Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis
Liver fibrosis is defined as excessive extracellular matrix deposition in the hepatic parenchyma as a consequence of complex interactions among matrix-producing hepatic stellate cells (HSCs) and liver-resident and infiltrating cells. In addition to the liver, the process of fibrosis may represent en...
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MDPI AG
2020-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/18/4310 |
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| author | Antonio Pesce Rosella Ciurleo Alessia Bramanti Eliana Concetta Armeli Iapichino Maria Cristina Petralia Gaetano Giuseppe Magro Paolo Fagone Placido Bramanti Ferdinando Nicoletti Katia Mangano |
| author_facet | Antonio Pesce Rosella Ciurleo Alessia Bramanti Eliana Concetta Armeli Iapichino Maria Cristina Petralia Gaetano Giuseppe Magro Paolo Fagone Placido Bramanti Ferdinando Nicoletti Katia Mangano |
| author_sort | Antonio Pesce |
| collection | DOAJ |
| description | Liver fibrosis is defined as excessive extracellular matrix deposition in the hepatic parenchyma as a consequence of complex interactions among matrix-producing hepatic stellate cells (HSCs) and liver-resident and infiltrating cells. In addition to the liver, the process of fibrosis may represent end-stage disease of several diseases including kidneys, lungs, spleens, heart, muscles and at certain extent, the central nervous system and the peripheral nerves. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development. The aim of the present study was to test the efficacy of a new drug combination for the treatment of hepatic fibrosis in order to provide a proof-of-concept for the use of therapeutic agents in clinical practice. For this purpose, we have studied the effects of the PDGF inhibitor imatinib and the angiogenesis inhibitor sorafenib, administered alone or in combination, in reducing the progression of the fibrogenetic process in a pre-clinical model of liver damage induced in mice by repeated administration of Concanavalin A (ConA), resembling long-tern autoimmune hepatitis. Our results suggest that treatments with imatinib and sorafenib can modulate potently and, in a superimposable fashion, the fibrinogenic process when administered alone. However, and in agreement with the computational data presently generated, they only exert partial overlapping antifibrotic effects in modulating the main pathways involved in the process of liver fibrosis, without significant additive or synergist effects, when administered in combination. |
| first_indexed | 2024-03-10T16:11:32Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T16:11:32Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4e8be4033fcf439a9f6f3a1cfea9be5b2023-11-20T14:23:05ZengMDPI AGMolecules1420-30492020-09-012518431010.3390/molecules25184310Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver FibrosisAntonio Pesce0Rosella Ciurleo1Alessia Bramanti2Eliana Concetta Armeli Iapichino3Maria Cristina Petralia4Gaetano Giuseppe Magro5Paolo Fagone6Placido Bramanti7Ferdinando Nicoletti8Katia Mangano9Department of Medical and Surgical Sciences and Advanced Technology G.F. Ingrassia, University of Catania, Via Santa Sofia 86, 95123 Catania, ItalyIRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyIRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyValdese Hospital, Via Silvio Pellico 19, 10125 Torino, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyDepartment of Medical and Surgical Sciences and Advanced Technology G.F. Ingrassia, University of Catania, Via Santa Sofia 86, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyIRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyLiver fibrosis is defined as excessive extracellular matrix deposition in the hepatic parenchyma as a consequence of complex interactions among matrix-producing hepatic stellate cells (HSCs) and liver-resident and infiltrating cells. In addition to the liver, the process of fibrosis may represent end-stage disease of several diseases including kidneys, lungs, spleens, heart, muscles and at certain extent, the central nervous system and the peripheral nerves. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development. The aim of the present study was to test the efficacy of a new drug combination for the treatment of hepatic fibrosis in order to provide a proof-of-concept for the use of therapeutic agents in clinical practice. For this purpose, we have studied the effects of the PDGF inhibitor imatinib and the angiogenesis inhibitor sorafenib, administered alone or in combination, in reducing the progression of the fibrogenetic process in a pre-clinical model of liver damage induced in mice by repeated administration of Concanavalin A (ConA), resembling long-tern autoimmune hepatitis. Our results suggest that treatments with imatinib and sorafenib can modulate potently and, in a superimposable fashion, the fibrinogenic process when administered alone. However, and in agreement with the computational data presently generated, they only exert partial overlapping antifibrotic effects in modulating the main pathways involved in the process of liver fibrosis, without significant additive or synergist effects, when administered in combination.https://www.mdpi.com/1420-3049/25/18/4310liver fibrosisimatinibsorafenibtraumatic spinal cord injury |
| spellingShingle | Antonio Pesce Rosella Ciurleo Alessia Bramanti Eliana Concetta Armeli Iapichino Maria Cristina Petralia Gaetano Giuseppe Magro Paolo Fagone Placido Bramanti Ferdinando Nicoletti Katia Mangano Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis Molecules liver fibrosis imatinib sorafenib traumatic spinal cord injury |
| title | Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis |
| title_full | Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis |
| title_fullStr | Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis |
| title_full_unstemmed | Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis |
| title_short | Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis |
| title_sort | effects of combined admistration of imatinib and sorafenib in a murine model of liver fibrosis |
| topic | liver fibrosis imatinib sorafenib traumatic spinal cord injury |
| url | https://www.mdpi.com/1420-3049/25/18/4310 |
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