Implications of oxidative stress in pathogenesis of cholestasis.
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Date
2011-10
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Abstract
Cholestasis results from both genetic and acquired conditions causing disordered bile secretion and flow resulting in accumulation of toxic cholephiles in the blood. Prolonged and unrelieved
cholestasis leads to liver injury, fibrosis and failure. Recent advances in understanding of the
molecular mechanism of cholestasis, including function of biliary transporters and their
regulation, have provided significant insights into pathophysiological derangements in
cholestasis. Oxidative stress, caused by unchecked and dysregulated accumulation of reactive
oxygen species (ROS) has emerged as an important contributor to cholestatic liver injury.
Adaptive mechanisms in the liver through participation of redox responsive transcription
factors, mainly the Nfr2/Keap1 system, as well as NF-kB and AP-1 are important. Oxidative
stress induced actin disorganization with tight-junction impairment and transporter
internalization have been observed to occur along with activation of Ca2+ dependent protein
kinase C isoforms (cPKCs) in cholestasis related oxidative stress, that plays an important role
in secretory failure . Animal models of cholestasis have been developed and inflammation has
been found to play a significant role in cholestasis induced liver injury. A complete
understanding of the redox sensitive signaling pathways involved in cholestasis is very much essential in order to have a more complete picture for better insight into the selective therapeutic strategies to abrogate ROS mediated harmful pathways, or to enhance the protective ones.
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Keywords
Oxidative stress, reactive oxygen species, cholestasis, liver injury
Citation
Pal Suparna, Ghatak Subhadip, Chowdhury Abhijit. Implications of oxidative stress in pathogenesis of cholestasis. Tropical Gastroenterology. 2011 Jan; 32(suppl1): S11-22.