Ichi Ikuyo, Nakahara Kayoko, Fujii Kozue, Iida Chinatsu, Miyashita Yayoi, Kojo Shosuke
Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
J Nutr Sci Vitaminol (Tokyo). 2007 Feb;53(1):53-6. doi: 10.3177/jnsv.53.53.
In fulminant hepatic failure, various toxins causing multi-organ failure increase in plasma. As a novel toxin, levels of ceramide, a well-studied lipid mediator of apoptosis, were determined by LC-MS/MS in the liver and plasma of carbon tetrachloride (CCl4)-intoxicated rats. After 6 h of oral administration of CCl4 (4 mL/kg body weight as a 1:1 mixture of CCl4 and mineral oil) to rats, extensive hepatic failure occurred as evidenced by a severe elevation in plasma AST and ALT. The liver concentration of major ceramide components (C16:0, C24:0, C24:1, C18:0, C22:0, and C24:2 in decreasing order), and the sum of these ceramides increased significantly 2 h after CCl4 intoxication compared to that in the control group given mineral oil. The total ceramide concentration in the plasma was also increased to 4.1 times that in the control 24 h after administration of CCl4. In conclusion, the early increase in liver ceramides may contribute to hepatic cell death and the increase in plasma ceramides during fulminant hepatic failure may cause damage in other organs including the brain and kidney.
在暴发性肝衰竭中，导致多器官功能衰竭的各种毒素在血浆中增加。作为一种新型毒素，通过液相色谱 - 串联质谱法（LC-MS/MS）测定了四氯化碳（CCl4）中毒大鼠肝脏和血浆中神经酰胺（一种研究充分的凋亡脂质介质）的水平。给大鼠口服CCl4（4 mL/kg体重，以CCl4与矿物油1:1的混合物形式）6小时后，血浆天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）严重升高，表明发生了广泛的肝衰竭。与给予矿物油的对照组相比，CCl4中毒2小时后，主要神经酰胺成分（按降序排列为C16:0、C24:0、C24:1、C18:0、C22:0和C24:2）的肝脏浓度以及这些神经酰胺的总和显著增加。给予CCl4 24小时后，血浆中的总神经酰胺浓度也增加到对照组的4.1倍。总之，肝脏神经酰胺的早期增加可能导致肝细胞死亡，暴发性肝衰竭期间血浆神经酰胺的增加可能会对包括脑和肾在内的其他器官造成损害。
