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首页> 外文期刊>Toxicology and Applied Pharmacology >Protection from spontaneous hepatocellular damage by N-benzyl-d-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease.
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Protection from spontaneous hepatocellular damage by N-benzyl-d-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease.

机译:N-苄基-d-葡糖胺二硫代氨基甲酸酯对威尔森氏病动物模型Long-Evans肉桂大鼠的自发性肝细胞损伤的保护作用。

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The Long-Evans Cinnamon (LEC) rat is a mutant strain that accumulates excessive tissue copper (Cu) and models the clinical symptoms and biological features of Wilson's disease in humans. We compared the effects of three metal chelating agents, N-benzyl-d-glucamine dithiocarbamate (BGD), d-penicillamine (D-PEN), and triethylenetetramine (TETA), on the biliary and urinary excretions of Cu using LEC rats. The animals were treated ip with each chelating agent (1 mmol/kg body weight) and then the bile and urine samples were collected for 3 h. Because single treatment with BGD markedly stimulated biliary excretion of Cu, the protective effect of repeated BGD injection on spontaneous hepatocellular damage was further examined. Separate groups received two weekly injections of BGD starting at 11 weeks of age and were compared to saline-injected controls. Serum alanine aminotransferase (ALT) activity and bilirubin level were significantly increased in control LEC rats by 19 weeks of age and histopathological analysis demonstrated extensive hepatic damage in these rats. However, repeated BGD injections prevented the increases in serum ALT and bilirubin and blocked the histopathological changes in the liver. Furthermore, although Cu rapidly accumulated in the liver, kidney, spleen, and serum of control LEC rats during the test period, repeated BGD injection largely prevented these increases. These results indicate that BGD treatment is effective in blocking excessive Cu accumulation in LEC rats that, in turn, provides protection from spontaneous liver damage.
机译:Long-Evans Cinnamon(LEC)大鼠是一种突变株,可累积过多的组织铜(Cu),并模拟人类威尔逊氏病的临床症状和生物学特征。我们使用LEC大鼠比较了三种金属螯合剂N-苄基-d-葡糖胺二硫代氨基甲酸酯(BGD),d-青霉胺(D-PEN)和三亚乙基四胺(TETA)对铜的胆汁和尿液排泄的影响。用每种螯合剂(1 mmol / kg体重)腹膜内处理动物,然后收集胆汁和尿液样品3小时。因为用BGD单次治疗显着刺激了铜的胆汁排泄,所以进一步检查了重复BGD注射对自发性肝细胞损伤的保护作用。从11周龄开始,独立的组每周接受两次BGD注射,并与注射生理盐水的对照组进行比较。对照LEC大鼠到19周龄时,血清丙氨酸氨基转移酶(ALT)活性和胆红素水平显着增加,并且组织病理学分析表明这些大鼠有广泛的肝损伤。但是,反复注射BGD可以防止血清ALT和胆红素升高,并阻止肝脏的组织病理学改变。此外,尽管在测试期间Cu在对照LEC大鼠的肝脏,肾脏,脾脏和血清中迅速积累,但是重复BGD注射在很大程度上阻止了这些增加。这些结果表明,BGD治疗可有效阻止LEC大鼠中过量的Cu积聚,进而提供保护,使其免受自然肝损害。

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