Change in liver and plasma ceramides during D-galactosamine-induced acute hepatic injury by LC-MS/MS

Change in liver and plasma ceramides during D-galactosamine-induced acute hepatic injury by LC-MS/MS
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DOI:
10.1016/j.bmcl.2004.05.046
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发表时间:
2004-08-02
影响因子:
2.7
通讯作者:
Kojo, S
Kojo, S
中科院分区:
医学4区
文献类型:
--
作者:
Yamaguchi, M;Miyashita, Y;Kojo, S

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在暴发性肝衰竭中,血浆中引起多器官衰竭的各种毒素增加。作为一种新的毒素,神经酰胺,一个良好的研究脂质介导的细胞凋亡,水平测定LC-MS/MS在D-半乳糖胺中毒大鼠的肝脏和血浆。大鼠腹腔注射D-半乳糖胺(1 g/kg体重)后18和24 h,血浆GOT和GPT严重升高,证明发生了暴发性肝衰竭。与给予生理盐水的对照组相比,次要神经酰胺组分(C18:0、C20:0、C22:1、C22:0和C24:2)的肝脏浓度显著增加。D-半乳糖胺给药后24 h,主要神经酰胺(C24:0、C24:1、C16:0、C22:0、C22:1和C18:0)的血浆浓度增加,总神经酰胺浓度也增加至对照组的3.6倍。结论:暴发性肝功能衰竭时血浆中神经酰胺浓度升高可能是引起其他器官(包括脑和肾)损害的重要毒素之一。(C)2004 Elsevier Ltd.保留所有权利。
In fulminant hepatic failure, various toxins causing multi-organ failure increase in plasma. As a novel toxin, ceramide, a well-studied lipid mediator of apoptosis, levels were determined by LC-MS/MS in the liver and plasma of D-galactosamine-intoxicated rats. 18 and 24 h after intraperitoneal administration of D-galactosamine (1 g/kg body weight) to rats, fulminant hepatic failure occurred as evidenced by a severe elevation in plasma GOT and GPT. The liver concentration of minor ceramide components (C18:0, C20:0, C22:1, C22:0, and C24:2) increased significantly compared to that in the control group that was given saline. The plasma concentration of major ceramides (C24:0, C24:1, C16:0, C22:0, C22:1, and C18:0) increased 24h after administration of D-galactosamine and the total ceramide concentration was also increased to 3.6 times that in the control. In conclusion, the increased concentrations of ceramides in plasma during fulminant hepatic failure may be one of important toxins causing damage in other organs including the brain and kidney. (C) 2004 Elsevier Ltd. All rights reserved.