Sequential changes in redox status and nitric oxide synthases expression in
the liver after bile duct ligation
Vazquez-Gil MJ, Mesonero MJ, Flores O, Criado M, Hidalgo F, Arevalo MA,
Sanchez-Rodriguez A, Tunon MJ, Lopez-Novoa JM, Esteller A
Life Sci 2004; 75(6): 713-32
Bile duct ligation (BDL) in rats induces portal fibrosis. This process has been
linked to changes in the oxidative state of the hepatic cells and in the
production of nitric oxide. Our objective was to find possible temporal
connections between hepatic redox state, NO synthesis and liver injury. In this
work we have characterized hepatic lesions 17 and 31 days after BDL and
determined changes in hepatic function, oxidative state, and NO production. We
have also analyzed the expression and localization of inducible NO synthase
(NOS2) and constitutive NO synthase (NOS3). After 17 and 31 days from ligature,
lipid peroxidation is increased and both plasma concentration and biliary
excretion of nitrite+nitrate are rised. 17 days after BDL both NOS2 and NOS3 are
expressed intensely and in the same regions. 31 days after BDL, the expression
of NOS2 remains elevated and is localized mostly in preserved hepatocytes in
portal areas and in neighborhoods of centrolobulillar vein. NOS3 is localized in
vascular regions of portal spaces and centrolobulillar veins and in preserved
sinusoids and although its expression is greater than in control animals (34%),
it is clearly lower (50%) than 17 days after BDL. The time after BDL is crucial
in the study of NO production, intrahepatic localization of NOS isoforms
expression, and cell type involved, since all these parameters change with time.
BDL-induced, peroxidation and fibrosis are not ligated by a cause-effect
relationship, but rather they both seem to be the consequence of common
inductors.
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