Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E.
Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E.
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含维生素E的脂质体抑制四氯化碳引起的肝损伤。
DOI：
10.1152/ajpgi.1994.267.3.g476
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Zern,MA
中科院分区：
文献类型：
--
作者：
Yao,T;DegliEsposti,S;Huang,L;Arnon,R;Spangenberger,A;Zern,MA
我们测试了各种抗氧化剂作为可能的治疗药物在急性四氯化碳肝毒性小鼠模型。肝损伤，测量的血清转氨酶释放到血液中的量，形态学变化，致死剂量反应，和硫代巴比妥酸反应物质（TBARS）的存在下，显着抑制剂量依赖性的方式由脂质体含有维生素E（LVE）或Rocavit E，α-生育酚的水溶性乳剂。LVE或Rocavit E处理动物的血清转氨酶水平始终比相应的CCl 4对照组低10倍以上。其他脂质体相关的抗氧化剂，丁基化羟基甲苯，维生素E琥珀酸酯，过氧化氢酶，去铁胺，超氧化物歧化酶和抗坏血酸6-棕榈酸酯，也能够引起损害的减少，但是，它们的有效性大大降低。当给予致死剂量的CCl 4时，静脉注射LVE可使死亡率降低近90%。当检查脂质体的生物分布时，确定绝大多数位于枯否细胞群中。这种将无毒治疗剂选择性地递送至肝脏的方法在人类中提供了多种临床应用。
We tested a variety of antioxidants as possible therapeutic agents in an acute CCl4 mouse model of hepatotoxicity. Liver damage, gauged by the amount of serum aminotransferase released into the blood, morphological changes, lethal dose response, and presence of thiobarbituric acid-reactive substances (TBARS), were significantly inhibited in a dose-dependent manner by liposomes containing vitamin E (LVE) or by Rocavit E, a water-soluble emulsion of alpha-tocopherol. Serum aminotransferase levels in LVE- or Rocavit E-treated animals were always > 10-fold lower than levels in corresponding CCl4 controls. Other liposome-associated antioxidants, butylated hydroxytoluene, vitamin E succinate, catalase, desferoxamine, superoxide dismutase, and ascorbic acid 6-palmitate, were also able to elicit a decrease in damage; however, they were substantially less effective. Intravenous therapy with LVE decreased mortality by nearly 90% when a lethal dose of CCl4 was given. When the biodistribution of the liposomes was examined, it was determined that the vast majority were localized in the Kupffer cell population. This approach of delivering nontoxic therapeutic agents selectively to the liver offers a variety of clinical applications in humans.