Evidence of an increased nitric oxide production in primary biliary cirrhosis

Abstract

Evidence of an increased nitric oxide production in primary biliary cirrhosis. / Battista S; Bar F; Mengozzi G; Pollet C; Torchio M; Cavalli G; Rosina F; David E; Cutrin JC; Cavalieri B; Poli G; Molino G.. -In: AMERICAN JOURNAL OF GASTROENTEROLOGY. -ISSN 0002-9270. -96(2001), pp. 869-875. Original Citation:Evidence of an increased nitric oxide production in primary biliary cirrhosis. Terms of use:Open Access (Article begins on next page) Anyone can freely access the full text of works made available as "Open Access". Works made available under a Creative Commons license can be used according to the terms and conditions of said license. Use of all other works requires consent of the right holder (author or publisher) if not exempted from copyright protection by the applicable law. Availability: This is the author's manuscriptAlthough possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS:Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS:Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55 Ϯ 1.75 arbitrary units vs 1.95 Ϯ 0.57 and 0.84 Ϯ 0.34, p ϭ 0.0004 and p Ͻ 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7 Ϯ 192.0 g/L vs 51.1 Ϯ 34.3 and 38.0 Ϯ 11.5, p Ͻ 0.0001 and p Ͻ 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS:Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide. (Am J Gastroenterol 2001;96:869 -875.

Polymorphisms of genes related to endothelial cells are associated with primary biliary cirrhosis patients of Cretan origin

“…The endothelial nitric oxide synthase (eNOS) gene has been previously studied in PBC and has been associated with disease severity rather than disease susceptibility [20,22]. With regard to the eNOS exon7 894G/T polymorphism, contrary to our findings, no association with the disease development was detected although an association of allele T with progressive disease has been detected in that study.…”

“…In experimental animal models, it has been showed that the eNOS enzymatic activity may be markedly affected in liver injury, leading to increased sinusoidal resistance [18,19]. Circulating levels of NO are increased in patients with more severe disease [20], but the relative roles of eNOS and iNOS expression in PBC are still unknown. NO produced from eNOS is clearly beneficial to the liver for its role in maintaining perfusion, and preventing platelet adhesion, thrombosis, and PMN accumulation.…”

Elevated serum nitric oxide metabolites in biliary atresia

“…Overproduction of NO in cirrhotic patients is related to the severity of liver damage [19]. Battista et al [9] reported that enhanced NO production in primary biliary cirrhosis could be related to the development of a strong inflammation and at least partially to neutrophil activation. In addition, NO upregulation is dependent on the inflammatory stage of liver cirrhosis [20].…”

“…Recently, it has been illustrated that nitric oxide (NO) produced through inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of bile duct injury in primary biliary cirrhosis [9,10]. However, the role of NO production towards liver fibrosis in BA patients has never been reported.…”

Therapeutic efficacy of decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis

“…Increased levels of NO in the sera, and increased expression of inducible nitric oxidase synthase (iNOS) at the site of damaged BECs have been reported in PBC. [6][7][8] Indeed, NO may be involved in the pathogenesis of several autoimmune diseases by causing damage to mitochondria and inducing several proinflammatory cytokines. 9 From the therapeutic viewpoint, PBC represents a unique autoimmune disease, because immune suppressive agents are ineffective in PBC, although immune suppressor drugs are widely used, effectively, for other autoimmune diseases.…”