Increased ketone bodies also stabilize CYP2E1 protein, resulting in a marked increase of APAP bioactivation to generate the hepatotoxic metabolite, which causes liver injury (Fig. 8). We found that message levels of a number of cytokines were similar in liver tissues and

liver mononuclear cells (in which NKT cells are enriched) isolated from APAP-treated WT and CD1d−/− mice (data not shown). These results suggest that APAP treatment does not trigger NKT cells to produce protective cytokines. Our data do not support an active protective role for NKT cells, but rather that the lack of NKT cells renders mice more susceptible to AILI. This is the first study to examine the specific role of NKT cells in AILI. The findings provide further insights into the underlying mechanisms of drug-induced liver injury, as well as other liver conditions in which CYP2E1-mediated ROS generation plays an important pathological role.41 Aside from genetic conditions, such see more as abetalipoproteinemia, lipid antigens, bacterial, and viral pathogens have been demonstrated to activate NKT cells, which leads to decreased cell number.42 Under such situations, NKT cell deficiency may

result in increased susceptibility to metabolic stress, as learn more well as hepatotoxin-induced liver injury. The authors thank Drs. Chris Franklin and Don Backos for their assistance with glutathione cysteine ligase western blotting analysis. The authors thank Casey Trambly for conducting the proteasome and CYP2E1 activity assays and Dr. James Galligan for assistance in CYP2E1 IHC. Special thanks to Dr. Sean Colgan for the generous use of HPLC instrumentation and Brittelle Bowers and Adrianne Burgess for their technical assistance with HPLC setup. Additional Supporting Information may be found in the online version of this article.

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“There is little information on the early kinetics of hepatitis delta selleckchem virus (HDV) and hepatitis B surface antigen (HBsAg) during interferon-α therapy. Here a mathematical model was developed and fitted to frequent HDV and HBsAg kinetic data from 10 patients during the first 28 weeks of pegylated-interferon-α2a (peg-IFN) therapy. Three patients achieved a complete virological response (CVR), defined as undetectable HDV 6 months after treatment stopped with loss of HBsAg and anti-HBsAg seroconversion. After initiation of therapy, a median delay of 9 days (interquartile range [IQR]: 5-15) was observed with no significant changes in HDV level. Thereafter, HDV declined in a biphasic manner, where a rapid first phase lasting for 25 days (IQR: 23-58) was followed by a slower or plateau second phase. The model predicts that the main effect of peg-IFN is to reduce HDV production/release with a median effectiveness of 96% (IQR: 93-99.8). Median serum HDV half-life (t1/2) was estimated as 2.9 days (IQR: 1.5-5.3) corresponding to a pretreatment production and clearance of about 1010 (IQR: 109.7-1010.7) virions/day.