Activation of mitogen activated protein kinase (MAPK) during d-galactosamine intoxication in the rat liver

A significant increase in plasma glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase was observed 6 h after intraperitoneal administration of d-galactosamine (d-Galn). Three hours after administration of d-Galn, the vitamin C concentration in the liver decreased significantly compared to that in a control group and thereafter the hepatic vitamin C concentration remained at a significantly lower level. Phosphorylated JNK (c-Jun NH2-terminal kinase) and phosphorylated ERK (extracellular signal-regulated kinase) started increasing 3 h after d-Galn treatment and remained at a high level for 6–12 h after the treatment, while phosphorylated p38 MAPK increased significantly 6 h after d-Galn administration. These results indicated that oxidative stress and the activation of JNK and ERK took place almost simultaneously, followed by the activation of p38 MAPK.