European journal of pharmacology · 2020
Therapeutic effect of uridine phosphorylase 1 (UPP1) inhibitor on liver fibrosis in vitro and in vivo.
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Gonçalves da Silva Elisa Feller, Costa Bruna Pasqualotto, Nassr Marcella Tornquist, de Souza Basso Bruno, Bastos Matheus Scherer, Antunes Géssica Luana, Reghelin Camille Kirinus, Rosa Garcia Maria Claudia, Schneider Levorse Vitor Giancarlo, Carlessi Leonardo Pfeiff, Antunes Fernandes Krist Helen, Richter Schmitz Carine Raquel, Haute Gabriela Viegas, Luft Carolina, Santarém Eliane, Barbé-Tuana Florencia María, Donadio Márcio Vinícius Fagundes, Basso Luiz Augusto, Machado Pablo, Rodrigues de Oliveira Jarbas
Аннотация
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.