ArticleProceedings of the National Academy of Sciences of the United States of America2001
NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 128 citations in OpenAlex.
- Review
- Liver-targeted delivery of asiatic acid nanostructured lipid carrier for the treatment of liver fibrosis.Drug delivery · 2021Article
- Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy.JHEP reports : innovation in hepatology · 2021Review
- Phosphodiesterases in the Liver as Potential Therapeutic Targets of Cirrhotic Portal Hypertension.International journal of molecular sciences · 2020Review
- Managing portal hypertension in patients with liver cirrhosis.F1000Research · 2018Review
- A novel liver-targeted nitric oxide donor UDCA-Thr-NO protects against cirrhosis and portal hypertension.American journal of translational research · 2018Article
- Intrahepatic vascular changes in non-alcoholic fatty liver disease: Potential role of insulin-resistance and endothelial dysfunction.World journal of gastroenterology · 2017Review
- Homing in on the hepatic scar: recent advances in cell-specific targeting of liver fibrosis.F1000Research · 2016Review
- AP-1 Inhibition by SR 11302 Protects Human Hepatoma HepG2 Cells from Bile Acid-Induced Cytotoxicity by Restoring the NOS-3 Expression.PloS one · 2016Article
- Future therapy of portal hypertension in liver cirrhosis - a guess.F1000prime reports · 2014Review
- U12, a UDCA derivative, acts as an anti-hepatoma drug lead and inhibits the mTOR/S6K1 and cyclin/CDK complex pathways.PloS one · 2014Article
- Current concepts on the role of nitric oxide in portal hypertension.World journal of gastroenterology · 2013Review
- NCX 1000 Alone or in Combination with Vitamin E Reverses Experimental Nonalcoholic Steatohepatitis in the Rat Similarly to UDCA.International journal of hepatology · 2011Article
- Bile-acid-activated farnesoid X receptor regulates hydrogen sulfide production and hepatic microcirculation.World journal of gastroenterology · 2009Article
- Advances in antifibrotic therapy.Expert review of gastroenterology & hepatology · 2008Review
- Design, synthesis, and antihepatocellular carcinoma activity of nitric oxide releasing derivatives of oleanolic acid.Journal of medicinal chemistry · 2008Article
- Endothelial nitric oxide synthase is a critical factor in experimental liver fibrosis.International journal of experimental pathology · 2008Article
- Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species.Hepatology (Baltimore, Md.) · 2008Article
- Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats.World journal of gastroenterology · 2006Article
- Acetaminophen hepatotoxicity: NO to the rescue.British journal of pharmacology · 2004Article
Corrections and comments
- Expression of concern
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Portal hypertension resulting from increased intrahepatic resistance is a common complication of chronic liver diseases and a leading cause of death in patients with liver cirrhosis, a scarring process of the liver that includes components of both increased fibrogenesis and wound contraction. A reduced production of nitric oxide (NO) resulting from an impaired enzymatic function of endothelial NO synthase and an increased contraction of hepatic stellate cells (HSCs) have been demonstrated to contribute to high intrahepatic resistance in the cirrhotic liver. 2-(Acetyloxy) benzoic acid 3-(nitrooxymethyl) phenyl ester (NCX-1000) is a chemical entity obtained by adding an NO-releasing moiety to ursodeoxycholic acid (UDCA), a compound that is selectively metabolized by hepatocytes. In this study we have examined the effect of NCX-1000 and UDCA on liver fibrosis and portal hypertension induced by i.p. injection of carbon tetrachloride in rats. Our results demonstrated that although both treatments reduced liver collagen deposition, NCX-1000, but not UDCA, prevented ascite formation and reduced intrahepatic resistance in carbon tetrachloride-treated rats as measured by assessing portal perfusion pressure. In contrast to UDCA, NCX-1000 inhibited HSC contraction and exerted a relaxing effect similar to the NO donor S-nitroso-N-acetylpenicillamine. HSCs were able to metabolize NCX-1000 and release nitrite/nitrate in cell supernatants. In aggregate these data indicate that NCX-1000, releasing NO into the liver microcirculation, may provide a novel therapy for the treatment of patients with portal hypertension.
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