Reduced nicotinamide adenine dinucleotide phosphate oxidase mediates fibrotic and inflammatory effects of leptin on hepatic stellate cells

Samuele De Minicis, Ekihiro Seki, Christoph Oesterreicher, Bernd Schnabl, Robert F. Schwabe, David A. Brenner – 24 November 2008 – Although leptin induces fibrotic activity in hepatic stellate cells (HSCs), the mechanisms are not entirely understood. To investigate the potential role of reduced nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and reactive oxygen species (ROS) in leptin signaling in HSCs, we analyzed leptin‐induced intracellular signaling pathways in primary wild‐type (WT), p47, and signal transducer and activator of transcription protein 3 (STAT3)‐deleted HSCs.

Ca2+‐dependent protein kinase C isoforms are critical to estradiol 17β‐D‐glucuronide–induced cholestasis in the rat

Fernando A. Crocenzi, Enrique J. Sánchez Pozzi, María Laura Ruiz, Andrés E. Zucchetti, Marcelo G. Roma, Aldo D. Mottino, Mary Vore – 24 November 2008 – The endogenous estradiol metabolite estradiol 17β‐D‐glucuronide (E217G) induces an acute cholestasis in rat liver coincident with retrieval of the canalicular transporters bile salt export pump (Bsep, Abcc11) and multidrug resistance‐associated protein 2 (Mrp2, Abcc2) and their associated loss of function.

Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors

Haruaki Shirakawa, Akihiro Matsumoto, Satoru Joshita, Michiharu Komatsu, Naoki Tanaka, Takeji Umemura, Tetsuya Ichijo, Kaname Yoshizawa, Kendo Kiyosawa, Eiji Tanaka, Nagano Interferon Treatment Research Group – 24 November 2008 – The interferon sensitivity determining region (ISDR) of the hepatitis C virus (HCV) and T‐helper type 1 and type 2 (Th1/Th2) ratio were analyzed along with other host and viral factors for their ability to predict the response of patients with chronic hepatitis C to pegylated interferon alpha‐2b (Peg‐IFN) and ribavirin (RBV) combination therapy.

Superoxide produced by Kupffer cells is an essential effector in concanavalin A–induced hepatitis in mice

Hiroyuki Nakashima, Manabu Kinoshita, Masahiro Nakashima, Yoshiko Habu, Satoshi Shono, Takefumi Uchida, Nariyoshi Shinomiya, Shuhji Seki – 24 November 2008 – Although concanavalin A (Con‐A)‐induced experimental hepatitis is thought to be induced by activated T cells, natural killer T (NKT) cells, and cytokines, precise mechanisms are still unknown. In the current study, we investigated the roles of Kupffer cells, NKT cells, FasL, tumor necrosis factor (TNF), and superoxide in Con‐A hepatitis in C57BL/6 mice.

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