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首页> 外文期刊>Current therapeutic research, clinical and experimental. >Protective Effect of FTY720 on Several Markers of Liver Injury Induced by Concanavalin A in Mice
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Protective Effect of FTY720 on Several Markers of Liver Injury Induced by Concanavalin A in Mice

机译：FTY720对伴刀豆球蛋白A致小鼠肝损伤的几种标志物的保护作用

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摘要

BACKGROUND: 2-Amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diol hydro-chloride (FTY720) is a novel agent with protective effect on several markers of liver injury. It is a chemical substance derived by modifying myriocin from the ascomycete Isaria sinclairii. It has been reported that FTY720 is able to treat autoimmune encephalomyelitis, renal cancer, asthma, and multiple sclerosis. More potent clinical applications of FTY720 need to be investigated.Objective: The aim of this study was to evaluate the protective effect of FTY720 on several markers of experimental liver injury and to investigate the possible mechanism of action.METHODS: Concanavalin A (Con A) at a dose of 15 mg/kg was intravenously, injected in mice, and 10 days before the Con A challenge, 1 mg/kg, 3 mg/kg, and 6 mg/kg of FTY720 were administered to mice. The liver injury was monitored biochemically by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNF-a) levels. TNF-a and nuclear factor-kappaB (NF-kappaB) in liver tissue were detected by Western blot analysis.RESULTS: FTY720, when administered intragastrically for 10 days in mice with Con A-induced liver injury, dose-dependently reduced serum ALT and AST and TNF-a levels. The differences were statistically significant (P <= 0.05). It was also found that FTY720 decreases TNF-alpha and NF-kappaB protein expression in liver tissue.CONCLUSIONS: FTY720 is able to improve several markers of Con A—induced liver injury in mice, including serum ALT, serum AST, TNF-alpha, and NF-kappaB, which might be at least in part related to its ability to reduce TNF-alpha/NF-kappaB cascade activity.
机译：背景：2-氨基-2- [2-（4-辛基苯基）乙基]丙烷-1,3-二醇盐酸盐（FTY720）是一种对多种肝损伤标志物具有保护作用的新型药物。它是通过修饰子囊鼠尾草Isaria incinclairii中的myriocin衍生而来的化学物质。据报道，FTY720能够治疗自身免疫性脑脊髓炎，肾癌，哮喘和多发性硬化症。 FTY720在临床上有更广泛的应用前景。目的：本研究旨在评估FTY720对几种实验性肝损伤标志物的保护作用，并探讨其可能的作用机理。方法：伴刀豆球蛋白A（Con A）以15 mg / kg的剂量静脉内注射，并在小鼠中注射，在Con A攻击前10天，向小鼠施用1 mg / kg，3 mg / kg和6 mg / kg的FTY720。通过测量血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）和肿瘤坏死因子-α（TNF-a）的水平来生化监测肝损伤。结果：FTY720在Con A诱导的肝损伤小鼠中经胃内给药10天后，剂量依赖性地降低了血清ALT和TNF-α水平，从而降低了肝组织中TNF-α和NF-κB的表达。 AST和TNF-α水平。差异具有统计学意义（P <= 0.05）。还发现FTY720降低了肝组织中TNF-α和NF-κB蛋白的表达。结论：FTY720能够改善Con A诱发的小鼠肝损伤的几种标志物，包括血清ALT，血清AST，TNF-α，和NF-κB，这可能至少部分与其降低TNF-α/NF-κB级联活性的能力有关。

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