Radical oxygen species and bile secretion

BASIGLIO, CL; TOLEDO, FD; SANCHEZ POZZI, EJ; ROMA, MG

Systems Biology of Oxidative Stress (SBOS): Free Radicals and Anti-oxidants Biology

Springer Verlag

Lugar: Berlin; Año: 2014;

Oxidative stress is a common feature in most hepatopathies. Accumulating evidencesindicate that reactive oxygen species (ROS) induce a number of functional changes eitherdeleterious or adaptive in the capability of the hepatocytes to produce bile and to secreteexogenous and endogenous compounds. This review is aimed to describe the mechanismsinvolved in these changes. For this purpose, we will summarize:1) The current evidence that acutely-induced oxidative stress is cholestatic, by describing themechanisms underlying the hepatocyte secretory failure, including the disorganization ofthe actin cytoskeleton and its most noticeable consequences, i.e. the impairment of tightjunctionalstructures and the endocytic internalization of canalicular transporters relevantto bile formation.2) The role for oxidative-stress-activated signalling pathways in the pathomechanismsdescribed above, particularly those involving Ca2+ elevation and its consequent activationvia Ca2+ of ?classical? and ?novel? PKC isoforms.3) The mechanisms involved in the adaptive response against oxidative stress mediated byROS-responsive transcription factors, such as up-regulation of GSH synthesis pathway,antioxidant enzymes and hepatocellular efflux pumps.4) The consequences on hepatocellular secretory function when this adaptive response can besurpassed by the sustained/high production of ROS. This deleterious effects includetranscriptional and posttranscriptional changes in the expression of transporters relevant tobile formation, as has been shown to occur, for example, after long-term administration ofaluminium to rats, in the Long-Evans Cinnamon rat (a model of chronic hepatic copperaccumulation mimicking Wilson´s disease), and in ischemia-reperfusion injury.