Effect of α-tocopherol on carbon tetrachloride intoxication in the rat liver

Carbon tetrachloride (1 ml/kg body weight as a 1:1 mixture of CCl4 and mineral oil) was orally administered to rats. After 12 h, the activity of plasma ALT (alanine aminotransferase) was significantly higher than that of the control group, and plasma ALT and AST (aspartate aminotransferase) activities significantly increased 24 h after CCl4 administration. These results indicated that the necrotic process had initiated at about 12 h and developed thereafter. After 6-24 h of CCl4 administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced 6 h after CCl4 intoxication and thereafter. Oral administration of vitamin E (1 ml/kg body weight as a 1:1 mixture of alpha-tocopherol and mineral oil) 12 h before CCl4 administration caused a significant elevation of liver vitamin E level and ameliorated liver necrosis 24 h after CCl4 intoxication based on plasma AST and ALT. Vitamin E also significantly restored the hepatic vitamin C concentration 12 and 24 h after CCl4 intoxication, demonstrating that vitamin E functioned as an antioxidant. The liver vitamin E concentration was not changed by vitamin E supplementation to rats that did not receive CCl4. This result indicated that vitamin E accumulated in the damaged liver. The activation of JNK, ERK1/2 and p38 MAPK took place 1.5 h after CCl4 administration. Co-administration of alpha-tocopherol with CCl4 did not affect these early changes in MAPKs.