Tissue injury and fibrosis was evaluated by standard techniques. Results: RyRs were expressed in macrophages with highest expression for RyR-1.Dantrolene

in culture reduced LPS-induced expression of pro-IL1 β and LPS+ATP-induced production of cleaved caspase-1 (Fig. 1) and release of mature IL-1 β (LPS+ATP: 875±13.38 and LPS+Dantrolene+ATP: 351.3±3.98). Intraperitoneal injection of dantrolene (5mg/Kg) significantly suppressed serum transaminases and hemorrhage in LPS/D-Gal hepatitis, and suppressed fibrosis formation by TAA. Conclusion: Dantrolene inhibits inflammasome activation in PD-332991 vitro and prevents hepatitis and liver fibrosis in vivo. Inhibition of ryanodine receptors may be a promising approach in acute and chronic liver diseases. Disclosures: Wajahat Z. Mehal – Management Position: Gloabl BioReserach Partners The following people have nothing to disclose: Md Kaimul Ahsan The hepatic injury due acetaminophen (APAP) is augmented by gram-negative bacterial endotoxin (lipopolysaccharide: LPS). However, the understanding of the mechanisms of this clinically significant problem and the early predictors of cellular stress/injury is inadequate. Upon stimulation by LPS, hepatic stellate cells (HSCs), which are located close to hepatocytes, produce an array of cytokines that can affect survival of the latter. Therefore, we hypothesized JQ1 that

mediators released by LPSstimulated HSCs might be responsible in augmenting APAP-induced liver injury. Rats (n=6 each) were administered 5 mg/kg LPS or vehicle (PBS) (i. p. ), and 1h later 200 mg/kg ApAp or PBS (i. p. ). Control rats received PBS at both time points. All rats were sacrificed at 6h after

APAP or second PBS injection. Histology and electron microscopy demonstrated mild liver injury due to LPS in the presence of strong endoplasmic reticulum (ER) stress, but serum ALT and AST did not show significant increase. APAP by itself also elicited mild liver injury (mild increase in ALT and AST) and low level ER stress. However, there was a MCE公司 strong autophagic response with augmentation of the hepatic injury when APAP was administered after LPS. These effects were congruent with increased expression of CHOP (ER stress), LC3 II formation (autophagy) and caspase 3 activation (apoptosis), and were consistent with apoptotic hepatocytes in close proximity to HSCs. Notably, the liver injury was accompanied by proportionate increases in the serum levels of hepatocyte survival factor “augmenter of liver regeneration (ALR)”. The increase in serum ALR was more consistent than that of ALT/AST. In vitro, LPS-treated HSCs inhibited DNA and protein synthesis, induced ER stress (CHOP expression) and autophagy (LC3 II expression), and caused low level apoptosis (TUNEL staining) of hepatocytes.