Combination Activity of Neuraminidase Inhibitor Oseltamivir and α-tocopherol in Influenza Virus A (H3N2) Infection in Mice

Overview

Journal Antivir Chem Chemother

Publisher Sage Publications

Specialties Chemistry
Infectious Diseases
Microbiology

Date 2016 Jun 26

PMID 27341844

Citations 8

Authors

Angel S Galabov

Milka Mileva

Lora Simeonova

Galina Gegova

Affiliations

Soon will be listed here.

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.

Citing Articles

In Vitro Anti-Influenza Virus Activity of Non-Polar subsp. Extract.

Eliopoulos A, Angelis A, Liakakou A, Skaltsounis L Pharmaceuticals (Basel). 2022; 15(12).

PMID: 36558964 PMC: 9787935. DOI: 10.3390/ph15121513.

Fetal Brain Damage during Maternal COVID-19: Emerging Hypothesis, Mechanism, and Possible Mitigation through Maternal-Targeted Nutritional Supplementation.

Germano C, Messina A, Tavella E, Vitale R, Avellis V, Barboni M Nutrients. 2022; 14(16).

PMID: 36014809 PMC: 9414753. DOI: 10.3390/nu14163303.

Micronutrients, Phytochemicals and Mediterranean Diet: A Potential Protective Role against COVID-19 through Modulation of PAF Actions and Metabolism.

Detopoulou P, Demopoulos C, Antonopoulou S Nutrients. 2021; 13(2).

PMID: 33573169 PMC: 7911163. DOI: 10.3390/nu13020462.

SARS-CoV-2 and Other Respiratory Viruses: What Does Oxidative Stress Have to Do with It?.

Fernandes I, de Brito C, Dos Reis V, Sato M, Pereira N Oxid Med Cell Longev. 2020; 2020:8844280.

PMID: 33381273 PMC: 7757116. DOI: 10.1155/2020/8844280.

Redox-Modulating Agents in the Treatment of Viral Infections.

Checconi P, De Angelis M, Marcocci M, Fraternale A, Magnani M, Palamara A Int J Mol Sci. 2020; 21(11).

PMID: 32521619 PMC: 7312898. DOI: 10.3390/ijms21114084.

References

Meydani S, Barklund M, Liu S, Meydani M, Miller R, Cannon J . Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr. 1990; 52(3):557-63. DOI: 10.1093/ajcn/52.3.557. View

Berri F, Rimmelzwaan G, Hanss M, Albina E, Foucault-Grunenwald M, Le V . Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis. PLoS Pathog. 2013; 9(3):e1003229. PMC: 3605290. DOI: 10.1371/journal.ppat.1003229. View

Papic N, Pangercic A, Vargovic M, Barsic B, Vince A, Kuzman I . Liver involvement during influenza infection: perspective on the 2009 influenza pandemic. Influenza Other Respir Viruses. 2011; 6(3):e2-5. PMC: 4941665. DOI: 10.1111/j.1750-2659.2011.00287.x. View

Taubenberger J, Morens D . The pathology of influenza virus infections. Annu Rev Pathol. 2007; 3:499-522. PMC: 2504709. DOI: 10.1146/annurev.pathmechdis.3.121806.154316. View

Khoufache K, Berri F, Nacken W, Vogel A, Delenne M, Camerer E . PAR1 contributes to influenza A virus pathogenicity in mice. J Clin Invest. 2012; 123(1):206-14. PMC: 3533265. DOI: 10.1172/JCI61667. View

Nencioni L, Sgarbanti R, Amatore D, Checconi P, Celestino I, Limongi D . Intracellular redox signaling as therapeutic target for novel antiviral strategy. Curr Pharm Des. 2011; 17(35):3898-904. DOI: 10.2174/138161211798357728. View

Kaneko K, Kiyose C, Ueda T, Ichikawa H, Igarashi O . Studies of the metabolism of alpha-tocopherol stereoisomers in rats using [5-methyl-(14)C]SRR- and RRR-alpha-tocopherol. J Lipid Res. 2000; 41(3):357-67. View

Short K, Diavatopoulos D, Thornton R, Pedersen J, Strugnell R, Wise A . Influenza virus induces bacterial and nonbacterial otitis media. J Infect Dis. 2011; 204(12):1857-65. PMC: 3209809. DOI: 10.1093/infdis/jir618. View

Brydon E, Morris S, Sweet C . Role of apoptosis and cytokines in influenza virus morbidity. FEMS Microbiol Rev. 2005; 29(4):837-50. DOI: 10.1016/j.femsre.2004.12.003. View

10.

Hayek M, Taylor S, Bender B, Han S, Meydani M, Smith D . Vitamin E supplementation decreases lung virus titers in mice infected with influenza. J Infect Dis. 1997; 176(1):273-6. DOI: 10.1086/517265. View

11.

Kagan V . Tocopherol stabilizes membrane against phospholipase A, free fatty acids, and lysophospholipids. Ann N Y Acad Sci. 1989; 570:121-35. DOI: 10.1111/j.1749-6632.1989.tb14913.x. View

12.

Kumar P, Khanna M, Srivastava V, Tyagi Y, Raj H, Ravi K . Effect of quercetin supplementation on lung antioxidants after experimental influenza virus infection. Exp Lung Res. 2005; 31(5):449-59. DOI: 10.1080/019021490927088. View

13.

Wang X, Quinn P . Vitamin E and its function in membranes. Prog Lipid Res. 2000; 38(4):309-36. DOI: 10.1016/s0163-7827(99)00008-9. View

14.

Kuiken T, Riteau B, Fouchier R, Rimmelzwaan G . Pathogenesis of influenza virus infections: the good, the bad and the ugly. Curr Opin Virol. 2012; 2(3):276-86. DOI: 10.1016/j.coviro.2012.02.013. View

15.

Hasani-Ranjbar S, Larijani B, Abdollahi M . A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Inflamm Allergy Drug Targets. 2009; 8(1):2-10. DOI: 10.2174/187152809787582561. View

16.

Tolle A, Schlame M, Charlier N, Guthmann F, Rustow B . Vitamin E differentially regulates the expression of peroxiredoxin-1 and -6 in alveolar type II cells. Free Radic Biol Med. 2005; 38(10):1401-8. DOI: 10.1016/j.freeradbiomed.2005.02.001. View

17.

Han S, Meydani S . Antioxidants, cytokines, and influenza infection in aged mice and elderly humans. J Infect Dis. 2000; 182 Suppl 1:S74-80. DOI: 10.1086/315915. View

18.

Ohkura T, Momose F, Ichikawa R, Takeuchi K, Morikawa Y . Influenza A virus hemagglutinin and neuraminidase mutually accelerate their apical targeting through clustering of lipid rafts. J Virol. 2014; 88(17):10039-55. PMC: 4136309. DOI: 10.1128/JVI.00586-14. View

19.

Niki E, Traber M . A history of vitamin E. Ann Nutr Metab. 2012; 61(3):207-12. DOI: 10.1159/000343106. View

20.

Le V, Schneider J, Boergeling Y, Berri F, Ducatez M, Guerin J . Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis. Am J Respir Crit Care Med. 2015; 191(7):804-19. DOI: 10.1164/rccm.201406-1031OC. View