Oxidative Stress as a Target for Medication of Influenza Virus Infection
Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences
“A perfection of means, and confusion of aims, seems to be our main problem.”
One of the life’s paradoxes is the fact that the molecule supporting aerobic life-oxygen-is not just essential for the energetic metabolism and for respiration, but almost equally involved in the ethiopatogenesis of numerous diseases and degenerative states due to oxygen-based reactive species called free radicals. Nature has selected and included, in an evolutionary manner, in the composition of living bodies, reactions generating free radicals with multiple roles: functional, intercellular communicational or destructive, cytolysis, etc. Free radicals occurs in the body, as the result of endogenous metabolic activity or of the local assimilation of some chemical pollutants at cellular level or at the level of several tissues, simultaneously or gradually. Due to their high reactivity, free radicals have been found responsible for many noxious effects on the living body. Oxidative stress is defined as an exaggerated production of oxygenated free radicals, accompanied by a dislocation of antioxidative agents. We cannot live without oxygen, since it is essential in the functioning of energy-producing cells. A body transforms and eliminates oxygen (as CO2) properly almost entirely (98%).
Free radicals produced by one’s own body play a role in the cell defense system, destroying bacteria and viruses, decomposing chemical pollutants, and neutralizing toxins.
The purpose of this work is to analyze the role of reactive oxygen species and development of oxidative stress in the pathogenesis of influenza viral infection, as an area of target for medication of flu. Attention should be focused on: (i) the effect of the virus on activation of phagocytic cells to release of free radical generation and pro-oxidant cytokines such as tumor necrosis factor; (ii) the effect of the virus on the pro-/antioxidant balance in host cells, including virally induced inhibition of antioxidant enzymes such as superoxide dismutase and virally induced increases in pro-oxidants such as nitric oxide; (iii) effects of the redox state of the cell on the genetic composition of the virus as well as ROS-mediated release of host cell nuclear transcription factor-kappa-B, resulting in increased viral replication; and (iiii) efficacy of antioxidants as therapeutic agents in viral diseases of both animal models and patients.
During influenza pandemics in last years many patients have died from severe complications associated with this pandemic despite receiving intensive care. This suggests that a definitive medical treatment for severe influenza-associated complications has not yet been established. Many studies have shown that superoxide anion produced by macrophages infiltrated into the virus-infected organs is implicated in the development of severe influenza- associated complications. Selected antioxidants, such as alpha-tocopherol, N-acetyl-L-cysteine, glutathione, ascorbic acid, 5, 7, 4-trihydroxy-8-methoxyflavone, catechins, quercetin 3-rhamnoside, isoquercetin etc. inhibit the proliferation of influenza virus and scavenge superoxide anion. The combination of antioxidants with antiviral drugs synergistically reduces the lethal effects of influenza virus infections. These results suggest that an agent with antiviral and antioxidant activities could be a drug of choice for the treatment of patients with severe influenza-associated complications. We hope this updates of knowledge for antioxidant therapy of flu could be use as a potential approach to overcome the influenza-associated complications.