Regulation of Nitric Oxide (NO)
Effect of Inhaled Sodium Pyruvate on Regulating Nitric Oxide (NO) in Inflammatory Lung Disease
Nitric oxide (NO) produces clinically useful bronchodilation (1) and is also used by the body to kill bacteria, fungal infections, viral infections, and tumors. The pharmaceutical industry is
answering the challenge of the link between inflammation and lung diseases by developing and launching a number of antiinflammatory compounds designed to reduce and manage lung
inflammation, or to “up regulate” components of the inflammatory process like NO to fight lung infections and tumors. The currently FDA recognized primary markers for lung disease
include oxygen radicals (hydrogen peroxide), NO, histamines, leukotrienes, prostaglandins, pro-inflammatory cytokines, interleukins and chemokines. The two major antiinflammatory
agents used to treat lung inflammation are the corticosteriods and anti-leukotrienes. The corticosteriods reduce lung inflammation by preventing the activation and migration of inflammatory cells into the lungs. The ability of inhaled steroids to reduce lung inflammation can be measured by the decreased levels of the above mentioned inflammatory markers. The problem is that not all patients’ respond, and corticosteriods can have serious toxic side effects. The anti-leukotrienes work by inhibiting the synthesis of leukotrienes and include the products Singulair,
Accolate, and Zyflo. Again their efficacy is limited to about 50% of patients treated, and they do not significantly improve FEV1* values. The ability to up regulate the synthesis of NO is also
being developed by many companies that are developing the use of arginine or arginine analogs to fight lung infections and cancers. The problem with inhaled arginine or arginine analogs
has been their toxicity.
Thus, the ability of inhaled pyruvate to “up regulate” or down regulate NO levels in lungs and to protect NO from other oxygen radicals, allows NO to deactivate NF-kappa B, which, in turn,
will reduce lung NO levels and reduce lung inflammation. In human clinical studies, sodium pyruvate at lower concentrations decreased hydrogen peroxide and NO levels in patients treated
by inhalation therapy. Sodium pyruvate inhalation at higher concentrations increased NO levels in expired breaths, of asthmatics and moderate and severe COPD patients, that could be
used to treat lung cancers, lung infections, especially in patients with cystic fibrosis. Patients with cystic fibrosis, produce very low levels of NO, that allows viral replication to occur. In HSV-1
infected cells, sodium pyruvate at the higher concentrations, reduced viral loads and in combination with antiviral agents, eliminated the virus completely from the infected cells.
*Forced esxpiratory volume.
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