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Eur J Pharmacol ; 890: 173670, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33098831

RESUMEN

Potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65) is a potent inhibitor of the uridine phosphorylase 1 (UPP1) enzyme. Its non-ionized analog has already demonstrated biological properties by reducing adverse effects caused by the chemotherapeutic 5-fluorouracil (5-FU). In addition, it has been demonstrated that uridine inhibits inflammation and fibrosis in bleomycin lung injury, decreasing collagen production. The purpose of this study was to investigate the in vitro and in vivo effects of CPBMF65 on activated hepatic stellate cells (HSC) and on carbon tetrachloride-induced liver fibrosis in mice. After incubation with CPBMF65, decreased cell proliferation and phenotype reversion were observed in vitro. In addition, CPBMF65 promoted a protective effect on tetrachloride-induced liver fibrosis in mice, demonstrated by its antifibrotic and anti-inflammatory actions. The results of the present study indicate that the UPP1 inhibitor (CPBMF65) may have potential as a novel therapeutic agent for the treatment of liver fibrosis.


Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Células Estrelladas Hepáticas/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Uridina Fosforilasa/antagonistas & inhibidores , Animales , Tetracloruro de Carbono/toxicidad , Línea Celular Transformada , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Células Estrelladas Hepáticas/enzimología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/enzimología , Masculino , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Uridina Fosforilasa/metabolismo
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