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Effects of Vitamin C and Melatonin on Cysteamine-Induced Duodenal Ulcer in a Cholestatic Rat Model: A Controlled Experimental Study

机译:维生素C和褪黑激素对胆汁淤积大鼠模型中半胱胺诱导的十二指肠溃疡的影响:对照实验研究

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BACKGROUND: Superoxide dismutase (SOD) is one of the defense mechanisms against free radicals. Cysteamine is a cytotoxic agent, acting through generation of reactive oxygen species (ROS) such as hydrogen peroxide, hydroxyl radical, and super-oxide, and may decrease defense activity of SOD against ROS and induce duodenal ulcer. Melatonin is a suicidal antioxidant that has a protective effect against ROS and cytoprotective effect through inhibition of the decrease in SOD activity. OBJECTIVES: The primary aim of this study was to assess the effects of pretreat-ment with vitamin C and melatonin on cysteamine-induced duodenal ulcer. Secondary aims were to compare the ulcerogenic effect of cysteamine and the antiulcer effects of vitamin C and melatonin. METHODS: This study was performed in male Wistar rats (200-250 g) in 3 groups of equal size (n = 24): bile duct ligation-induced cholestasis (test), sham, and control groups. In the test and sham groups, laparotomy was performed under general anesthesia and the common bile duct was identified; in sham rats, the common bile duct was left in situ, but in test rats, the common bile duct was isolated and doubly ligated to induce cholestasis. Animals in each group were also divided into 4 equal subgroups (n = 6). These subgroups were treated with vitamin C plus cysteamine, melatonin plus cysteamine, cysteamine alone, and saline, respectively. All animals were euthanized via overdose of ether anesthesia 24 hours after the last injection of cysteamine or saline, and 0.5 mL of blood was collected from the heart ventricle. The duodenum was cut open, washed with saline, fixed, and prepared for calculation of ulcer index (Szabo method) and histopathologic assessment. SOD activity was measured using a branded enzyme kit. RESULTS: In all 3 groups, animals treated with cysteamine had significantly increased mean (SE) ulcer index (test, 4.00 [0.10] vs 1.17 [0.30]; sham, 3.83 [0.16] vs 0.50 [0.22]; control, 3.67 [0.21] vs 0 [0]) and de...
机译:背景:超氧化物歧化酶(SOD)是防御自由基的防御机制之一。半胱胺是一种细胞毒剂,通过生成过氧化氢,羟基自由基和超氧化物等活性氧(ROS)起作用,并可能降低SOD对ROS的防御活性并诱发十二指肠溃疡。褪黑激素是一种自杀性抗氧化剂,通过抑制SOD活性的下降而具有针对ROS的保护作用和细胞保护作用。目的:本研究的主要目的是评估维生素C和褪黑素预处理对半胱胺诱发的十二指肠溃疡的影响。次要目的是比较半胱胺的致溃疡作用以及维生素C和褪黑激素的抗溃疡作用。方法:本研究在200只至250 g的雄性Wistar大鼠中分为3组,每组相等大小(n = 24):胆管结扎诱发的胆汁淤积(试验),假手术和对照组。在试验组和假手术组中,在全身麻醉下进行剖腹手术,并确定胆总管。在假手术大鼠中,胆总管留在原处,而在实验大鼠中,胆总管被分离并双重结扎以诱发胆汁淤积。每组中的动物也分为四个相等的亚组(n = 6)。这些亚组分别用维生素C加半胱胺,褪黑素加半胱胺,单独的半胱胺和盐水治疗。最后一次注射半胱胺或盐水后24小时,通过过量的乙醚麻醉使所有动物安乐死,并从心脏心室收集0.5 mL血液。将十二指肠切开,用盐水洗涤,固定,并准备用于计算溃疡指数(Szabo法)和组织病理学评估。使用商标酶试剂盒测量SOD活性。结果:在所有3组中,用半胱胺治疗的动物的平均(SE)溃疡指数均显着增加(测试,4.00 [0.10]对1.17 [0.30];假手术,3.83 [0.16]对0.50 [0.22];对照组,3.67 [0.21] ] vs 0 [0])并删除...

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