Chest Infections: Chest Infections |

Pharmacologic Ascorbate Treatment of Influenza A In Vitro and In Vivo in Mice FREE TO VIEW

Linling Cheng, MD
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Guangzhou Institute of Respiratory Disease, Guangzhou, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A83. doi:10.1016/j.chest.2016.02.088
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SESSION TITLE: Chest Infections

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: The possibility exists for an influenza pandemic, and new treatments are needed. We postulated that hydrogen peroxide generated by pharmacologic vitamin C had antiviral properties.

METHODS: Ascorbate was analyzed with HPLC and H2O2 was measured by Clark electrode. NHBE cells infected with virus were treated with ascorbic acid, then harvested to determine virus titer. BALB/c mice infected intranasally with influenza virus were treatments with ascorbic acid, and lung were havested for viral titration and histopathologic evaluation

RESULTS: Pharmacologic ascorbate (vitamin C) is a pro-drug that produces detectable steady-state concentrations of hydrogen peroxide (H2O2) in extracellular fluid but not blood. At concentrations that are safely and easily achievable in humans, pharmacologic ascorbate reduced or eliminated infectivity of influenza A viruses H3N2, H1N12009, and H1N12009 oseltamivir-resistant in vitro, effects mediated by H2O2. In vivo, pharmacologic but not oral ascorbate treatment reduced lung viral titers in infected mice 10-100 fold, and prevented weight loss and death. Microscopic examination of lung from infected animals, with blinded evaluation, revealed normal or nearly normal tissues from treated animals, compared to unambiguous inflammatory changes in controls. Pharmacologic ascorbate is a promising new treatment agent for influenza and deserves clinical exploration.

CONCLUSIONS: Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of virus in vitro and in vivo. Our in vitro studies show the antiviral effect of ascorbic acid appeared to be dose-dependent and 20mM ascorbic acid can totally block viral replication in vitro. In vivo experiments show pharmacological ascorbic acid can reduce at least 1 log of virus titer in lung and ascorbic acid take maximum anti-viral effects at early and middle treatment of virus disease.

CLINICAL IMPLICATIONS: Pharmacologic ascorbate is a promising new treatment agent for influenza and deserves clinical exploration.

DISCLOSURE: The following authors have nothing to disclose: Linling Cheng

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