Wistar adult rats were bile duct ligated and were scanned before BDL and weekly thereafter for 8 weeks. In vivo localized 1H and 31P spectroscopy was performed on a 9. 4T system. Metabolite concentrations were calculated using water as internal reference for the 1 H data and ۷ATP for the 31 P data. DTI (diffusion tensor imaging) was performed and diffusivity values (ADC coefficient) were derived and measured in R〇Is positioned in: cortex, striatum and hippocampus. All BDL rats showed increased plasma ammonia of 140±29μM. Using in vivo 1H MRS we measured a two fold increase of brain glutamine

PD0325901 clinical trial in all BDL rats. As a compensatory effect for osmotic imbalance created by glutamine increase, other brain osmolytes decreased: Myoinositol being the first one (−35%), followed by taurine and choline (−20% and −40%) as well as creatine (−20%), a metabolite involved in energy metabolism but recently described in osmoregulation and neuromodulation. Phosphocreatine, a metabolite involved in energy metabolism, was constant over time. ADC values showed an increase (+10%) over the first 8 weeks post-BDL, suggesting that mild edema develops in spite of ongoing osmotic regulation in agreement with our previous

results. 31P MRS data showed a gradual increase of Phosphocreatine/yATP ratios, meaning that there was a gradual decrease of ۷ATP (−10%) since phosphocreatine values were constant over time. Our work suggests that the osmotic imbalance created by the continuous increase of glutamine may be partially compensated by a concomitant decrease of other idiogenic osmolytes HM781-36B ic50 resulting in minimal brain edema. It is unlikely that the residual brain edema is due to energy disturbances. Rather, high concentrations of the osmotically active glutamine may be the principal cause of the minimal brain edema increasingly recognized in CLD. Disclosures: The

following people have nothing to disclose: Cristina Cudalbu, Olivier Braissant, Arjun Jayaswal, Rolf Gruetter, Valerie A. McLin many Estrogen-induced cholestasis may develop in susceptible individuals during pregnancy, oral contraceptive use, or hormone replacement therapy. It is characterized by an impaired uptake and excretion of bile acids (BA) due to changes in the expression of key hepatocyte transporters. Heme oxygenase-1 (HM〇X-1) is the inducible rate-limiting enzyme in heme catabolism. The induction of HM〇X-1 by its substrate, heme, is mediated via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). HM〇X-1 induction can protect the liver from toxic, oxidative and inflammatory insults, however, its role in cholestasis remains unknown. The objective of this study was to investigate the effect of HM〇X-1 induction by heme on ethinylestradiol (EE)-induced cholestasis and possible underlying mechanisms.