Khedr Naglaa F, Khedr Eman G
Faculty of Pharmacy, Tanta University, Postal number: 31527, Tanta, Egypt.
Fundam Clin Pharmacol. 2017 Oct;31(5):534-545. doi: 10.1111/fcp.12297. Epub 2017 Jul 19.
The alterations and low levels of circulating branched chain amino acids (BCAAs), leucine, isoleucine, and valine, are associated with liver diseases. The study was designed to evaluate hepatoprotective effect of BCAAs on CCl -induced liver fibrosis and to investigate the molecular mechanisms underlying these effects in rats. In all, 30 male rats were divided into three groups. Control group (n = 10) and CCl group (n = 10), where rats were injected with CCl (1 mL/kg of 0.5 : 1 v/v injected i.p. twice weekly for 12 weeks). In CCl + BCAAs group (n = 10), rats were injected with similar doses of CCl and supplemented with a mixture of 600 mg/kg BCAAs (2 : 1 : 1.2 leucine : isoleucine : valine) by oral gavage, three times/week for 12 weeks. Liver fibrosis was assessed by measuring total bilirubin, total protein, alanine aminotransferase, and aspartate aminotransferase, hydroxyproline content, and serum IL-6 and IL-10. Histopathologic studies and α-smooth muscle actin (α-SMA) were detected immunohistochemically in liver. Serum insulin level, blood glucose, liver malodialdehyde concentration (MDA), glutathione peroxidase, and superoxide dismutase (SOD) activities were quantified. TGF-β1, Smad3, and Smad7 gene expressions were estimated by qRT-PCR. BCAAs suppressed liver fibrosis induced by CCl treatment. BCAAs modulated liver indices and downregulated TGF-β1, Smad3, and Smad7 expressions in hepatocytes. BCAAs enhanced liver antioxidant enzyme activities (P < 0.001), reduced serum levels of TGF-β1, IL-6, and IL-10 compared to CCL group and ameliorated histopathologic changes in rat liver. BCAAs may have a protective role against liver fibrosis via antioxidant and anti-inflammatory mechanisms.
循环支链氨基酸（BCAAs）、亮氨酸、异亮氨酸和缬氨酸水平的改变及降低与肝脏疾病相关。本研究旨在评估BCAAs对四氯化碳（CCl）诱导的肝纤维化的肝保护作用，并探讨其在大鼠体内发挥这些作用的分子机制。总共30只雄性大鼠被分为三组。对照组（n = 10）和CCl组（n = 10），CCl组大鼠腹腔注射CCl（0.5:1 v/v，1 mL/kg，每周两次，共12周）。在CCl + BCAAs组（n = 10）中，大鼠注射相同剂量的CCl，并通过口服灌胃补充600 mg/kg的BCAAs混合物（亮氨酸:异亮氨酸:缬氨酸为2:1:1.2），每周三次，共12周。通过检测总胆红素、总蛋白、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、羟脯氨酸含量以及血清白细胞介素-6（IL-6）和白细胞介素-10（IL-10）来评估肝纤维化。采用免疫组织化学法检测肝脏的组织病理学研究和α-平滑肌肌动蛋白（α-SMA）。对血清胰岛素水平、血糖、肝脏丙二醛浓度（MDA）、谷胱甘肽过氧化物酶和超氧化物歧化酶（SOD）活性进行定量分析。通过实时定量聚合酶链反应（qRT-PCR）评估转化生长因子-β1（TGF-β1）、Smad3和Smad7基因表达。BCAAs抑制了CCl处理诱导的肝纤维化。BCAAs调节肝脏指标，并下调肝细胞中TGF-β1、Smad3和Smad7的表达。与CCl组相比，BCAAs增强了肝脏抗氧化酶活性（P < 0.001），降低了血清中TGF-β1、IL-6和IL-10的水平，并改善了大鼠肝脏的组织病理学变化。BCAAs可能通过抗氧化和抗炎机制对肝纤维化起到保护作用。
