INVESTIGADORES
SANCHEZ POZZI Enrique Juan
artículos
Título:
Oxidative stress: A radical way to stop making bile
Autor/es:
ROMA, MARCELO G; SANCHEZ POZZI, EJ
Revista:
Annals of Hepatology
Editorial:
México : Ediciones Medicina y Cultura
Referencias:
Lugar: Mexico; Año: 2008 vol. 7 p. 16 - 33
Resumen:
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 involved in these alterations. For this
purpose, we will summarize: 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, the impairment of
tight-junctional structures and the endocytic internalization of
canalicular transporters relevant to bile formation. 2) The role for oxidative-stress-activated
signalling pathways in the pathomechanisms described above,
particularly those involving Ca2+ elevation and its consequent
activation of Ca2+ -dependent PKC isoforms. 3) The mechanisms involved
in the adaptive response against oxidative stress
mediated by ROS-responsive transcription factors, involving
up-regulation of GSH-synthesizing enzymes, GSH-detoxifying enzymes and
the hepatocellular efflux pumps; this response enhances the
co-coordinated inactivation by GSH conjugation of lipid peroxides and
their further cellular extrusion. 4) The manner this adaptive response
can be surpassed by the sustained production of ROS, thus inducing
transcriptional and posttranscriptional changes in 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.