Molchanova, AY;
Rjabceva, SN;
Melik-Kasumov, TB;
Pestov, NB;
Angelova, PR;
Shmanai, VV;
Sharko, OL;
... Shchepinov, MS; + view all
(2022)
Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice.
Antioxidants
, 11
(4)
, Article 681. 10.3390/antiox11040681.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/antiox11040681 |
| Publisher version: | https://doi.org/10.3390/antiox11040681 |
| Language: | English |
| Additional information: | © 2022 MDPI. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | lung; acute respiratory distress syndrome; arachidonic acid; D-PUFA; eicosanoids; isotope effect |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10147520 |
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