title: Enhanced Resolution of Hyperoxic Acute Lung Injury as a result of Aspirin Triggered Resolvin D1 Treatment.
abstract: Acute lung injury (ALI), which presents as acute respiratory failure, is a major clinical problem that requires aggressive care, and patients who require prolonged oxygen exposure are at risk of developing this disease. Although molecular determinants of ALI have been reported, the molecules involved in disease catabasis associated with oxygen toxicity have not been well studied. It has been reported that lung mucosa is rich in omega-3 fatty acid dicosahexanoic acid (DHA), which has antiinflammatory properties. Aspirin-triggered resolvin D1 (AT-RvD1) is a potent proresolution metabolite of DHA that can curb the inflammatory effects in various acute injuries, yet the effect of AT-RvD1 on hyperoxic acute lung injury (HALI) or in the oxygen toxicity setting in general has not been investigated. The effects of AT-RvD1 on HALI were determined for the first time in 8- to 10-week-old C57BL/6 mice that were exposed to hyperoxia (≥95% O2) for 48 hours. Mice were given AT-RvD1 (100 ng) in saline or a saline vehicle for 24 hours in normoxic (≈21% O2) conditions after hyperoxia. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected for analysis associated with proinflammatory signaling and lung inflammation. AT-RvD1 treatment resulted in reduced oxidative stress, increased glutathione production, and significantly decreased tissue inflammation. AT-RvD1 treatment also significantly reduced the lung wet/dry ratio, protein in BAL fluid, and decreased apoptotic and NF-κB signaling. These results show that AT-RvD1 curbs oxygen-induced lung edema, permeability, inflammation, and apoptosis and is thus an effective therapy for prolonged hyperoxia exposure in this murine model.
authors: Departments of 1 Internal Medicine and.|2 Molecular Medicine, Division of Allergy and Immunology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors: Ruan
authors: R
authors: Cox
authors: Departments of 1 Internal Medicine and.
authors: Oluwakemi
authors: O
authors: Phillips
authors: Departments of 1 Internal Medicine and.
authors: Jutaro
authors: J
authors: Fukumoto
authors: Departments of 1 Internal Medicine and.
authors: Itsuko
authors: I
authors: Fukumoto
authors: Departments of 1 Internal Medicine and.
authors: Prasanna Tamarapu
authors: PT
authors: Parthasarathy
authors: Departments of 1 Internal Medicine and.
authors: Stephen
authors: S
authors: Arias
authors: Departments of 1 Internal Medicine and.
authors: Young
authors: Y
authors: Cho
authors: Departments of 1 Internal Medicine and.
authors: Richard F
authors: RF
authors: Lockey
authors: Departments of 1 Internal Medicine and.|2 Molecular Medicine, Division of Allergy and Immunology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors: Narasaiah
authors: N
authors: Kolliputi
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D000403:Airway Resistance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis; D001241:Aspirin / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D018496:Hyperoxia / Q000188:drug therapy* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D018384:Oxidative Stress
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D001241:Aspirin
keywords: acute lung injury; hyperoxia; resolvin
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