A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats
Rodríguez, Sarai (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Raurell, Imma (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Torres-Arauz, Manuel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García Lezana, Teresa (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Genescà Ferrer, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martell, María (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	Statins present many beneficial effects in chronic liver disease, but concerns about safety exist. We evaluated the hepatic effects of a nitric oxide-releasing atorvastatin (NCX 6560) compared to conventional statins. Simvastatin, atorvastatin and NCX 6560 were evaluated in four-week bile duct-ligated rats (BDL) simulating decompensated cirrhosis and in thirteen-week carbon tetrachloride (CCl) intoxicated rats, a model of early cirrhosis. In the BDL model, simvastatin treated rats showed high mortality and the remaining animals presented muscular and hepatic toxicity. At equivalent doses, NCX 6560 eliminated hepatic toxicity and reduced muscular toxicity (60-74%) caused by atorvastatin in the more advanced BDL model; toxicity was minimal in the CCl model. Atorvastatin and NCX 6560 similarly reduced portal pressure without changing systemic hemodynamics in both models. Atorvastatin and NCX 6560 caused a mild decrease in liver fibrosis and inflammation and a significant increase in intrahepatic cyclic guanosine monophosphate. NCX 6560 induced a higher intrahepatic vasoprotective profile (activated endothelial nitric oxide synthase and decreased platelet/endothelial cell adhesion molecule-1), especially in the CCl model, suggesting a higher benefit in early cirrhosis. In conclusion, NCX 6560 improves the liver profile and portal hypertension of cirrhotic rats similarly to conventional statins, but with a much better safety profile.
Grants:	Instituto de Salud Carlos III PI12/01759 Instituto de Salud Carlos III PI13/01289
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 7 (01 2017) , ISSN 2045-2322

DOI: 10.1038/srep40461
PMID: 28084470

12 p, 1.0 MB

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