Background And Objective: Nitric oxide and reactive oxygen species have been implicated in several pathophysiological events leading to fibrosis and cirrhosis. The aim of the present study was to investigate the possible contribution of peroxynitrite (formed by the interaction of nitric oxide and superoxide anion) in the pathophysiology of cirrhosis.
Methods: Twenty-six cirrhotic patients classified as Child-Pugh A, and seven as Child-Pugh B, were included in the study, and nine healthy volunteers served as controls. Levels of nitrite/nitrate (NOx), thiobarbituric acid-reactive substances (TBARS), nitrotyrosine (peroxynitrite marker), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were measured in blood samples.
Results: NOx, TBARS, CAT, SOD and GSH levels were higher in cirrhosis patients than in the controls (NOx: 0.17 ± 0.02, 0.95 ± 0.12, 1.3 ± 0.1; TBARS: 2.0 ± 0.05, 4.6 ± 0.3, 5 ± 0.3; CAT: 1.8 ± 0.1, 4 ± 0.3, 4.5 ± 0.4; SOD: 1.8 ± 0.2, 4.8 ± 0.5, 7 ± 0.4; and GSH: 1.3 ± 0.05, 3.6 ± 0.3, 4.5 ± 0.6 in controls, and Child-Pugh A and B patients, respectively). However, there were no differences in nitrotyrosine levels across these groups (controls: 11.4 ± 0.4; Child-Pugh A: 11.1 ± 0.4; Child-Pugh B: 11.9 ± 1.6). NOx levels showed significant and strongly positive correlations with TBARS, SOD, CAT and GSH levels. In contrast, no correlations were found between either NOx or TBARS and nitrotyrosine levels.
Conclusion: Nitric oxide and reactive oxygen species, but not peroxynitrite, are overproduced in patients with cirrhosis in spite of evidence of an increase in antioxidant defenses. This suggests that therapeutic measures aimed at attenuating oxidative stress as well as increasing antioxidant defenses may well benefit patients with cirrhosis.
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