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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
1   The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
,
Adriana Dimitrova
1   The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
,
Dimo Krastev
2   Medical University of Sofia, Medical College, Sofia, Bulgaria
,
Albena Alexandrova
3   Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
,
Elina Tsvetanova
3   Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
,
Almira Georgieva
3   Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
,
Angel Galabov
1   The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
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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


Publication History

Received: 12 February 2020

Accepted: 25 March 2020

Article published online:
21 April 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

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