Preliminary investigation on the combined effect of S-adenosyl-L-methionine (SAM) and oseltamivir on experimental influenza А virus infection in mice

Abstract

Influenza is one of the most contageous viral diseases, caused by influenza virus and affects thousands of people every year. The infection causes changes in the intracellular redox balance, increased production of reactive oxygen species, development of antioxidant  deficiency and conditions of oxidative stress. Decreased level of gluthatione during flu is responsible for the severe pathology and complications. The purpose of our studies was to follow the effect of the combination S-adenosyl-L-methionine (SAM) as a precursor of glutathione and the specific neuraminidase inhibitor oseltamivir in influenza infected mice. SAM was given as a single daily dose of 50,100 and 150 mg/kg, starting from 5 days before infection until day 4th after viral inoculation. Oseltamivir was given in a daily dose of 2.5 mg/kg in two intakes for 5 days, starting from 4th hour before infection. End-point evaluation was 14 day survival rate, avarege survival time, index of protection, and virus titer in lungs.

The results showed that application of SAM alone did not have any antiviral prevention. In mice supplemented with oseltamivir only survival rate was 70%, but combination of oseltamivir and SAM in lower doses led to rising of 90% of protection. The present findings suggest that combined therapy of SAM as a precursor of glutathione and the specific inhibitor of inflienza virus replication oseltamivir could be effective on modulation of host defense mechanism(s) in low therapeutic doses.