15-deoxyprostaglandin-j2 and Hepatitis

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.. 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.. 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.. 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.

Topics: Acute Disease; Animals; Autophagy; Cell Nucleus; Concanavalin A; Disease Models, Animal; Enzyme Activation; Heme Oxygenase-1; Hepatitis; Hepatocytes; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Liver; Male; Mice, Inbred BALB C; NF-E2-Related Factor 2; Phagosomes; Prostaglandin D2; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Up-Regulation