ABSTRACT

Recently, the fundamental roles of microRNAs (miRNAs) in the progression and development of diseases have been shown in several studies. In the liver 70% of all expressed miRNAs is miR-122; therefore it is measured as a liver-specific miRNA. The aim of this work was to evaluate the hepatoprotective and radioprotective effect of orally administrated naringin and silymarin pre-treatment in CCl4-intoxicated and γ-irradiated rats, also to study the change of gene expression of microRNA and change of IL-6 levels to find powerful and reliable tools that can be used as a biomarker for the diagnosis of hepatotoxicity and radiation exposure for monitoring and treatment. This study revealed that pre-treatment of rats with naringin orally (80 mg/kg b,w) significantly restored the levels of superoxide dismutase (SOD), lipid peroxidation (MDA) and reduced glutathione (GSH) in rats injected with 1 ml/kg b.wi.p CCl4 and in rats exposed to 7 Gray single one shot dose of γ radiations. The combination between naringin and silymarin resulted in significant reduction in IL-6 level in hepatotoxic rats. MicroRNA-122 expression changes in hepatotoxicity and radiation emphasize the great value of miRNA signatures as hepatotoxicity and radiation biomarker.

摘要

近来，在若干研究中已经显示了微小RNA（miRNA）在疾病的进展和发展中的基本作用。在肝脏中，所有表达的miRNA的70％是miR-122；因此，它被测量为肝脏特异性的miRNA。这项工作的目的是评估经口服柚皮苷和水飞蓟素预处理对CCl4中毒和γ射线照射的大鼠的肝保护和放射防护作用，并研究microRNA的基因表达变化和IL-6水平对找到功能强大且可靠的工具，可以将其用作诊断肝毒性和辐射暴露的生物标志物，以进行监测和治疗。这项研究表明，口服柚皮苷（80 mg / kg b，w）预处理的大鼠可显着恢复超氧化物歧化酶（SOD）的水平，注射1 ml / kg b.wi.p CCl4的大鼠和暴露于7 Gray单次单剂量γ辐射的大鼠体内脂质过氧化（MDA）和还原型谷胱甘肽（GSH）含量。柚皮苷和水飞蓟素的组合导致肝毒性大鼠的IL-6水平显着降低。MicroRNA-122在肝毒性和放射中的表达变化强调了miRNA标记物作为肝毒性和放射生物标志物的巨大价值。