Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis

Ignazio Grattagliano, Giuseppe Calamita, Tiziana Cocco, David Q.H. Wang, Piero Portincasa

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5746-5759
Number of pages14
JournalWorld Journal of Gastroenterology
Volume20
Issue number19
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Keywords

  • Aquaporins
  • Bile salts
  • Chronic cholestasis
  • Glutathione
  • Mitochondria
  • Nitrosothiols
  • Nitrotyrosine
  • Protein sulfhydryls
  • Thioredoxin

ASJC Scopus subject areas

  • Gastroenterology

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