Scandinavian Journal of Gastroenterology. 2015; Early Online, 1–5 SHORT REPORT Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome PAUL R. J. AMES 1 , MARIANNA GUARDASCIONE 2 , JOANA R. BATUCA 3 , ALESSIA ARCARO 3 , FABRIZIO GENTILE 4 & LUCIO AMITRANO 2 1 Haemostasis & Thrombosis Department, Royal Infirmary Edinburgh, Edinburgh, Scotland, UK, 2 Gastroenterology Unit, Ospedale A. Cardarelli Hospital, Napoli, Italy, 3 CEDOC, Chronic Diseases Research Center, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal, and 4 Dipartimento di Medicina e Scienze della Salute, Università del Molise, 86010 Campobasso, Italy Abstract Aim. 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. Material and 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 NO 2  (nitrite) (vascular metabolite), NO 3  (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), NO 2  (p = 0.002), NO 3  (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 NO 3  (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). Conclusion. Our HPS patients are characterized by elevated plasma levels of ET and NOx metabolites and lower PONa. Reduced PONa alongside elevated NO 3  and NT suggests that defective antioxidation may favor nitrative stress and both may be implicated in the pathogenesis of HPS. Key Words: hepatopulmonary syndrome, nitrative stress, paraoxonase Introduction The hepatopulmonary syndrome (HPS) defines the combination of hypoxemia with orthodeoxia and intrapulmonary vascular dilations developing in liver cirrhosis (LC) [1]. The prevalence of HPS in adults with LC ranges from 4% to 29% according to the different cut-offs employed for defining arterial hyp- oxemia [2]. Animal models have provided details on the vascular pathogenesis of HPS [3,4] but the role of vasoactive mediators in human HPS has been explored with contradictory results (reviewed in Ref. [1]). To implement on this issue we undertook a cross-sectional study to evaluate the behavior of paraoxonase (PONa) activity, endothelin-1 (ET), nitric oxide (NOx) metabolites and nitrotyrosine (NT), a surrogate marker of nitrative stress in adults with LC and HPS. Methods Patients and procedures Between January 2004 and December 2009 as many as 166 consecutive patients with LC attending the liver transplant clinic or admitted to the Gastroenter- ology ward of the Antonio Cardarelli Hospital (Naples, Italy) were invited to participate in the study Correspondence: Dr Paul R. J. Ames, MD, MSc, PhD, Haemostasis & Thrombosis Department, Royal Infirmary Edinburgh, UK. Tel: +44 78 16 22 58 26. E-mail: paxmes@aol.com (Received 25 April 2015; revised 5 May 2015; accepted 5 May 2015) ISSN 0036-5521 print/ISSN 1502-7708 online Ó 2015 Informa Healthcare DOI: 10.3109/00365521.2015.1049656 Scand J Gastroenterol Downloaded from informahealthcare.com by 185.58.164.42 on 06/08/15 For personal use only.