Anti-Viral Effects of Nitric Oxide (NO)
Alpha Keto Acids Including Pyruvate Increase Nitiric Oxide (NO) Levels Needed to Kill Viral Infections
 HSV-1 infected cells treated with N115.
In four separate trials it was demonstrated that inhaled sodium pyruvate regulated the synthesis of NO and also protected it from destruction by excess hydrogen Peroxide. The underlying chronic inflammatory process in lung infections, which induces NO synthesis, needed to kill infecting organisms also produces excess oxygen radicals, which will destroy NO. Infected and non-infected lungs and other irritants have been shown to enhance NO production by alveolar macrophages in rats, which also produces an increased level of oxygen radical that can react directly with NO to produce NO2 and peroxynitrites. Peroxynitrite ion and peroxynitrous acid, formed from the interaction of NO and superoxide anions, specifically hydrogen peroxide, are strong oxidant species that work against NO by inducing single-strand breaks in DNA, increasing the levels of inflammatory mediators by activating NF Kappa B and enhancing replication of infective agents, including viruses. This has been demonstrated in Karposi’s sarcoma in AIDS patients. Hydrogen peroxide and peroxynitrites are very toxic and disruptive to cell membranes via lipid peroxidation not only leading to cell death, but also dysfunction of many cellular membrane functions, such as transport mechanisms. Their effect can destroy the ability of white blood cells to kill invading microorganisms. Over expression of hydrogen peroxide and peroxynitrite has been show to destroy immune cells at sites of infection, including CD4 and CD8 cells. Over expression of peroxynitrite has been shown to enhance bacterial and viral replication at infected sites do to peroxynitrites ability to enhance NF kappa B expression. Peroxynitrites, cause injury through the production of chemokines and contribute to viral pathogenesis and they enhance viral mutations. Excess hydrogen peroxide and peroxynitrites can also react with antimicrobial and antiviral drugs to destroy their ability to kill infections. Damaged or infected lungs produce even higher levels of peroxynitrite, which damages non damaged cells and immune cells and drugs needed to treat the damage. Infections with herpes simplex virus I (HSV-1) induces a persistent nuclear translocation of NF kappa B, which is dramatically enhanced by hydrogen peroxide and peroxynitrite. The activation of NF kappa B promotes efficient replication by HSV. In epithelial cells HSV-1 induces NF kappa B causing persistent activation of NF Kappa B, which is a critical regulator of HSV-1 replication. In AIDs patients, HIV-1 also triggers and activates NF kappa B and AIDS patients have elevated levels of hydrogen peroxide and peroxynitrite, which contributes to the etiology of AIDS related dementia, persistent immunosuppression and Kaposi’s sarcoma. Hydrogen peroxide and peroxynitrite have also been shown to be very destructive to CD4 and CD8 cells. We have discovered that alpha keto acids including sodium pyruvate, can decrease the levels and production of hydrogen peroxide and while protecting and increasing the levels NO needed to enhance viral destruction in HSV-1 infected cells. In combination with an antiviral drug, pyruvate completed eliminated the virus form the infected cells.
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