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

Abstract

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 (25mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5-10μg) was administered 30min 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 8h after the ConA injection. RESULTS Following ConA challenge, the expression of cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-α, IL-1β 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.

DOI: 10.1016/j.biopha.2016.03.012

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@article{Chen201615dPGJ2AC, title={15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy.}, author={Kan Chen and Jingjing Li and Sainan Li and Jiao Feng and Liwei Wu and Tong Liu and Rong Zhang and Shizan Xu and Keran Cheng and Yuqing Zhou and Shunfeng Zhou and Fan Wang and Weiqi Dai and Yujing Xia and Jie Lu and Yingqun Zhou and Chuanyong Guo}, journal={Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, year={2016}, volume={80}, pages={183-92} }