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Métodos Terapéuticos y Terapias MTCI
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1.
Oxid Med Cell Longev ; 2019: 3527809, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31428222

RESUMEN

Alcohol abuse has become common worldwide and has been recognized as a major cause of chronic alcoholic liver disease (ALD). ALD encompasses a complex process that includes a broad scope of hepatic lesions, ranging from steatosis to cirrhosis. In particular, reactive oxygen species (ROS) are mainly involved. Numerous studies have shown that p66shc plays a significant role in ALD. Protocatechuic acid (PCA), a dihydroxybenzoic acid that is naturally found in green tea, vegetables, and fruits, has efficient free radical scavenging effects. In this study, we aimed to assess the protective effect of PCA on ALD and to evaluate the microRNA- (miRNA-) p66shc-mediated reduction of ROS formation in ALD. Our results demonstrated that PCA treatment significantly decreased p66shc expression and downstream ROS formation in ALD. miR-219a-5p, which was identified by bioinformatics and experimental analysis, was enhanced by PCA and subsequently suppressed p66shc expression. Importantly, p66shc played an essential role in the protection of PCA-stimulated miR-219a-5p overexpression. Overall, these findings show that PCA-stimulated miR-219a-5p expression mitigates ALD by reducing p66shc-mediated ROS formation. This study may contribute to the development of therapeutic interventions for ALD.


Asunto(s)
Hidroxibenzoatos/farmacología , Hepatopatías Alcohólicas/tratamiento farmacológico , MicroARNs/metabolismo , Sustancias Protectoras/uso terapéutico , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/metabolismo , Regiones no Traducidas 3' , Animales , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Etanol/toxicidad , Glutatión/metabolismo , Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hidroxibenzoatos/uso terapéutico , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , Masculino , Ratones , MicroARNs/química , Sustancias Protectoras/farmacología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/química , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/genética , Superóxido Dismutasa/metabolismo
2.
Toxicol Appl Pharmacol ; 350: 21-31, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29729281

RESUMEN

In recent years, alcoholic liver disease (ALD) has emerged as a growing public health problem worldwide. ß-catenin plays an important role in the growth, development, regeneration and metabolic activity of the liver. Salvianolic acid A (SalA) is a water-soluble component from the root extract of Salvia miltiorrhiza Bunge, and its effect on ALD has not yet been investigated. This study aimed to investigate the effect of SalA on chronic alcohol-induced liver injury and to explore the role of SIRT1-mediated ß-catenin deacetylation in such an effect. In this study, SalA treatment significantly alleviated the accumulation of lipid droplets and reduced the plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), alcohol and ammonia levels in rats. SalA enhanced ethanol and ammonia metabolism and maintained mitochondrial homeostasis. Moreover, SalA restored the activity of the major ethanol-metabolizing enzymes and oxidative stress functions in the liver. Importantly, we found that SalA treatment effectively inhibited the ethanol-mediated decrease in nuclear ß-catenin by upregulating SIRT1 in the liver. SIRT1 then deacetylated ß-catenin to promote its accumulation in the nucleus, thereby preventing alcohol-induced liver injury. The results demonstrate that the SIRT1/ß-catenin pathway is a key therapeutic target in liver injury caused by chronic alcohol exposure and that SalA protects against alcohol-induced liver injury via the SIRT1-mediated deacetylation of ß-catenin.


Asunto(s)
Ácidos Cafeicos/uso terapéutico , Nucléolo Celular/metabolismo , Lactatos/uso terapéutico , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/metabolismo , Sirtuina 1/metabolismo , beta Catenina/metabolismo , Animales , Ácidos Cafeicos/farmacología , Nucléolo Celular/efectos de los fármacos , Enfermedad Crónica , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Lactatos/farmacología , Hepatopatías Alcohólicas/patología , Masculino , Ratones , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/uso terapéutico , Ratas , Ratas Sprague-Dawley
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