title: Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome.
abstract: OBJECTIVE
  To investigate possible abnormalities of vasoactive compounds, nitrative stress, and antioxidant activity of paraoxonase (PONa) in human hepatopulmonary syndrome (HPS), we determined endothelin-1 (ET), nitric oxide (NOx) metabolites, PONa alongside crude plasma nitrotyrosine (NT) as surrogate marker of nitrative stress.
  
  
  METHODS
  Liver cirrhosis (LC) patients with HPS (n = 12) were matched by age, sex, and Child-Pugh score to LC patients without HPS (n = 15) and to healthy controls (CTR) (n = 15); plasma NO2(-) (nitrite) (vascular metabolite), NO3(-) (nitrate) (inflammatory metabolite), and PONa were determined by a colorimetric assay, ET, and NT by immunoassays.
  
  
  RESULTS
  HPS patients showed higher level of ET (p = 0.0002), NO2(-) (p = 0.002), NO3(-) (p = 0.0001), NT (p < 0.0001), and lower PONa (p = 0.0004) than CTR; post-hoc analysis revealed greater ET (p < 0.05) and NO3(-) (p < 0.005) in LC patients with HPS than in LC patients without HPS. NT correlated to Child-Pugh score within HPS (p = 0.04) and LC (p = 0.02).
  
  
  CONCLUSIONS
  Our HPS patients are characterized by elevated plasma levels of ET and NOx metabolites and lower PONa. Reduced PONa alongside elevated NO3(-) and NT suggests that defective antioxidation may favor nitrative stress and both may be implicated in the pathogenesis of HPS.
authors.affiliation: a 1 Haemostasis & Thrombosis Department, Royal Infirmary Edinburgh , Edinburgh, Scotland, UK.
authors.forename: Paul R J
authors.initials: PR
authors.lastname: Ames
authors.affiliation: b 2 Gastroenterology Unit, Ospedale A. Cardarelli Hospital , Napoli, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Guardascione
authors.affiliation: c 3 CEDOC, Chronic Diseases Research Center, NOVA Medical School, Universidade Nova de Lisboa , Lisbon, Portugal.
authors.forename: Joana R
authors.initials: JR
authors.lastname: Batuca
authors.affiliation: c 3 CEDOC, Chronic Diseases Research Center, NOVA Medical School, Universidade Nova de Lisboa , Lisbon, Portugal.
authors.forename: Alessia
authors.initials: A
authors.lastname: Arcaro
authors.affiliation: d 4 Dipartimento di Medicina e Scienze della Salute, Università del Molise , 86010 Campobasso, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gentile
authors.affiliation: b 2 Gastroenterology Unit, Ospedale A. Cardarelli Hospital , Napoli, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Amitrano
mesh_terms: D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D020065:Hepatopulmonary Syndrome / Q000097:blood*; D006801:Humans; D007558:Italy; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood*
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D043303:Aryldialkylphosphatase
keywords: hepatopulmonary syndrome; nitrative stress; paraoxonase