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