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Eur J Pharmacol ; 890: 173670, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33098831

RESUMO

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.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Uridina Fosforilase/antagonistas & inibidores , Animais , Tetracloreto de Carbono/toxicidade , Linhagem Celular Transformada , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Células Estreladas do Fígado/enzimologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Uridina Fosforilase/metabolismo
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