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载槲皮素壳聚糖/海藻酸钠颗粒在对乙酰氨基酚诱导的毒性模型中的体内外肝保护和抗氧化活性。

Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity.

机构信息

Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.

Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.

出版信息

Biomed Pharmacother. 2017 Aug;92:569-579. doi: 10.1016/j.biopha.2017.05.008.

Abstract

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus, quercetin was encapsulated in chitosan/alginate nanoparticles by gelation method. Both empty and quercetin-loaded nanoparticles revealed good safety profile in vitro, determined by the lack of cytotoxicity in human hepatoma HepG2 cells. The pretreatment of HepG2 cells with encapsulated quercetin (10μg/ml) significantly attenuated the decrease in cell viability in HО-induced oxidative stress (0.1mM HО) thus showing an effective in vitro protection. In vivo evaluation of the antioxidant and hepatoprotective potential of free and encapsulated quercetin was performed in a model of paracetamol - induced liver injury in male Wistar rats. The oral pretreatment with encapsulated quercetin (0.18mg/kg b.w., 7days) significantly diminished the increased levels of serum transaminases ALT and AST, attenuated the lipid peroxidation and restored the levels of gluthation (a marker of cell antioxidant defence system). The protective effects of quercetin encapsulated in chitosan-based nanoformulation were superior to those of free quercetin. The results of the study suggest that the encapsulation of quercetin in chitosan/alginate nanoformulations might represent an effective therapeutic approach against oxidative stress induced liver injury.

摘要

自由基损伤或过量活性氧(ROS)形成引起的毒性肝损伤可以通过天然抗氧化剂有效减轻。本研究旨在探索和比较游离态和包封态槲皮素在体外和体内肝毒性模型中的保肝和抗氧化作用。因此,采用凝胶化法将槲皮素包封于壳聚糖/海藻酸钠纳米粒子中。通过体外实验,确定了游离态和包封态纳米粒子均无细胞毒性,表现出良好的安全性。用包封态槲皮素(10μg/ml)预处理 HepG2 细胞,可显著减轻 H0 诱导的氧化应激(0.1mM H0)引起的细胞活力下降,从而表现出有效的体外保护作用。采用对乙酰氨基酚诱导的雄性 Wistar 大鼠肝损伤模型,对游离态和包封态槲皮素的抗氧化和保肝作用进行了体内评价。壳聚糖基纳米制剂包封态槲皮素(0.18mg/kg b.w.,7 天)的口服预处理可显著降低血清转氨酶 ALT 和 AST 的升高水平,减轻脂质过氧化作用,并恢复谷胱甘肽(细胞抗氧化防御系统的标志物)的水平。壳聚糖/海藻酸钠纳米制剂包封态槲皮素的保护作用优于游离态槲皮素。研究结果表明,壳聚糖/海藻酸钠纳米制剂包封槲皮素可能是一种针对氧化应激诱导肝损伤的有效治疗方法。

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