title: Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis.
abstract: Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations, with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts, lipids, and nutrients, as well as destruction of membrane lipids and mitochondrial dysfunction. Both oxidative and nitrosative stress are associated with ongoing manifestations of the disease. In particular, abnormalities in nitric oxide metabolism and thiol oxidation already occur at early stages, thus leading to the hypothesis that these biochemical events play a pathogenic role in primary biliary cirrhosis. Moreover, the association of these metabolic abnormalities with the progression of the disease may indicate some biochemical parameters as early diagnostic markers of disease evolution, and may open up the potential for pharmacological intervention to inhibit intra- and extra-cellular stress events for resuming hepatocellular functions. The following paragraphs summarize the current knowledge by outlining molecular mechanisms of the disease related to these stress events.
authors.affiliation: Ignazio Grattagliano, Italian College of General Practitioners, 50100 Florence, Bari 70124, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Grattagliano
authors.affiliation: Ignazio Grattagliano, Italian College of General Practitioners, 50100 Florence, Bari 70124, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calamita
authors.affiliation: Ignazio Grattagliano, Italian College of General Practitioners, 50100 Florence, Bari 70124, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cocco
authors.affiliation: Ignazio Grattagliano, Italian College of General Practitioners, 50100 Florence, Bari 70124, Italy.
authors.forename: David Q-H
authors.initials: DQ
authors.lastname: Wang
authors.affiliation: Ignazio Grattagliano, Italian College of General Practitioners, 50100 Florence, Bari 70124, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism* / Q000473:pathology*; D008928:Mitochondria / Q000473:pathology; D009569:Nitric Oxide / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013879:Thioredoxins / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D013879:Thioredoxins; D005978:Glutathione; D009584:Nitrogen
keywords: Aquaporins; Bile salts; Chronic cholestasis; Glutathione; Mitochondria; Nitrosothiols; Nitrotyrosine; Protein sulfhydryls; Thioredoxin