Abstract
With the appearance of the novel influenza A (H1N1) virus 2009 strain we have experienced a new influenza pandemic and 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 pyrrolidine dithiocabamate, N-acetyl-L-cysteine, glutathione, nordihydroguaiaretic acid, thujaplicin, resveratrol, (+)-vitisin A, ambroxol, ascorbic acid, 5,7,4-trihydroxy-8-methoxyflavone, catechins, quercetin 3-rhamnoside, iso- quercetin and oligonol, 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. This review article updates knowledge of antioxidant therapy as a potential approach to severe influenza-associated complications.
Highlights
With the appearance of the novel influenza A (H1N1) virus 2009 strain we have recently experienced a new influenza pandemic [1,2]
This superoxide anion induces injuries in non-infected cells. These superoxide anion-mediated pathways represent a part of the mechanisms of extensive tissue injury observed during severe influenza-associated complications [20], it has been suggested that an agent with antiviral and antioxidant activities could be a drug of choice for the treatment of patients with such severe complications [21,22]
Studies using J774.1 cells demonstrated that various other antioxidants, such as Trolox ®, deferoximine nesyiate, dithiothreitol, N-methyl-D-arginine, catalase and superoxide dismutase (SOD), did not inhibit the cytopathic effects of influenza virus infection [33,34]. These results suggest that the inhibition of influenza virus-induced apoptosis by PDTC is attributable to its antiviral activity rather than its antioxidant properties
Summary
With the appearance of the novel influenza A (H1N1) virus 2009 strain we have recently experienced a new influenza pandemic [1,2]. Intravenous drip infusion of peramivir has offered a new treatment option for children and infants suffering from influenza virus infections and patients where oral administration was difficult or not possible [13]. A young adult with pandemic influenza A (H1N1) virus infection was treated with intravenous peramivir, but died from severe viral pneumonia [16] These results suggest the need for development of new anti-influenza drugs utilizing alternative antiviral mechanisms and consideration of using anti-influenza drug combinations. Some such approaches have been explored, whereby a triple combination of amantadine, ribavirin and oseltamivir was highly active and synergistic against drug resistant influenza virus strains in vitro [17]
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