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    Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury

    234556_234556.pdf (1.374Mb)
    Access Status
    Open access
    Authors
    Enoki, Y.
    Ishima, Y.
    Tanaka, R.
    Sato, K.
    Kimachi, K.
    Shirai, T.
    Watanabe, H.
    Chuang, Victor
    Fujiwara, Y.
    Takeya, M.
    Otagiri, Masaki
    Maruyama, T.
    Date
    2015
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Enoki, Y. and Ishima, Y. and Tanaka, R. and Sato, K. and Kimachi, K. and Shirai, T. and Watanabe, H. et al. 2015. Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury. PLoS ONE. 10 (6): e0130248.
    Source Title
    PLoS ONE
    DOI
    10.1371/journal.pone.0130248
    School
    School of Pharmacy
    Remarks

    This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by/4.0/

    URI
    http://hdl.handle.net/20.500.11937/39747
    Collection
    • Curtin Research Publications
    Abstract

    © 2015 Enoki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-? in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs.

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