Activation of mitogen activated protein kinase (MAPK) during carbon tetrachloride intoxication in the rat liver

Carbon tetrachloride (CCl4: 4 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 AST (aspartate aminotransferase) and ALT (alanine aminotransferase) was significantly higher than that of the control group and plasma AST and ALT activities increased thereafter. These results indicated that the necrotic process was active at about 12 h and developed thereafter. After 2-24 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 as early as 2 h after CCl4 intoxication and thereafter. Phosphorylated JNK (c-Jun NH2-terminal kinase) and phospho-ERK1/2 (extracellular signal-regulated kinase1/2) were significantly increased transiently 1-3 h after treatment with CCl4, while phosphorylated p38 decreased significantly 1-24 h after CCl4 treatment. These results indicated that the change in MAPKs (mitogen activated protein kinases) slightly preceded that in vitamin C, the most sensitive chemical indicator of oxidative stress.