Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome

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 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). Conclusion. 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.