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Combination activity of neuraminidase inhibitor oseltamivir and α-tocopherol in influenza virus A (H3N2) infection in mice

tetano

Editor, Senior Moderator
Antivir Chem Chemother. 2016 Jun 24. pii: 2040206616656263. [Epub ahead of print]
[h=1]Combination activity of neuraminidase inhibitor oseltamivir and α-tocopherol in influenza virus A (H3N2) infection in mice.[/h] Galabov AS[SUP]1[/SUP], Mileva M[SUP]2[/SUP], Simeonova L[SUP]2[/SUP], Gegova G[SUP]2[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] Evidently, α-tocopherol could be considered as prospective component of influenza therapy in combination with oseltamivir.
? The Author(s) 2016.


[h=4]KEYWORDS:[/h] Drug combination; animal model; infection; influenza; virus

PMID: 27341844 DOI: 10.1177/2040206616656263
[PubMed - as supplied by publisher]
 
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