Oseltamivir and S-Adenosyl-L-Methionine Combination as Effective
                    Therapeutic Strategy for Suppression of Oxidative Damage in Lung Caused by
                    Influenza Virus Infection in Mice

Milka Mileva; Adriana Dimitrova; Dimo Krastev; Albena Alexandrova; Elina Tsvetanova; Almira Georgieva; Angel Galabov

doi:10.1055/a-1147-8824

Drug Research, Table of Contents

Drug Res (Stuttg) 2020; 70(06): 273-279
DOI: 10.1055/a-1147-8824

Original Article

Oseltamivir and S-Adenosyl-L-Methionine Combination as Effective Therapeutic Strategy for Suppression of Oxidative Damage in Lung Caused by Influenza Virus Infection in Mice

Milka Mileva

¹The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria

,

Adriana Dimitrova

¹The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria

,

Dimo Krastev

²Medical University of Sofia, Medical College, Sofia, Bulgaria

,

Albena Alexandrova

³Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria

,

Elina Tsvetanova

³Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria

,

Almira Georgieva

³Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria

,

Angel Galabov

¹The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria

› Author Affiliations

Abstract

Background and objectives The pathogenesis of influenza infection is associated with two general processes in the body: (a) lung damage based on virus replication; (b) overproduction of free radicals, antioxidant deficiency, and development of oxidative stress. To attack these aspects of flu pathogenesis, we explored the combined effect of the antiviral agent oseltamivir, and s-adenosyl-l-methionine (SAM) as a precursor of the endogenous antioxidant glutathione, in mice infected with influenza virus.

Methods After inoculation of albino mice with 10 MLD₅₀ of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied twice a day, for five days post-infection in doses of 1.25 and 2.5 mg/kg. SAM was administered once a day for 10 days, starting 5 days before infection in doses of 50, 100 and 150 mg/kg.

Results Monotherapy with SAM did not influence the markers of oxidative stress in the lung. Combination of SAM 50 mg/kg and oseltamivir 2.5 mg/kg affected best the virological parameters - viral titer, protection index, and mean survival time, as well as the biochemical markers of oxidative stress.

Interpretation and conclusions Combining of SAM and oseltamivir in a dose of 1/4 of optimal therapeutic could be considered as a perspective therapy of influenza viral infection.

Key words:

influenza infection - oxidative stress - antioxidant - glutathione

Full Text

References

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