Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis
| Autor: | Maria Cristina Petralia, Gaetano Magro, Katia Mangano, Alessia Bramanti, Rosella Ciurleo, Placido Bramanti, Paolo Fagone, Eliana Concetta Armeli Iapichino, Antonio Pesce, Ferdinando Nicoletti |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Liver Cirrhosis
Pharmaceutical Science Angiogenesis Inhibitors Autoimmune hepatitis Pharmacology Analytical Chemistry Mice 0302 clinical medicine Fibrosis Receptors Drug Discovery Concanavalin A Receptors Platelet-Derived Growth Factor Traumatic spinal cord injury Inbred BALB C Platelet-Derived Growth Factor Mice Inbred BALB C 0303 health sciences biology Drug Synergism Sorafenib Angiogenesis inhibitor Liver Chemistry (miscellaneous) 030220 oncology & carcinogenesis Combination Imatinib Mesylate Molecular Medicine Drug Therapy Combination Female Platelet-derived growth factor receptor medicine.drug Liver fibrosis Article lcsh:QD241-441 03 medical and health sciences lcsh:Organic chemistry Drug Therapy Hepatic Stellate Cells medicine Animals Humans Computer Simulation Physical and Theoretical Chemistry Protein Kinase Inhibitors 030304 developmental biology Animal business.industry Organic Chemistry Imatinib medicine.disease Disease Models Animal Disease Models biology.protein Hepatic stellate cell Hepatic fibrosis business |
| Zdroj: | Molecules Volume 25 Issue 18 Molecules, Vol 25, Iss 4310, p 4310 (2020) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules25184310 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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