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Nitric Oxide is Now Known as a Fundamental Molecule in the Fields of Neuroscience, Physiology, and Immunology

 

Nitric oxide or nitrogen monoxide is a compound with the chemical formula NO. Nitric oxide should not be confused with nitrous oxide (N2O), a general anesthetic or with nitrogen dioxide (NO2) a greenhouse gas. Despite being a simple molecule, nitric oxide is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry. It is also an air pollutant produced by cigarette smoke, automobile engines and power plants.

Nitric oxide is an important messenger molecule produced naturally in the body and is involved in many physiological and pathological processes and was proclaimed “Molecule of the Year” in 1992. The Nobel Prize in Medicine was awarded in 1998 for the discovery of "nitric oxide acting as a signaling molecule in the cardiovascular system". Nitric oxide is now known as a fundamental molecule in the fields of neuroscience, physiology, and immunology. Nitric oxide also plays a major role in the human body’s defense against infections.
 

NO is the most innovative treatment ever discovered in our fight against pathogens


Nitric oxide could very well be the most innovative treatment ever discovered in our fight against pathogens since the discovery of penicillan. Retrospectively, this may not turn out to be such a big surprise, since it is a naturally generated molecule within the body’s innate immune system in response to any invading pathogen. Not only does nitric oxide act as an indiscriminate broad spectrum killer molecule but also its’ antimicrobial action is localized, short acting and well tolerated by the body’s own cells. These characteristics consequently ameliorate concomitant systemic side effects, nitric oxide tolerance and negative inflammatory response. All these activities combined, could “buy time” until the body’s acquired immune system takes over to protect the body from similar pathogens.

Nitric oxide is a naturally generated molecule. It is a part of the innate immune response produced by phagocytic cells present in exposed organs such as nasopharynx, lungs and wounds as non-specific broad-range, chemically reactive,anti-microbial, cytotoxic agent. It has been shown that Influenza A (seasonal flu) and Rhino (common cold) viruses are highly susceptible to nitric oxide.  The mechanism of cytotoxic action in bacteria has been identified (viral targets currently being investigated), and it has been shown that unlike antibiotics, microbes are unlikely to develop a resistance to nitric oxide. More importantly, studies have demonstrated that the concentration of nitric oxide in Nitrisol, that is cytotoxic to microbes, does not harm mammalian cells and is safe for use.

In summary, there are six novel reasons why nitric oxide suspended in saline (Nitrisol™) should be aggressively explored as a novel front line prevention for infections: 1) Nitric oxide kills/inactivates bacteria, viruses, fungi and parasites; with limited resistance development  2) Nitric oxide has a biological life of only a few seconds, and thus does not accumulate in the body; 3) Nitric oxide possesses anti-inflammatory activity; 4) Nitric oxide is well tolerated by host cells; 5) Nitric oxide enhances the acquired immune response and 6) Nitric oxide can be directly delivered easily to the infected organ. Further, should nitric oxide demonstrate itself to be effective as a therapeutic agent, it is already an approved drug for use as a vasodilator in the full term human infant.

 

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References

 

1. Miller C, Rawat M, Johnson T, Av-Gay Y. Innate protection of mycobacteria against the antimicrobial activity of nitric oxide is provided by mycothiol. Antimicrobial Agents And Chemotherapy 2007;51(9):3364-3366.

2. McMullin B, Chittock D, Roscoe D, Garcha H, Wang L, Miller C. The antimicrobial effect of nitric oxide on the bacteria that cause nosocomial pneumonia in mechanically ventilated patients in the icu. Resp Care 2005;50(11):1451-1456.

3. Ghaffari A, Jalili RB, Li Y, Ghaffari M, Miller C.C, Ghahary A. Antimicrobial Safety and Efficacy of Gaseous Nitric Oxide on Bacterial and Human Skin Cells. Wound Rep Reg 2007;15(3):368-377.

4. Miller C, McMullin B, Ghaffari A, Miller J, Stenzler A, Pick N, Roscoe D, Ghahary A, Road J, Av Gay Y. Gaseous nitric oxide bactericidal activity retained during intermittent high-dose short duration exposure Nitric Oxide 2009;20 :16-23.

5. Fang FC. Mechanisms of nitric oxide-related antimicrobial activity. J Clin Invest 1997;99:2818-2825.

6. Ghaffari A, Neil D.H, Ardakani A, Road J, Ghahary A, Miller CC. A direct nitric oxide gas delivery system for bacterial and mammalian cell cultures. Nitric Oxide 2005:12(3);129-140.

7. DeGroote M.A., Fang F.C. (1999) Antimicrobial properties of nitric oxide. In Fang FC (ed). Nitric oxide and infection. Kluwer Academic/Plenum Publishers, New York

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