Therapeutic effect of uridine phosphorylase 1 (UPP1) inhibitor on liver fibrosis in vitro and in vivo
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 additi...
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| creator | 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 |
| description | 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.
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| doi_str_mv | 10.1016/j.ejphar.2020.173670 |
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[Display omitted]</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2020.173670</identifier><identifier>PMID: 33098831</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Antifibrotic ; Carbon Tetrachloride - toxicity ; Cell Line, Transformed ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Enzyme Inhibitors - therapeutic use ; Hepatic stellate cells ; Hepatic Stellate Cells - drug effects ; Hepatic Stellate Cells - enzymology ; Liver Cirrhosis - chemically induced ; Liver Cirrhosis - drug therapy ; Liver Cirrhosis - enzymology ; Liver Cirrhosis - pathology ; Liver fibrosis ; Male ; Mice ; Mice, Inbred BALB C ; Random Allocation ; Uridine Phosphorylase - antagonists & inhibitors ; Uridine Phosphorylase - metabolism ; Uridine phosphorylase 1</subject><ispartof>European journal of pharmacology, 2021-01, Vol.890, p.173670-173670, Article 173670</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-3f9f74c0d67eb4d156aec1005cb5203bf1f6601c6b63716b3dea53c2766c312a3</citedby><cites>FETCH-LOGICAL-c474t-3f9f74c0d67eb4d156aec1005cb5203bf1f6601c6b63716b3dea53c2766c312a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2020.173670$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33098831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gonçalves da Silva, Elisa Feller</creatorcontrib><creatorcontrib>Costa, Bruna Pasqualotto</creatorcontrib><creatorcontrib>Nassr, Marcella Tornquist</creatorcontrib><creatorcontrib>de Souza Basso, Bruno</creatorcontrib><creatorcontrib>Bastos, Matheus Scherer</creatorcontrib><creatorcontrib>Antunes, Géssica Luana</creatorcontrib><creatorcontrib>Reghelin, Camille Kirinus</creatorcontrib><creatorcontrib>Rosa Garcia, Maria Claudia</creatorcontrib><creatorcontrib>Schneider Levorse, Vitor Giancarlo</creatorcontrib><creatorcontrib>Carlessi, Leonardo Pfeiff</creatorcontrib><creatorcontrib>Antunes Fernandes, Krist Helen</creatorcontrib><creatorcontrib>Richter Schmitz, Carine Raquel</creatorcontrib><creatorcontrib>Haute, Gabriela Viegas</creatorcontrib><creatorcontrib>Luft, Carolina</creatorcontrib><creatorcontrib>Santarém, Eliane</creatorcontrib><creatorcontrib>Barbé-Tuana, Florencia María</creatorcontrib><creatorcontrib>Donadio, Márcio Vinícius Fagundes</creatorcontrib><creatorcontrib>Basso, Luiz Augusto</creatorcontrib><creatorcontrib>Machado, Pablo</creatorcontrib><creatorcontrib>Rodrigues de Oliveira, Jarbas</creatorcontrib><title>Therapeutic effect of uridine phosphorylase 1 (UPP1) inhibitor on liver fibrosis in vitro and in vivo</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>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.
[Display omitted]</description><subject>Animals</subject><subject>Antifibrotic</subject><subject>Carbon Tetrachloride - toxicity</subject><subject>Cell Line, Transformed</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Hepatic stellate cells</subject><subject>Hepatic Stellate Cells - drug effects</subject><subject>Hepatic Stellate Cells - enzymology</subject><subject>Liver Cirrhosis - chemically induced</subject><subject>Liver Cirrhosis - drug therapy</subject><subject>Liver Cirrhosis - enzymology</subject><subject>Liver Cirrhosis - pathology</subject><subject>Liver fibrosis</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Random Allocation</subject><subject>Uridine Phosphorylase - antagonists & inhibitors</subject><subject>Uridine Phosphorylase - metabolism</subject><subject>Uridine phosphorylase 1</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1P3DAQhi1UBMvHP0DIRzhk8diOvbkgIVRKJaRygLPlOGOtV9k4tZOV-Pc1Cu2xh9FoZt75egi5ArYGBuput8bduLVpzRkvKS2UZkdkBRvdVEwD_0ZWjIGseNM0p-Qs5x1jrG54fUJOhWDNZiNgRfBti8mOOE_BUfQe3USjp3MKXRiQjtuYi6WP3makQG_eX1_hloZhG9owxUTjQPtwwER9aFPMIZcaPYQpRWqHbgkO8YIce9tnvPzy5-T96fvb43P18uvHz8eHl8pJLadK-MZr6VinNLayg1pZdFCudm3NmWg9eKUYONUqoUG1okNbC8e1Uk4At-Kc3CxzxxR_z5gnsw_ZYd_bAeOcDZe1BMmk0EUqF6krZ-eE3owp7G36MMDMJ2CzMwtg8wnYLIBL2_XXhrndY_ev6S_RIrhfBFj-PARMJruAg8MupALXdDH8f8MfNS-NrQ</recordid><startdate>20210105</startdate><enddate>20210105</enddate><creator>Gonçalves da Silva, Elisa Feller</creator><creator>Costa, Bruna Pasqualotto</creator><creator>Nassr, Marcella Tornquist</creator><creator>de Souza Basso, Bruno</creator><creator>Bastos, Matheus Scherer</creator><creator>Antunes, Géssica Luana</creator><creator>Reghelin, Camille Kirinus</creator><creator>Rosa Garcia, Maria Claudia</creator><creator>Schneider Levorse, Vitor Giancarlo</creator><creator>Carlessi, Leonardo Pfeiff</creator><creator>Antunes Fernandes, Krist Helen</creator><creator>Richter Schmitz, Carine Raquel</creator><creator>Haute, Gabriela Viegas</creator><creator>Luft, Carolina</creator><creator>Santarém, Eliane</creator><creator>Barbé-Tuana, Florencia María</creator><creator>Donadio, Márcio Vinícius Fagundes</creator><creator>Basso, Luiz Augusto</creator><creator>Machado, Pablo</creator><creator>Rodrigues de Oliveira, Jarbas</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20210105</creationdate><title>Therapeutic effect of uridine phosphorylase 1 (UPP1) inhibitor on liver fibrosis in vitro and in vivo</title><author>Gonçalves da Silva, Elisa Feller ; 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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.
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| subjects | Animals Antifibrotic Carbon Tetrachloride - toxicity Cell Line, Transformed Dose-Response Relationship, Drug Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Enzyme Inhibitors - therapeutic use Hepatic stellate cells Hepatic Stellate Cells - drug effects Hepatic Stellate Cells - enzymology Liver Cirrhosis - chemically induced Liver Cirrhosis - drug therapy Liver Cirrhosis - enzymology Liver Cirrhosis - pathology Liver fibrosis Male Mice Mice, Inbred BALB C Random Allocation Uridine Phosphorylase - antagonists & inhibitors Uridine Phosphorylase - metabolism Uridine phosphorylase 1 |
| title | Therapeutic effect of uridine phosphorylase 1 (UPP1) inhibitor on liver fibrosis in vitro and in vivo |
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