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Radical Oxygen Species and Bile Secretion

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Systems Biology of Free Radicals and Antioxidants

Abstract

Oxidative stress is a common feature in most hepatopathies. Accumulating evidences indicate 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 involved in these changes. For this purpose, we will summarize:

  1. 1.

    The current evidence that acutely induced oxidative stress is cholestatic, by describing the mechanisms underlying the hepatocyte secretory failure, including the disorganization of the actin cytoskeleton and its most noticeable consequences, that is, the impairment of tight-junctional structures and the endocytic internalization of canalicular transporters relevant to bile formation.

  2. 2.

    The role for oxidative-stress-activated signalling pathways in the pathomechanisms described above, particularly those involving Ca2+ elevation and its consequent activation via Ca2+ of “classical” and “novel” PKC isoforms.

  3. 3.

    The mechanisms involved in the adaptive response against oxidative stress mediated by ROS-responsive transcription factors, such as upregulation of GSH synthesis pathway, antioxidant enzymes, and hepatocellular efflux pumps.

  4. 4.

    The consequences on hepatocellular secretory function when this adaptive response can be surpassed by the sustained/high production of ROS. This deleterious effects include transcriptional and posttranscriptional changes in the expression of transporters relevant to bile formation, as has been shown to occur, for example, after long-term administration of aluminum to rats, in the Long-Evans Cinnamon rat (a model of chronic hepatic copper accumulation mimicking Wilson’s disease), and in ischemia-reperfusion injury.

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Authors and Affiliations

  1. Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas (CONICET – U.N.R.), Suipacha 570, S2002LRL, Rosario, Argentina

    Cecilia L. Basiglio, Flavia D. Toledo, Enrique J. Sánchez Pozzi & Marcelo G. Roma

Authors
  1. Cecilia L. Basiglio
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  2. Flavia D. Toledo
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  3. Enrique J. Sánchez Pozzi
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  4. Marcelo G. Roma
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Corresponding author

Correspondence to Marcelo G. Roma .

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Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Basiglio, C.L., Toledo, F.D., Sánchez Pozzi, E.J., Roma, M.G. (2014). Radical Oxygen Species and Bile Secretion. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_140

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