title: Sequential changes in redox status and nitric oxide synthases expression in the liver after bile duct ligation.
abstract: 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.
authors.affiliation: Departamento de Fisiología y Farmacología, Edificio Departamental, Campus Miguel de Unamuno, Universidad de Salamanca, 7007 Salamanca, Spain.
authors.forename: M José
authors.initials: MJ
authors.lastname: Vázquez-Gil
authors.forename: M José
authors.initials: MJ
authors.lastname: Mesonero
authors.forename: Olga
authors.initials: O
authors.lastname: Flores
authors.forename: Manuela
authors.initials: M
authors.lastname: Criado
authors.forename: Froilán
authors.initials: F
authors.lastname: Hidalgo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Arévalo
authors.forename: Angel
authors.initials: A
authors.lastname: Sánchez-Rodríguez
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Tuñón
authors.forename: José M
authors.initials: JM
authors.lastname: López-Novoa
authors.forename: A
authors.initials: A
authors.lastname: Esteller
mesh_terms: D000818:Animals; D017734:Bile Ducts, Extrahepatic / Q000601:surgery*; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000032:analysis / Q000378:metabolism; D007124:Immunoenzyme Techniques; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D006909:Hydroxyproline