title: [Pharmacologic ascorbate treatment of influenza in vivo].
abstract: OBJECTIVE
  To investigate the effects of pharmacologic ascorbate (vitamin C) against Influenza A/CA/7/09 (H1N12009).
  
  
  METHODS
  BALB/c mice inoculated intranasally with influenza virus were treated with ascorbate (3 mg/g) twice daily by intraperitoneal (i.p.) injection for up to 14 d. Control groups received an equivalent volume of normal saline. Body weights were measured daily. To quantify the level of viral replication in the respiratory tract, the mice were euthanized and lungs removed and prepared as whole lung homogenates.Viral titers were determined by TCID50 assay in MDCK cells. Cytokine titers were determined by ELISA following the manufacturer's protocol (IL-1β, IL-6, TNF-α, IFN-α). For lung histopathologic evaluation, lungs were fixed with 10% neutral-buffered formalin at time of isolation, and then coded, processed into paraffin blocks, sectioned onto glass slides and stained (hematoxylin and eosin).Slides were examined and scored by a pathologist.
  
  
  RESULTS
  Mice infected with influenza virus and treated with pharmacologic ascorbate had higher survival and less weight loss, and had lung viral titers reduced by as much as 10 to 100-fold compared to the controls. Pathologic study of the lungs showed that the treated animals had little inflammation (bronchiolitis, perivasculitis, alveolitis, and vasculitis) compared to the controls.IL-1, IL-6, and IFN-alpha lung levels were lower in the treated animals compared to the controls.
  
  
  CONCLUSIONS
  Pharmacologic ascorbate is a pro-oxidant that eliminates influenza virus in the lung, and therefore reduces lung inflammation and lowers death rate in this mouse model.
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Linling
authors.initials: L
authors.lastname: Cheng
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007249:Inflammation; D009980:Influenza A virus; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D001205:Ascorbic Acid