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Oral delivery of xenon for cardiovascular protection

Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an...

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Autores principales: Yin, Xing, Moody, Melanie R., Hebert, Valeria, Klegerman, Melvin E., Geng, Yong-Jian, Dugas, Tammy R., McPherson, David D., Kim, Hyunggun, Huang, Shao-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773773/
https://www.ncbi.nlm.nih.gov/pubmed/31575906
http://dx.doi.org/10.1038/s41598-019-50515-3
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author Yin, Xing
Moody, Melanie R.
Hebert, Valeria
Klegerman, Melvin E.
Geng, Yong-Jian
Dugas, Tammy R.
McPherson, David D.
Kim, Hyunggun
Huang, Shao-Ling
author_facet Yin, Xing
Moody, Melanie R.
Hebert, Valeria
Klegerman, Melvin E.
Geng, Yong-Jian
Dugas, Tammy R.
McPherson, David D.
Kim, Hyunggun
Huang, Shao-Ling
author_sort Yin, Xing
collection PubMed
description Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an orally deliverable, effective Xe formulation for long-term administration. We employed 2-hydroxypropyl)-β-cyclodextrin (HPCD), which was dissolved in water to increase the Xe concentration in solution. The beneficial effects of long-term oral administration of Xe-enriched solutions on cardiovascular function were evaluated in vivo. HPCD increased Xe solubility from 0.22 mM to 0.67 mM (3.8-fold). Aged ApoE knockout mice fed high-fat diet for 6 weeks developed hypertension, and myocardial hypertrophy with impaired cardiac function. Oral Xe prevented this ischemic damage, preserving normal blood pressure, while maintaining normal left ventricular mass and wall thickness. This novel formulation allows for gastrointestinal delivery and cardiovascular stabilization.
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spelling pubmed-67737732019-10-04 Oral delivery of xenon for cardiovascular protection Yin, Xing Moody, Melanie R. Hebert, Valeria Klegerman, Melvin E. Geng, Yong-Jian Dugas, Tammy R. McPherson, David D. Kim, Hyunggun Huang, Shao-Ling Sci Rep Article Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an orally deliverable, effective Xe formulation for long-term administration. We employed 2-hydroxypropyl)-β-cyclodextrin (HPCD), which was dissolved in water to increase the Xe concentration in solution. The beneficial effects of long-term oral administration of Xe-enriched solutions on cardiovascular function were evaluated in vivo. HPCD increased Xe solubility from 0.22 mM to 0.67 mM (3.8-fold). Aged ApoE knockout mice fed high-fat diet for 6 weeks developed hypertension, and myocardial hypertrophy with impaired cardiac function. Oral Xe prevented this ischemic damage, preserving normal blood pressure, while maintaining normal left ventricular mass and wall thickness. This novel formulation allows for gastrointestinal delivery and cardiovascular stabilization. Nature Publishing Group UK 2019-10-01 /pmc/articles/PMC6773773/ /pubmed/31575906 http://dx.doi.org/10.1038/s41598-019-50515-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yin, Xing
Moody, Melanie R.
Hebert, Valeria
Klegerman, Melvin E.
Geng, Yong-Jian
Dugas, Tammy R.
McPherson, David D.
Kim, Hyunggun
Huang, Shao-Ling
Oral delivery of xenon for cardiovascular protection
title Oral delivery of xenon for cardiovascular protection
title_full Oral delivery of xenon for cardiovascular protection
title_fullStr Oral delivery of xenon for cardiovascular protection
title_full_unstemmed Oral delivery of xenon for cardiovascular protection
title_short Oral delivery of xenon for cardiovascular protection
title_sort oral delivery of xenon for cardiovascular protection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773773/
https://www.ncbi.nlm.nih.gov/pubmed/31575906
http://dx.doi.org/10.1038/s41598-019-50515-3
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