Prevention of acetaminophen-induced hepatocyte injury: JNK inhibition and GSTA1 involvement

Abstract

Glutathione S-transferase A1 (GSTA1) is a detoxification enzyme and a sensitive marker for hepatotoxicity. We investigated the effects of JNK inhibition on different degrees of Acetaminophen (APAP)-induced hepatocyte injury and GSTA1 expression. This study aimed to investigate the role of JNK signaling pathway in APAP-induced different degrees of hepatocyte injury and its correlation with GSTA1 by inhibiting the phosphorylation of JNK by SP600125. 6 and 8\xa0mM APAP induced different degrees of hepatocyte injury and apoptosis, both activated JNK signaling pathway. In contrast, JNK inhibitor significantly reduced activation of JNK and c-JUN on exposure to APAP. Meanwhile, the levels of hepatocyte injury, oxidative stress, and apoptosis obviously decreased. Importantly, GSTA1 expression was significantly increased by JNK inhibition. JNK inhibition attenuates APAP-induced hepatocyte injury and oxidative stress and increases GSTA1 expression. Furthermore, GSTA1 may be involved in this signaling pathway for detoxification.