Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice

Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enh...

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Autores principales:	Genís Campreciós, Maria Ruart, Aina Anton, Nuria Suárez-Herrera, Carla Montironi, Celia Martínez, Natalia Jiménez, Erica Lafoz, Héctor García-Calderó, Marina Vilaseca, Marta Magaz, Mar Coll, Isabel Graupera, Scott L. Friedman, Joan Carles García-Pagán, Virginia Hernández-Gea
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autophagy mitophagy LSEC endothelial dysfunction liver fibrosis Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/1294761bd9f54395846543f08d3de8ef
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spelling	oai:doaj.org-article:1294761bd9f54395846543f08d3de8ef2021-11-25T18:33:17ZSpermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice10.3390/nu131137002072-6643https://doaj.org/article/1294761bd9f54395846543f08d3de8ef2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/3700https://doaj.org/toc/2072-6643Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans. We evaluated the use of dietary supplementation with SPD in two models of liver disease (CCl<sub>4</sub> and CDAAH diet). We analyzed the effect of SPD on endothelial dysfunction in vitro and in vivo. C57BL/6J mice were supplemented with SPD in the drinking water prior and concomitantly with CCl<sub>4</sub> and CDAAH treatments. Endothelial autophagy deficient (Atg7endo) mice were also evaluated. Liver tissue was used to evaluate the impact of SPD prophylaxis on liver damage, endothelial dysfunction, oxidative stress, mitochondrial status, inflammation and liver fibrosis. SPD improved the endothelial response to oxidative injury in vitro and improved the liver endothelial phenotype and protected against liver injury in vivo. SPD reduced the overall liver oxidative stress and improved mitochondrial fitness. The absence of benefits in the Atg7endo mice suggests an autophagy-dependent effect of SPD. This study suggests SPD diet supplementation in early phases of disease protects the liver endothelium from oxidative stress and may be an attractive approach to modify the chronic liver disease course and halt fibrosis progression.Genís CampreciósMaria RuartAina AntonNuria Suárez-HerreraCarla MontironiCelia MartínezNatalia JiménezErica LafozHéctor García-CalderóMarina VilasecaMarta MagazMar CollIsabel GrauperaScott L. FriedmanJoan Carles García-PagánVirginia Hernández-GeaMDPI AGarticleautophagymitophagyLSECendothelial dysfunctionliver fibrosisNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 3700, p 3700 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy mitophagy LSEC endothelial dysfunction liver fibrosis Nutrition. Foods and food supply TX341-641
spellingShingle	autophagy mitophagy LSEC endothelial dysfunction liver fibrosis Nutrition. Foods and food supply TX341-641 Genís Campreciós Maria Ruart Aina Anton Nuria Suárez-Herrera Carla Montironi Celia Martínez Natalia Jiménez Erica Lafoz Héctor García-Calderó Marina Vilaseca Marta Magaz Mar Coll Isabel Graupera Scott L. Friedman Joan Carles García-Pagán Virginia Hernández-Gea Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
description	Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans. We evaluated the use of dietary supplementation with SPD in two models of liver disease (CCl<sub>4</sub> and CDAAH diet). We analyzed the effect of SPD on endothelial dysfunction in vitro and in vivo. C57BL/6J mice were supplemented with SPD in the drinking water prior and concomitantly with CCl<sub>4</sub> and CDAAH treatments. Endothelial autophagy deficient (Atg7endo) mice were also evaluated. Liver tissue was used to evaluate the impact of SPD prophylaxis on liver damage, endothelial dysfunction, oxidative stress, mitochondrial status, inflammation and liver fibrosis. SPD improved the endothelial response to oxidative injury in vitro and improved the liver endothelial phenotype and protected against liver injury in vivo. SPD reduced the overall liver oxidative stress and improved mitochondrial fitness. The absence of benefits in the Atg7endo mice suggests an autophagy-dependent effect of SPD. This study suggests SPD diet supplementation in early phases of disease protects the liver endothelium from oxidative stress and may be an attractive approach to modify the chronic liver disease course and halt fibrosis progression.
format	article
author	Genís Campreciós Maria Ruart Aina Anton Nuria Suárez-Herrera Carla Montironi Celia Martínez Natalia Jiménez Erica Lafoz Héctor García-Calderó Marina Vilaseca Marta Magaz Mar Coll Isabel Graupera Scott L. Friedman Joan Carles García-Pagán Virginia Hernández-Gea
author_facet	Genís Campreciós Maria Ruart Aina Anton Nuria Suárez-Herrera Carla Montironi Celia Martínez Natalia Jiménez Erica Lafoz Héctor García-Calderó Marina Vilaseca Marta Magaz Mar Coll Isabel Graupera Scott L. Friedman Joan Carles García-Pagán Virginia Hernández-Gea
author_sort	Genís Campreciós
title	Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
title_short	Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
title_full	Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
title_fullStr	Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
title_full_unstemmed	Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
title_sort	spermidine supplementation protects the liver endothelium from liver damage in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1294761bd9f54395846543f08d3de8ef
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Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice

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