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

Yuki Enoki, Yu Ishima, Ryota Tanaka, Keizo Sato, Kazuhiko Kimachi, Tatsuya Shirai, Hiroshi Watanabe, Victor T.G. Chuang, Yukio Fujiwara, Motohiro Takeya, Masaki Otagiri, Toru Maruyama

Research output: Contribution to journalArticle

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Abstract

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-γ 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.

Original languageEnglish
Article numbere0130248
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - 2015 Jun 18
Externally publishedYes

Fingerprint

Levofloxacin
fluoroquinolones
Fluoroquinolones
Lung Injury
Orthomyxoviridae
Viruses
antibiotics
lungs
nitric oxide
Nitric Oxide
Anti-Bacterial Agents
Virus Diseases
reactive oxygen species
Reactive Oxygen Species
hydroxyl radicals
influenza
Hydroxyl Radical
Lung
Human Influenza
neutrophils

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Enoki, Y., Ishima, Y., Tanaka, R., Sato, K., Kimachi, K., Shirai, T., ... Maruyama, T. (2015). Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury. PLoS One, 10(6), [e0130248]. https://doi.org/10.1371/journal.pone.0130248

Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury. / Enoki, Yuki; Ishima, Yu; Tanaka, Ryota; Sato, Keizo; Kimachi, Kazuhiko; Shirai, Tatsuya; Watanabe, Hiroshi; Chuang, Victor T.G.; Fujiwara, Yukio; Takeya, Motohiro; Otagiri, Masaki; Maruyama, Toru.

In: PLoS One, Vol. 10, No. 6, e0130248, 18.06.2015.

Research output: Contribution to journalArticle

Enoki, Y, Ishima, Y, Tanaka, R, Sato, K, Kimachi, K, Shirai, T, Watanabe, H, Chuang, VTG, Fujiwara, Y, Takeya, M, Otagiri, M & Maruyama, T 2015, 'Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury', PLoS One, vol. 10, no. 6, e0130248. https://doi.org/10.1371/journal.pone.0130248
Enoki, Yuki ; Ishima, Yu ; Tanaka, Ryota ; Sato, Keizo ; Kimachi, Kazuhiko ; Shirai, Tatsuya ; Watanabe, Hiroshi ; Chuang, Victor T.G. ; Fujiwara, Yukio ; Takeya, Motohiro ; Otagiri, Masaki ; Maruyama, Toru. / Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury. In: PLoS One. 2015 ; Vol. 10, No. 6.
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