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World J Gastroenterol. Jan 14, 2008; 14(2): 236-242
Published online Jan 14, 2008. doi: 10.3748/wjg.14.236
Elevated nitric oxide and 3’,5’ cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis
Cíntia Siqueira, Miguel Carneiro de Moura, Ana Julia Pedro, Paula Rocha
Cíntia Siqueira, Miguel Carneiro de Moura, Center of Gastroenterology, Institute of Molecular Medicine, School of Medicine, University of Lisbon, Portugal
Miguel Carneiro de Moura, Gastroenterology and Hepatology Unit, University Hospital of Santa Maria, Lisbon, Portugal
Paula Rocha, Ana Júlia Pedro, Department of Medicine II, University Hospital of Santa Maria, Lisbon, Portugal
Correspondence to: Cíntia Siqueira, PhD, Center of Gastro-enterology, Institute of Molecular Medicine, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal. cintiasiqueira@fm.ul.pt
Telephone: +351-217-647570
Fax: +351-217-932605
Received: August 9, 2007
Revised: October 9, 2007
Published online: January 14, 2008
Abstract

AIM: To evaluate whether serum levels of nitric oxide (NO) and plasma levels of cyclic guanosine monophosphate (cGMP) and total glutathione (GSH) are altered in patients with alcoholic cirrhosis and to examine their correlation with the severity of liver disease.

METHODS: Twenty-six patients with alcoholic liver cirrhosis were studied. Serum levels of NO and plasma levels of cGMP and GSH were measured in 7 patients with compensated alcoholic cirrhosis (Child-Pugh A) and 19 patients with advanced cirrhosis (Child-Pugh B and C). The model for end-stage liver disease (MELD) score was evaluated. Sixteen healthy volunteers served as controls. Liver enzymes and creatinine levels were also tested.

RESULTS: NO and cGMP levels were higher in patients with Child-Pugh B and C cirrhosis than in Child-Pugh A cirrhosis or controls (NO: 21.70 ± 8.07 vs 11.70 ± 2.74; 21.70 ± 8.07 vs 7.26 ± 2.47 &mgr;mol/L, respectively; P < 0.001) and (cGMP: 20.12 ± 6.62 vs 10.14 ± 2.78; 20.12 ± 6.62 vs 4.95 ± 1.21 pmol/L, respectively; P < 0.001). Total glutathione levels were lower in patients with Child-Pugh B and C cirrhosis than in patients with Child-Pugh A cirrhosis or controls (16.04 ± 6.06 vs 23.01 ± 4.38 or 16.04 ± 6.06 vs 66.57 ± 26.23 &mgr;mol/L, respectively; P < 0.001). There was a significant correlation between NO and cGMP levels in all patients with alcoholic cirrhosis. A significant negative correlation between reduced glutathione/glutathione disulfide and the MELD score was found in all cirrhotic patients.

CONCLUSION: Our results suggest a role for oxidative stress in alcoholic liver cirrhosis, which is more significant in decompensated patients with higher levels of NO and cGMP and lower GSH levels than in compensated and control patients. Altered mediator levels in decompensated patients may influence the hemodynamic changes in and progression of liver disease.

Keywords: Oxidative stress, Nitric oxide, Alcoholic cirrhosis, Fibrosis, Model for end-stage liver disease