Increase of ceramide in the liver and plasma after carbon tetrachloride intoxication in the rat.

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.