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

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125916

RESUMO

Understanding the role of iron in ethanol-derived hepatic stress could help elucidate the efficacy of dietary or clinical interventions designed to minimize liver damage from chronic alcohol consumption. We hypothesized that normal levels of iron are involved in ethanol-derived liver damage and reduced dietary iron intake would lower the damage caused by ethanol. We used a pair-fed mouse model utilizing basal Lieber-DeCarli liquid diets for 22 weeks to test this hypothesis. In our mouse model, chronic ethanol exposure led to mild hepatic stress possibly characteristic of early-stage alcoholic liver disease, seen as increases in liver-to-body weight ratios. Dietary iron restriction caused a slight decrease in non-heme iron and ferritin (FeRL) expression while it increased transferrin receptor 1 (TfR1) expression without changing ferroportin 1 (FPN1) expression. It also elevated protein lysine acetylation to a more significant level than in ethanol-fed mice under normal dietary iron conditions. Interestingly, iron restriction led to an additional reduction in nicotinamide adenine dinucleotide (NAD+) and NADH levels. Consistent with this observation, the major mitochondrial NAD+-dependent deacetylase, NAD-dependent deacetylase sirtuin-3 (SIRT3), expression was significantly reduced causing increased protein lysine acetylation in ethanol-fed mice at normal and low-iron conditions. In addition, the detection of superoxide dismutase 1 and 2 levels (SOD1 and SOD2) and oxidative phosphorylation (OXPHOS) complex activities allowed us to evaluate the changes in antioxidant and energy metabolism regulated by ethanol consumption at normal and low-iron conditions. We observed that the ethanol-fed mice had mild liver damage associated with reduced energy and antioxidant metabolism. On the other hand, iron restriction may exacerbate certain activities of ethanol further, such as increased protein lysine acetylation and reduced antioxidant metabolism. This metabolic change may prove a barrier to the effectiveness of dietary reduction of iron intake as a preventative measure in chronic alcohol consumption.


Assuntos
Antioxidantes , Metabolismo Energético , Etanol , Animais , Camundongos , Acetilação/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Antioxidantes/metabolismo , Masculino , Ferro/metabolismo , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase/metabolismo , Lisina/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Receptores da Transferrina/metabolismo , Sirtuína 3/metabolismo , Sirtuína 3/genética , NAD/metabolismo , Ferritinas/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/etiologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa