Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
Autor: | Alla Y. Molchanova, Svetlana N. Rjabceva, Tigran B. Melik-Kasumov, Nikolay B. Pestov, Plamena R. Angelova, Vadim V. Shmanai, Olga L. Sharko, Andrei V. Bekish, Genevieve James, Hui Gyu Park, Irina A. Udalova, J. Thomas Brenna, Mikhail S. Shchepinov |
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Rok vydání: | 2021 |
Předmět: |
carbohydrates (lipids)
lung acute respiratory distress syndrome arachidonic acid D-PUFA eicosanoids isotope effect Physiology Clinical Biochemistry food and beverages heterocyclic compounds lipids (amino acids peptides and proteins) Cell Biology biochemical phenomena metabolism and nutrition Molecular Biology Biochemistry |
Zdroj: | Antioxidants; Volume 11; Issue 4; Pages: 681 |
ISSN: | 2076-3921 |
Popis: | 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. |
Databáze: | OpenAIRE |
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