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Ascorbic Acid Attenuates Hyperoxia-Compromised Host Defense against Pulmonary Bacterial Infection
Vivek S Patel1, Vaishali Sampat1, Michael Graham Espey2
11 Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Health Sciences, Queens, New York.
Ascorbic acid (AA) enhances macrophage function and improves bacterial clearance during hyperoxia, offering a potential treatment for ventilator-associated pneumonia by reducing reactive oxygen species and HMGB1.
Area of Science:
- Pulmonary Medicine
- Immunology
- Nutritional Science
Background:
- Supraphysiological oxygen (hyperoxia) impairs macrophage phagocytosis via increased reactive oxygen species (ROS) and high-mobility group box protein B1 (HMGB1).
- This impairment increases susceptibility to bacterial infections like ventilator-associated pneumonia (VAP).
Purpose of the Study:
- To investigate if ascorbic acid (AA) can mitigate hyperoxia-induced host defense compromise.
- To determine AA's effect on macrophage function and bacterial infection during hyperoxia.
Main Methods:
- C57BL/6 mice exposed to hyperoxia (≥98% O2) and inoculated with Pseudomonas aeruginosa, with simultaneous AA administration.
- RAW 264.7 macrophage-like cells incubated with AA prior to hyperoxic exposure (95% O2).
Main Results:
- AA (50 mg/kg) significantly improved bacterial clearance and reduced airway HMGB1 in mice.
- AA stabilized macrophage phagocytic activity in a concentration-dependent manner.
- AA decreased intracellular ROS production and extracellular HMGB1 accumulation in macrophages.
Conclusions:
- Ascorbic acid supplementation can prevent or attenuate ventilator-associated pneumonia development.
- AA enhances macrophage function, offering a therapeutic strategy for hyperoxia-induced immune compromise.
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