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Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice

Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at bis-ally...

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Autores principales: Molchanova, Alla Y., Rjabceva, Svetlana N., Melik-Kasumov, Tigran B., Pestov, Nikolay B., Angelova, Plamena R., Shmanai, Vadim V., Sharko, Olga L., Bekish, Andrei V., James, Genevieve, Park, Hui Gyu, Udalova, Irina A., Brenna, J. Thomas, Shchepinov, Mikhail S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027010/
https://www.ncbi.nlm.nih.gov/pubmed/35453366
http://dx.doi.org/10.3390/antiox11040681
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author Molchanova, Alla Y.
Rjabceva, Svetlana N.
Melik-Kasumov, Tigran B.
Pestov, Nikolay B.
Angelova, Plamena R.
Shmanai, Vadim V.
Sharko, Olga L.
Bekish, Andrei V.
James, Genevieve
Park, Hui Gyu
Udalova, Irina A.
Brenna, J. Thomas
Shchepinov, Mikhail S.
author_facet Molchanova, Alla Y.
Rjabceva, Svetlana N.
Melik-Kasumov, Tigran B.
Pestov, Nikolay B.
Angelova, Plamena R.
Shmanai, Vadim V.
Sharko, Olga L.
Bekish, Andrei V.
James, Genevieve
Park, Hui Gyu
Udalova, Irina A.
Brenna, J. Thomas
Shchepinov, Mikhail S.
author_sort Molchanova, Alla Y.
collection PubMed
description Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at bis-allylic positions substantially decreases the overall rate of ARA oxidation when hydrogen abstraction is an initiating event. To compare the effects of dosing of arachidonic acid (H-ARA) and its bis-allylic hexadeuterated form (D-ARA) on lungs in conventionally healthy mice and in an acute lung injury model, mice were dosed with H-ARA or D-ARA for six weeks through dietary supplementation and then challenged with intranasal lipopolysaccharide (LPS) for subsequent analysis of bronchoalveolar lavage fluid and lung tissue. Dosing on D-ARA resulted in successful incorporation of D-ARA into various tissues. D-ARA significantly reduced LPS-induced adverse effects on alveolar septal thickness and the bronchoalveolar area. Oral deuterated ARA is taken up efficiently and protects against adverse LPS-induced pathology. This suggests novel therapeutic avenues for reducing lung damage during severe infections and other pathological conditions with inflammation in the pulmonary system and other inflammatory diseases.
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spelling pubmed-90270102022-04-23 Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice Molchanova, Alla Y. Rjabceva, Svetlana N. Melik-Kasumov, Tigran B. Pestov, Nikolay B. Angelova, Plamena R. Shmanai, Vadim V. Sharko, Olga L. Bekish, Andrei V. James, Genevieve Park, Hui Gyu Udalova, Irina A. Brenna, J. Thomas Shchepinov, Mikhail S. Antioxidants (Basel) Article Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at bis-allylic positions substantially decreases the overall rate of ARA oxidation when hydrogen abstraction is an initiating event. To compare the effects of dosing of arachidonic acid (H-ARA) and its bis-allylic hexadeuterated form (D-ARA) on lungs in conventionally healthy mice and in an acute lung injury model, mice were dosed with H-ARA or D-ARA for six weeks through dietary supplementation and then challenged with intranasal lipopolysaccharide (LPS) for subsequent analysis of bronchoalveolar lavage fluid and lung tissue. Dosing on D-ARA resulted in successful incorporation of D-ARA into various tissues. D-ARA significantly reduced LPS-induced adverse effects on alveolar septal thickness and the bronchoalveolar area. Oral deuterated ARA is taken up efficiently and protects against adverse LPS-induced pathology. This suggests novel therapeutic avenues for reducing lung damage during severe infections and other pathological conditions with inflammation in the pulmonary system and other inflammatory diseases. MDPI 2022-03-31 /pmc/articles/PMC9027010/ /pubmed/35453366 http://dx.doi.org/10.3390/antiox11040681 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Molchanova, Alla Y.
Rjabceva, Svetlana N.
Melik-Kasumov, Tigran B.
Pestov, Nikolay B.
Angelova, Plamena R.
Shmanai, Vadim V.
Sharko, Olga L.
Bekish, Andrei V.
James, Genevieve
Park, Hui Gyu
Udalova, Irina A.
Brenna, J. Thomas
Shchepinov, Mikhail S.
Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
title Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
title_full Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
title_fullStr Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
title_full_unstemmed Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
title_short Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
title_sort deuterated arachidonic acid ameliorates lipopolysaccharide-induced lung damage in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027010/
https://www.ncbi.nlm.nih.gov/pubmed/35453366
http://dx.doi.org/10.3390/antiox11040681
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