15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy

Objective: In this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism. Materials and methods: Balb/C mice were injected with ConA (25 mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5-10 mu g) was administered 30 min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8 h after the ConA injection. Results: Following ConA challenge, the expression of cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-alpha, IL-1 beta and ROS after injection. 15d-PGJ2 inhibited apoptosis and autophagic cell death, facilitated Nrf2 nuclear translocation, increased HO-1 expression and suppressed the JNK activation. Conclusion: 15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating the anti-oxidative stress factor HO-1 and reducing the production of cytokines and ROS, thereby inhibiting hepatic cell autophagy probably induced by ROS. (C) 2016 Elsevier Masson SAS. All rights reserved.