蓝点马鲛鱼皮抗氧化肽FractionⅡ对D-Gal诱导氧化损伤大鼠肝脏的保护作用

研究蓝点马鲛鱼皮抗氧化肽FractionⅡ(1~4 ku)对氧化损伤Wistar大鼠肝脏的保护作用。采用D-半乳糖(D-gal)建立衰老模型,实验大鼠随机分为6组:空白对照组;D-Gal模型阴性对照组;D-Gal+维生素E(VE)阳性对照组;抗氧化肽低、中、高剂量组。通过检测血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)和单胺氧化酶(MAO)活性及肝组织匀浆液中超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性,丙二醛(MDA)、一氧化氮(NO)含量和总抗氧化能力(T-AOC),并结合组织形态学来评价FractionⅡ对氧化损伤肝脏的作用效果。结果显示,与阴性对照相比,各剂量组的FractionⅡ能够显著降低大鼠血清中的AST和ALT活性,提高肝脏组织的SOD、GSH-Px、CAT活性和T-AOC能力,降低MDA和NO含量及MAO水平,并成一定的量效依赖关系。其中效果较好的高剂量(200 mg/kg)多肽处理组SOD、GSH-Px活性分别为236.27、182.23 U/mg蛋白,达到了正常对照及阳性对照组水平;AST、ALT分别降低至302.47和220.43 U/L,MDA含量降低至138.83 nmol/mg蛋白,也达到正常对照组水平。H.E.染色结果也证实,FractionⅡ在保护肝细胞完整性、维持结构清晰、抑制坏死等方面都有一定的效果。研究表明,蓝点马鲛鱼皮抗氧化肽FractionⅡ对D-Gal诱导的氧化损伤大鼠肝脏具有较好的保护作用。

Protective effects of Spanish mackerel (Scomberomorous niphonius) skin peptides against D-Gal-induced liver damage in rats

Epidemiological studies consistently show that excessive amounts of reactive oxygen species (ROS) is an important underlying cause of the initiation of oxidative stress in various tissue injuries as well as cell death and several chronic diseases. Several compounds, such as D-Galactose (D-Gal), bromobenzene, carbon tetrachloride (CCl4), acetaminophen, and ethanol have been implicated in the etiology of liver diseases. D-Gal is commonly used as a toxin to induce reactive oxygen species and hepatic disorders, which has been extensively used in oxidative damage animal models to evaluate the therapeutic potential of drugs and dietary antioxidants. Due to the risks of synthetic antioxidants, there is a growing interest in the use of natural antioxidants to prevent ROS related liver pathologies. Therefore, during the past several decades, human nutrition and biochemistry research focused on antioxidants derived from foods that could prevent or diminish ROS-induced damage. More recently, there is growing interest in natural hydrolysed protein antioxidants from many plant and animal sources. So, we hypothesized that the administration of antioxidant peptides might be useful for preventing various types of oxidative stress in vivo. In our previous experimental studies, Fraction Ⅰ (MW <1 ku), Fraction Ⅱ (MW 1–4 ku) and Fraction Ⅲ (MW >4 ku) were isolated from the hydrolysates ofScomberomorous niphonius skin through ultrafiltration membrane with the cutoff of 1 and 4 ku, respectively. Among them, the Fraction (1–4 ku) exhibited the highest radical scavenging activity, inhibiting both lipid and protein oxidation of cooked patties during refrigerated storage, and protecting Caco-2 cells against the toxicity caused by H2O2. Therefore, the aim of this study was to evaluate the antioxidant effects of Fraction Ⅱ on D-Gal-induced liver damage in rats. Wistar rats were randomly divided into 6 groups, which were normal control, negative control, D-Gal+Low-dose of Fraction Ⅱ, D-Gal+Middle-dose of Fraction Ⅱ, D-Gal+High-dose of Fraction Ⅱ, and D-Gal +VE as positive control for seven weeks. The activities of serum asparate aminotransferase (AST), alanine aminotransferase (ALT), monoamine oxidase (MAO) and antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), nitric oxide (NO) and malondialdehyde (MDA) contents in liver were determined. The result showed that all doses of Fraction Ⅱ could significantly reduce the ALT and AST level in serum of the rat, while M-dose and H-dose of Fraction could sharply decrease the MAO level. Compared with negative control group, SOD, GSH-Px, CAT activity and T-AOC of liver of the rats were increased significantly. the MDA and NO contents in liver of the rats were reduced when treated with all doses of Fraction. Treatment with high dose Fraction (200 mg/kg) could increase the SOD, GSH-Px activity to 236.27 and 182.23 U/mg protein, which could reach the level of normal and positive control, decrease the contents of AST, ALT and MDA to 302.47 U/L, 220.43 U/L and 138.83 nmol/mg protein, which was close to the level of normal control. Moreover, Fraction Ⅱ could significantly reduce the injury score of prominent nucleus, visible central veins and necrosis in rats. These data indicate that Fraction Ⅱ can protect the liver against D-Gal induced oxidative damage.