Role of C-Jun N terminal kinase (JNK) signaling pathway in acetaminophen hepatotoxicity

Acetaminophen (APAP) is a commonly used analgesics and antipyretic agent. The therapeutic or recommended dose of APAP is not associated with adverse effects. However, intentional or unintentional overdose of APAP causes acute liver injury or acute liver failure if treatment is delayed. Currently, APAP-induced liver injury is one of the major causes of acute liver injury in the United States and other western countries. C-Jun N terminal kinase (JNK) implicated in stress-related signaling pathway plays an indispensable role in the mechanism of APAP hepatotoxicity. JNK mediates depletion of mitochondrial glutathione in the metabolic phase and enhances oxidative stress to aggravate liver injury. In addition, JNK plays an important role in APAP-induced apoptosis, necrosis or other forms of cell death. Furthermore, JNK plays a role in regulation of endogenous immune system and aseptic inflammatory responses induced by APAP. However, JNK may promote cell regeneration after APAP-induced cell death. The present review therefore highlights the functions of JNK in APAP-induced liver injury.