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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Evidently, α-tocopherol could be considered as prospective component of influenza therapy in combination with oseltamivir.

• Authors: Angel S Galabov, Milka Mileva, Lora Simeonova, Galina Gegova
• Journal: Antiviral chemistry & chemotherapy (Antivir Chem Chemother) Vol. 24 Issue 3-4 Pg. 83-91 (08 2015) ISSN: 2040-2066 [Electronic] England
• PMID: 27341844 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2016.

Chemical References

• Enzyme Inhibitors
• Oseltamivir
• Neuraminidase
• alpha-Tocopherol

Topics

• Administration, Oral
• Animals
• Dogs
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Influenza A Virus, H3N2 Subtype (drug effects)
• Madin Darby Canine Kidney Cells (drug effects)
• Male
• Mice
• Mice, Inbred ICR
• Microbial Sensitivity Tests
• Neuraminidase (antagonists & inhibitors, metabolism)
• Orthomyxoviridae Infections (drug therapy)
• Oseltamivir (administration & dosage, pharmacology)
• Structure-Activity Relationship
• alpha-Tocopherol (administration & dosage, pharmacology)