Ascorbic Acid Attenuates Hyperoxia-Compromised Host Defense against Pulmonary Bacterial Infection.
Supraphysiological concentrations of oxygen (hyperoxia) can compromise host defense and increase susceptibility to bacterial infections, causing ventilator-associated pneumonia. The phagocytic activity of macrophages is impaired by hyperoxia-induced increases in the levels of reactive oxygen species (ROS) and extracellular high-mobility group box protein B1 (HMGB1). Ascorbic acid (AA), an essential nutrient and antioxidant, has been shown to be beneficial in various animal models of ROS-mediated diseases. The aim of this study was to determine whether AA could attenuate hyperoxia-compromised host defense and improve macrophage functions against bacterial infections. C57BL/6 male mice were exposed to hyperoxia (≥98% O2, 48 h), followed by intratracheal inoculation with Pseudomonas aeruginosa, and simultaneous intraperitoneal administration of AA. AA (50 mg/kg) significantly improved bacterial clearance in the lungs and airways, and significantly reduced HMGB1 accumulation in the airways. The incubation of RAW 264.7 cells (a macrophage-like cell line) with AA (0-1,000 μM) before hyperoxic exposure (95% O2) stabilized the phagocytic activity of macrophages in a concentration-dependent manner. The AA-enhanced macrophage function was associated with significantly decreased production of intracellular ROS and accumulation of extracellular HMGB1. These data suggest that AA supplementation can prevent or attenuate the development of ventilator-associated pneumonia in patients receiving oxygen support.
1 Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Health Sciences, Queens, New York.
Vivek S
http://orcid.org/0000-0001-8583-1548
VS
Patel
1 Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Health Sciences, Queens, New York.
Vaishali
V
Sampat
2 National Cancer Institute, Bethesda, Maryland.
Michael Graham
MG
Espey
1 Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Health Sciences, Queens, New York.
Ravikumar
http://orcid.org/0000-0003-2366-6254
R
Sitapara
3 The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York; and.
Haichao
H
Wang
1 Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Health Sciences, Queens, New York.
Xiaojing
X
Yang
1 Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Health Sciences, Queens, New York.
Charles R
CR
Ashby
4 Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois.
Douglas D
DD
Thomas
1 Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Health Sciences, Queens, New York.|3 The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York; and.
Lin L
LL
Mantell
ascorbic acid; high-mobility group box 1; hyperoxia; pneumonia