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Treatment of experimental animals with prototypical enzyme inducers represents a useful tool to characterize the role of different isozymes in drug metabolism and to improve our knowledge on factors regulating their synthesis at the transcriptional level. The effect of model enzyme inducers on phase II (conjugating) enzyme families, including(More)
OBJECTIVE The endogenous, cholestatic metabolite estradiol 17ß-D-glucuronide (E(2)17G) induces endocytic internalization of the canalicular transporters relevant to bile formation, Bsep and Mrp2. We evaluated here whether MAPKs are involved in this effect. DESIGN ERK1/2, JNK1/2, and p38 MAPK activation was assessed by the increase in their phosphorylation(More)
Oxidative stress is a common feature in most hepatopathies. In recent years, evidence has accumulated that reactive oxygen species (ROS) induce a number of functional changes either deleterious or adaptive in the capability of the hepatocytes to produce bile and to secrete exogenous and endogenous compounds. This review is aimed to describe the mechanisms(More)
UNLABELLED Estradiol 17ß-D-glucuronide (E17G) induces acute cholestasis in rat with endocytic internalization of the canalicular transporters bile salt export pump (Abcb11) and multidrug resistance-associated protein 2 (Abcc2). Classical protein kinase C (cPKC) and PI3K pathways play complementary roles in E17G cholestasis. Since non-conjugated estradiol is(More)
In estradiol 17β-d-glucuronide (E17G)-induced cholestasis, the canalicular hepatocellular transporters bile salt export pump (Abcb11) and multidrug-resistance associated protein 2 (Abcc2) undergo endocytic internalization. cAMP stimulates the trafficking of transporter-containing vesicles to the apical membrane and is able to prevent internalization of(More)
The ability of the liver and small intestine for secretion of dinitrophenyl-S-glutathione (DNP-SG), a substrate for multidrug resistance-associated protein 2 (Mrp2), into bile and lumen, respectively, as well as expression of Mrp2 in both tissues, were assessed in 70-75% hepatectomized rats. An in vivo perfused intestinal model was used. A single i.v. dose(More)
TO THE EDITOR: we have read with interest the recent paper by Sekine et al. (8), showing that redox status is a key determinant of dynamic localization of the canalicular transporter Mrp2 in hepatocytes. Although we regard this work as novel and relevant, we believe their results can be reinterpreted when better contextualized within the present body of(More)
The ability of the kidney and small intestine to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for the multidrug resistance-associated proteins (Mrps), was assessed in bile duct-ligated (BDL) rats 1, 7, and 14 days after surgery, using an in vivo perfused jejunum model with simultaneous urine collection. A single(More)
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