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Open AccessArticle

Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1

1
Department of Pharmaceutical Sciences, College of Pharmacy, St. John’s University Queens, Queens, NY 11439, USA
2
National Cancer Institute, Bethesda, MD 20892-9747, USA
3
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA
4
The Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY 11030, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(3), 977; https://doi.org/10.3390/ijms21030977
Received: 2 December 2019 / Revised: 26 January 2020 / Accepted: 28 January 2020 / Published: 1 February 2020
Mechanical ventilation with hyperoxia is the major supportive measure to treat patients with acute lung injury and acute respiratory distress syndrome (ARDS). However, prolonged exposure to hyperoxia can induce oxidative inflammatory lung injury. Previously, we have shown that high levels of airway high-mobility group box 1 protein (HMGB1) mediate hyperoxia-induced acute lung injury (HALI). Using both ascorbic acid (AA, also known as vitamin C) and sulforaphane (SFN), an inducer of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), we tested the hypothesis that dietary antioxidants can mitigate HALI by ameliorating HMGB1-compromised macrophage function in phagocytosis by attenuating hyperoxia-induced extracellular HMGB1 accumulation. Our results indicated that SFN, which has been shown to attenute HALI in mice exposed to hyperoxia, dose-dependently restored hyperoxia-compromised macrophage function in phagocytosis (75.9 ± 3.5% in 0.33 µM SFN versus 50.7 ± 1.8% in dimethyl sulfoxide (DMSO) control, p < 0.05) by reducing oxidative stress and HMGB1 release from cultured macrophages (47.7 ± 14.7% in 0.33 µM SFN versus 93.1 ± 14.6% in DMSO control, p < 0.05). Previously, we have shown that AA enhances hyperoxic macrophage functions by reducing hyperoxia-induced HMGB1 release. Using a mouse model of HALI, we determined the effects of AA on hyperoxia-induced inflammatory lung injury. The i.p. administration of 50 mg/kg of AA to mice exposed to 72 h of ≥98% O2 significantly decreased hyperoxia-induced oxidative and nitrosative stress in mouse lungs. There was a significant decrease in the levels of airway HMGB1 (43.3 ± 12.2% in 50 mg/kg AA versus 96.7 ± 9.39% in hyperoxic control, p < 0.05), leukocyte infiltration (60.39 ± 4.137% leukocytes numbers in 50 mg/kg AA versus 100 ± 5.82% in hyperoxic control, p < 0.05) and improved lung integrity in mice treated with AA. Our study is the first to report that the dietary antioxidants, ascorbic acid and sulforaphane, ameliorate HALI and attenuate hyperoxia-induced macrophage dysfunction through an HMGB1-mediated pathway. Thus, dietary antioxidants could be used as potential treatments for oxidative-stress-induced acute inflammatory lung injury in patients receiving mechanical ventilation. View Full-Text
Keywords: ascorbic acid; sulforaphane; HALI; ARDS; HMGB1; Nrf2; dietary antioxidants; macrophages; oxidative stress; phagocytosis ascorbic acid; sulforaphane; HALI; ARDS; HMGB1; Nrf2; dietary antioxidants; macrophages; oxidative stress; phagocytosis
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MDPI and ACS Style

Patel, V.; Dial, K.; Wu, J.; Gauthier, A.G.; Wu, W.; Lin, M.; Espey, M.G.; Thomas, D.D.; Ashby, C.R., Jr.; Mantell, L.L. Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1. Int. J. Mol. Sci. 2020, 21, 977. https://doi.org/10.3390/ijms21030977

AMA Style

Patel V, Dial K, Wu J, Gauthier AG, Wu W, Lin M, Espey MG, Thomas DD, Ashby CR Jr., Mantell LL. Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1. International Journal of Molecular Sciences. 2020; 21(3):977. https://doi.org/10.3390/ijms21030977

Chicago/Turabian Style

Patel, Vivek; Dial, Katelyn; Wu, Jiaqi; Gauthier, Alex G.; Wu, Wenjun; Lin, Mosi; Espey, Michael G.; Thomas, Douglas D.; Ashby, Charles R., Jr.; Mantell, Lin L. 2020. "Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1" Int. J. Mol. Sci. 21, no. 3: 977. https://doi.org/10.3390/ijms21030977

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