from fed and fasted rats. Dinoseb disrupts metabolism in a complex way at concentrations well above its uncoupling action in isolated mitochondria, but still at concentrations that are low enough to be dangerous to animals and humans even at sub-lethal doses.


Assuntos
2,4-Dinitrofenol/análogos & derivados , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Metabolismo Energético/efeitos dos fármacos , Fígado/efeitos dos fármacos , Praguicidas/toxicidade , 2,4-Dinitrofenol/química , 2,4-Dinitrofenol/toxicidade , Trifosfato de Adenosina/metabolismo , Animais , Transporte Biológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Frutose/metabolismo , Gluconeogênese/efeitos dos fármacos , Glicogênio/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Cinética , Ácido Láctico/metabolismo , Bicamadas Lipídicas , Fígado/metabolismo , Fígado/patologia , Masculino , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Modelos Biológicos , Simulação de Dinâmica Molecular , Fosforilação Oxidativa/efeitos dos fármacos , Praguicidas/química , Ratos Wistar , Medição de Risco , Ureia/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...