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Mol Immunol ; 170: 60-75, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38626622

RESUMEN

Liver diseases caused by viral infections, alcoholism, drugs, or chemical poisons are a significant health problem: Liver diseases are a leading contributor to mortality, with approximately 2 million deaths per year worldwide. Liver fibrosis, as a common liver disease characterized by excessive collagen deposition, is associated with high morbidity and mortality, and there is no effective treatment. Numerous studies have shown that the accumulation of mast cells (MCs) in the liver is closely associated with liver injury caused by a variety of factors. This study investigated the relationship between MCs and carbon tetrachloride (CCl4)-induced liver fibrosis in rats and the effects of the MC stabilizers sodium cromoglycate (SGC) and ketotifen (KET) on CCl4-induced liver fibrosis. The results showed that MCs were recruited or activated during CCl4-induced liver fibrosis. Coadministration of SCG or KET alleviated the liver fibrosis by decreasing SCF/c-kit expression, inhibiting the TGF-ß1/Smad2/3 pathway, depressing the HIF-1a/VEGF pathway, activating Nrf2/HO-1 pathway, and increasing the hepatic levels of GSH, GSH-Px, and GR, thereby reducing hepatic oxidative stress. Collectively, recruitment or activation of MCs is linked to liver fibrosis and the stabilization of MCs may provide a new approach to the prevention of liver fibrosis.


Asunto(s)
Tetracloruro de Carbono , Cromolin Sódico , Cirrosis Hepática , Hígado , Mastocitos , Animales , Mastocitos/metabolismo , Mastocitos/inmunología , Mastocitos/efectos de los fármacos , Tetracloruro de Carbono/toxicidad , Ratas , Masculino , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/inmunología , Cirrosis Hepática/inducido químicamente , Cromolin Sódico/farmacología , Hígado/patología , Hígado/metabolismo , Hígado/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Ratas Sprague-Dawley , Cetotifen/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Estrés Oxidativo/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
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