科研之友
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摘要
Objectives: Dasatinib, a potent and broad-spectrum tyrosine kinase inhibitor, is approved for the treatment of imatinib-resistant chronic myelogenous leukemia. The aim of this study was to evaluate the anti-fibrotic, anti-inflammatory and antioxidant effects of this agent against CCl4-induced hepatic fibrosis and oxidative status. Materials and methods: Experimental fibrosis was induced in Wistar male rats by 12 weeks of CCl4 administration (i.p.). During the last 8 weeks of injection, rats were gavaged daily with Dasatinib (10 mg/kg). To evaluate anti-inflammatory and anti-fibrotic effects of Dasatinib, histopathological examination of liver tissue was performed and serum ALT and AST activities, oxidant, antioxidant parameters and hepatic tumor necrosis factor alpha (TNF-alpha) were examined. Moreover, transforming growth factor (TGF-beta(1)), platelet derived growth factor (PDGF) and TNF-alpha mRNA expressions were also evaluated by real time polymerase chain reaction. Results: Dasatinib administration induced a significant reduction of ALT and AST activities (p<.001) and Malondialdehyde (MDA) content in CCl4 injected rats (p<.05). Concomitantly hepatic protein and mRNA expression of TNF-alpha, mRNA expression of TGF-beta(1) and PDGF were increased due to CCl4 intoxication (p<.001), but Dasatinib treatment could significantly ameliorate these mediators at the level of gene expression (p<.01) and protein level of TNF-alpha (p<.001). The necro-inflammatory changes in histopathological finding, nitric oxide and hydroxyproline level were also increased during 12 weeks of CCl4 administration which was significantly attenuated by Dasatinib (p<.01). Discussion and conclusion: Our findings indicate that Dasatinib can be cautiously an anti-fibrotic, anti-inflammatory and anti-oxidative agent in clinical setting.
- 出版日期2017-2
