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Open AccessArticle

A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease

1
Barcelona Liver Bioservices, 08036 Barcelona, Spain
2
Biochemistry and Molecular Biomedicine Department, Faculty of Biology, University of Barcelona, 08036 Barcelona, Spain
3
Department of Cell Death and Proliferation, IIBB-CSIC/IDIBAPS, 08036 Barcelona, Spain
4
Liver Vascular Biology Research Group, IDIBAPS, 08036 Barcelona, Spain
5
CIBEREHD, 28029 Madrid, Spain
6
Hepatology, Department of Biomedical Research, University of Bern, 3012 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(10), 2358; https://doi.org/10.3390/nu11102358
Received: 29 August 2019 / Revised: 25 September 2019 / Accepted: 29 September 2019 / Published: 3 October 2019
(This article belongs to the Special Issue Nutrition in Liver Cirrhosis and Liver Transplantation)
Inflammation and oxidative stress play a key role in the pathophysiology of advanced chronic liver disease (ACLD) and portal hypertension (PH). Considering the current lack of effective treatments, we evaluated an anti-inflammatory and antioxidant nutraceutical rich in docosahexaenoic acid (DHA) as a possible therapy for ACLD. We investigated the effects of two-week DHA supplementation (500 mg/kg) on hepatic fatty acids, PH, oxidative stress, inflammation, and hepatic stellate cell (HSC) phenotype in rats with ACLD. Additionally, the effects of DHA were evaluated in murine macrophages and human HSC. In contrast to vehicle-treated animals, cirrhotic rats receiving DHA reestablished a healthy hepatic fatty acid profile, which was associated with an improvement in PH. The mechanisms underlying this hemodynamic improvement included a reduction in oxidative stress and inflammation, as well as a marked HSC deactivation, confirmed in human HSC. Experiments with cultured macrophages showed that treatment with DHA protects against pro-inflammatory insults. The present preclinical study demonstrates that a nutraceutical rich in DHA significantly improves PH in chronic liver disease mainly by suppressing inflammation and oxidative stress-driven HSC activation, encouraging its evaluation as a new treatment for PH and cirrhosis. View Full-Text
Keywords: DHA; omega-3; liver fibrosis; liver cirrhosis; hepatic hemodynamics DHA; omega-3; liver fibrosis; liver cirrhosis; hepatic hemodynamics
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Boyer-Diaz, Z.; Domingo, J.C.; De Gregorio, E.; Manicardi, N.; Aristu-Zabalza, P.; Cordobilla, B.; Abad-Jordà, L.; Ortega-Ribera, M.; Fernández-Iglesias, A.; Marí, M.; Bosch, J.; Gracia-Sancho, J. A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease. Nutrients 2019, 11, 2358.

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