title: Combination activity of neuraminidase inhibitor oseltamivir and α-tocopherol in influenza virus A (H3N2) infection in mice.
abstract: Influenza is a highly contagious viral infection of the respiratory system. To attack two processes involved in flu pathogenesis-viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza.
  
  
  
  After inoculation of albino mice with 10 MLD50 (50% mouse lethal dose) of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied orally at three doses, 2.5 mg/kg, 1.25 mg/kg, and 0.625 mg/kg, for five days post infection. α-Tocopherol (120 mg/kg, in sunflower oil) was administered intraperitoneally. Three schemes of α-tocopherol five-day course were tested: onset five or two days before infection, or on the virus inoculation day.
  
  
  
  Strongly dose-dependent augmented antiviral effect of the combination α-tocopherol and 0.625 mg/kg oseltamivir was demonstrated when α-tocopherol was administered simultaneously with oseltamivir: a pronounced decrease in mortality rate (a 78% protection), and a lengthening of mean survival time by 3.2-4 days. Lung parameters showed a substantial decrease in infectious virus content (Δ logs = 3.8/4.1) and a marked diminishment of lung index and pathology. Combination α-tocopherol with 1.25 mg/kg oseltamivir manifested a marked protective effect, but the effect on lung parameters was less. The combination effect of α-tocopherol with 2.5 mg/kg oseltamivir did not surpass the monotherapeutic effect of oseltamivir. When α-tocopherol was applied in courses starting five or two days before infection, its combination with oseltamivir was ineffective.
  
  
  
  Evidently, α-tocopherol could be considered as prospective component of influenza therapy in combination with oseltamivir.
authors.affiliation: The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria galabov@microbio.bas.bg.
authors.forename: Angel S
authors.initials: AS
authors.lastname: Galabov
authors.affiliation: The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Milka
authors.initials: M
authors.lastname: Mileva
authors.affiliation: The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Lora
authors.initials: L
authors.lastname: Simeonova
authors.affiliation: The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Galina
authors.initials: G
authors.lastname: Gegova
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D053139:Oseltamivir / Q000008:administration & dosage / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D024502:alpha-Tocopherol
keywords: Drug combination; animal model; infection; influenza; virus