Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2...

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Autores principales:	Alejandro Gonzaléz-Candia, Pamela V. Arias, Simón A. Aguilar, Esteban G. Figueroa, Roberto V. Reyes, Germán Ebensperger, Aníbal J. Llanos, Emilio A. Herrera
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	antioxidant enzymes pro-oxidant sources right ventricular remodeling pulmonary arterial hypertension of the neonate melatonin receptors Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/505e4c815cb54758b1ed2fffa5ecb88a
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spelling	oai:doaj.org-article:505e4c815cb54758b1ed2fffa5ecb88a2021-11-25T16:25:30ZMelatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia10.3390/antiox101116582076-3921https://doaj.org/article/505e4c815cb54758b1ed2fffa5ecb88a2021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1658https://doaj.org/toc/2076-3921Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia in lowlands. Still, pulmonary and cardiac impairments in PAHN lack effective treatments. Previously we have shown the beneficial effects of neonatal melatonin treatment on pulmonary circulation. However, the cardiac effects of this treatment are unknown. In this study, we assessed whether melatonin improves cardiac function and modulates right ventricle (RV) oxidative stress. Ten lambs were gestated, born, and raised at 3600 m. Lambs were divided in two groups. One received daily vehicle as control, and another received daily melatonin (1 mg·kg<sup>−1</sup>·d<sup>−1</sup>) for 21 days. Daily cardiovascular measurements were recorded and, at 29 days old, cardiac tissue was collected. Melatonin decreased pulmonary arterial pressure at the end of the experimental period. In addition, melatonin enhanced manganese superoxide dismutase and catalase (CAT) expression, while increasing CAT activity in RV. This was associated with a decrease in superoxide anion generation at the mitochondria and NADPH oxidases in RV. Finally, these effects were associated with a marked decrease of oxidative stress markers in RV. These findings support the cardioprotective effects of an oral administration of melatonin in newborns that suffer from developmental chronic hypoxia.Alejandro Gonzaléz-CandiaPamela V. AriasSimón A. AguilarEsteban G. FigueroaRoberto V. ReyesGermán EbenspergerAníbal J. LlanosEmilio A. HerreraMDPI AGarticleantioxidant enzymespro-oxidant sourcesright ventricular remodelingpulmonary arterial hypertension of the neonatemelatonin receptorsTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1658, p 1658 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antioxidant enzymes pro-oxidant sources right ventricular remodeling pulmonary arterial hypertension of the neonate melatonin receptors Therapeutics. Pharmacology RM1-950
spellingShingle	antioxidant enzymes pro-oxidant sources right ventricular remodeling pulmonary arterial hypertension of the neonate melatonin receptors Therapeutics. Pharmacology RM1-950 Alejandro Gonzaléz-Candia Pamela V. Arias Simón A. Aguilar Esteban G. Figueroa Roberto V. Reyes Germán Ebensperger Aníbal J. Llanos Emilio A. Herrera Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia
description	Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia in lowlands. Still, pulmonary and cardiac impairments in PAHN lack effective treatments. Previously we have shown the beneficial effects of neonatal melatonin treatment on pulmonary circulation. However, the cardiac effects of this treatment are unknown. In this study, we assessed whether melatonin improves cardiac function and modulates right ventricle (RV) oxidative stress. Ten lambs were gestated, born, and raised at 3600 m. Lambs were divided in two groups. One received daily vehicle as control, and another received daily melatonin (1 mg·kg<sup>−1</sup>·d<sup>−1</sup>) for 21 days. Daily cardiovascular measurements were recorded and, at 29 days old, cardiac tissue was collected. Melatonin decreased pulmonary arterial pressure at the end of the experimental period. In addition, melatonin enhanced manganese superoxide dismutase and catalase (CAT) expression, while increasing CAT activity in RV. This was associated with a decrease in superoxide anion generation at the mitochondria and NADPH oxidases in RV. Finally, these effects were associated with a marked decrease of oxidative stress markers in RV. These findings support the cardioprotective effects of an oral administration of melatonin in newborns that suffer from developmental chronic hypoxia.
format	article
author	Alejandro Gonzaléz-Candia Pamela V. Arias Simón A. Aguilar Esteban G. Figueroa Roberto V. Reyes Germán Ebensperger Aníbal J. Llanos Emilio A. Herrera
author_facet	Alejandro Gonzaléz-Candia Pamela V. Arias Simón A. Aguilar Esteban G. Figueroa Roberto V. Reyes Germán Ebensperger Aníbal J. Llanos Emilio A. Herrera
author_sort	Alejandro Gonzaléz-Candia
title	Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia
title_short	Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia
title_full	Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia
title_fullStr	Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia
title_full_unstemmed	Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia
title_sort	melatonin reduces oxidative stress in the right ventricle of newborn sheep gestated under chronic hypoxia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/505e4c815cb54758b1ed2fffa5ecb88a
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Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

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