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Involvement of nitric oxide in photobiomodulation

Prof. Harry Friedmann.
27. 8. 2002 (revised 10.2002)


Involvement of nitric oxide in photobiomodulation. The reason for the efficiency of BioNase in the treatment of rhinitis.

nitricOxide

To make things as simple as possible let me start by pointing out that it is by now accepted that irradiation of cells produce reactive oxygen species (ROS). [1]


The ROS (super oxide anion, singlet oxygen, hydrogen peroxide) probably all derive from the superoxide anion, which dismutates to yield singlet oxygen and hydrogen peroxide. [2,3]

Another ROS, the OH radical derives from the Fenton reaction of hydrogen peroxide with e.g. a ferrous ion. [3,4]
The super oxide anion is generated by the membrane-bound NADPH oxidase, which possesses a visible light absorbing flavocytochrome. [2,5]

Since the super oxide anion, singlet oxygen and OH are highly reactive and very short lived [6], the only ROS capable of penetrating the cell membrane and influencing the cell metabolism is hydrogen peroxide. This explains the similarity between biostimulation induced by introducing exogenous hydrogen peroxide at low concentrations [7] and photobiostimulation.

It also explains the similarity between photobiostimulation and the ligand-induced biostimulation via superoxide anion and hydrogen peroxide production. [5,8]

The light-absorbing flavocytochrome is the redox component of the NADPH oxidase.  Irradiation of this redox-type chromophore will accelerate the redox process by facilitating electron transfer to the oxygen molecule, thereby increasing superoxide anion and hence
hydrogen peroxide production at the cell membrane. Therefore, introduction into the medium of catalase, a large molecule which is unlikely to penetrate the cell membrane and which decomposes hydrogen peroxide, suppresses the effect of irradiation. [1,9]

Now, hydrogen peroxide reacts with the amino-acid Arginine to give nitric oxide in a nonenzymatic pathway. [10]

Therefore, irradiation of tissues with visible light yields enhanced nitric oxide production. [11]
Stimulation by nitric oxide (NO) is a systemic effect since NO combines with hemoglobin to form S-nitrosohemoglobin, which is transported by the blood stream and releases the nitric oxide where it is needed, relaxing vessels, regulating blood pressure and improving blood flow [12]

The photo-production of nitric oxide can be invoked to explain the systemic nature pf photobiostimulation [13].

The success of BIONASE in the non-invasive photo-biological treatment of allergic rhinitis [14], can now be understood by the antihistaminic action of nitric oxide. [15]

The effect of BIONASE can be enhanced by swallowing 4-5 pills of the food supplement L-Arginine with a glass of water, sweetened by a small amount of sugar, to ease digestion, every morning one hour before breakfast. Every pill contains 500mg of L-Arginine. This
should compensate for the increased amount of nitric oxide exhaled
by rhinitis patients.

[1] R. Lubart, M.Sinyakov, H. Friedmann, N. Grossman, L.Solodeeva, N,
Zurgiland and S. Belotsky, Photobiostimulation by visible light:
involvement of hydrogen peroxide.   Trends in Photochemistry and Photobiology 6, 169-174 (1999).

[2] A.W. Segal and A. Abo, The biochemical basis of the NADPH
oxidase of phagocytes. TIBS 18,43-47 (1993).

[3] B.R.Misra and H.P.Misra,Vasoactive intestinal peptide, a singlet
oxygen quencher. J.Biol.Chem.265 (26), 15371-4 (1990).

[4] C.Hadjur, G. Wagnieres, F. Ihringer, Ph. Monnier, H. van den Bergh,
Production of the free radicals superoxide anion and OH by irradiation of the photosensitizer  zinc(II) phtalocyanine J.Photochem. Photobiol. 38,196-202 (1997).

[5] B.Meier, A.R. Cross, J.T Hancock, F.J. Kaup and O.T.G. Jones,
Identification of a superoxide-generating NADPH oxidase system in human fibroblasts Biochem.J.275, 241-245 {1991).

[6] E.de Lamirande, Hong Jiang, A.Zini, H. Kodama and C. Gagnon,
Reactive oxygen species and sperm physiology. Reviews of reproduction 2,48-54 (1997).

[7] A.C.Murrell, M.J.O.Francis and L. Bromley, Modulation of fibroblast
proliferation by oxygen free radicals. Biochem J.265, 650-5 (1990).

[8] T, Karu, N.Smolyaninova and A. Zelenin, Long-term and short-term
responses of human lymphocytes to He-Ne laser radiation. Lasers life sci.4, 167-178 (1991).

[9] G.A. Callaghan, C.Riordan, W.S.Gilmore, I.A. McIntyre,
J.M.Allen and M. Hannigan, Reactive oxygen species inducible by low intensity laser irradiation alter DNA synthesis in the haemopoietic cell line U937, Lasers in surgery and medicine 19, 201-206 (1996).

[10] S.Nagase, K.Takemura, A.Ueda, A novel nonenzymatic pathway for
the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-Arginine.Biochem.Biophys.Res.Commun.233, 150-153 (1997).

[11] Q.Zhu, W.Yu, X.Yang, G.L.Hicks, R.J. Lanzaame and T.Wang, Photo-
irradiation improved preservation of the isolated rat heart. Lasers Surg. Med. 20, 332-9 (1997).

[12] J.S.Stamler. Li Jia, J.P.Eu, T.J.McMahon,I,T.Demchenko,
J.Bonaventura, K.Gernert, C.A.Piantadosi, Blood flow regulation by S-Nitrosohemoglobin in the physiological oxygen gradient, Science  276,2034-2037 (1997).

[13] S.Rochkind, M.Rousso, M.Nissan, M.Villarreal, L.Barr-Nea, L.Rees,
Systemic effects of low-power laser irradiation on the peripheral and central nervous system, cutaneous wounds and burns. Lasers Surg Med 9(2), 174-82 (1989).

[14] I. Neuman and Y. Finkelstein, Narrow-band red light photo-
therapy in perennial allergic rhinitis and nasal polyposis, Annals of allergy, asthma, & immunology 70,399-405 (1997).

[15] F.J. Van Overveld, H.Bult, P.A.Vermeire, A.G.Herman,
Nitroprusside, a nitric oxide generating drug, inhibits release of histamine and tryptase from human skin mast cells, Agents and actions, C38, 237-238 (1993).

Journal of Clinical Laser Medicine & Surgery, 2001, in press

Involvement of nitric oxide in photobiomodulation

Prof. Harry Friedmann.
27. 8. 2002 (revised 10.2002)


Involvement of nitric oxide in photobiomodulation. The reason for the efficiency of BioNase in the treatment of rhinitis.

nitricOxide

To make things as simple as possible let me start by pointing out that it is by now accepted that irradiation of cells produce reactive oxygen species (ROS). [1]


The ROS (super oxide anion, singlet oxygen, hydrogen peroxide) probably all derive from the superoxide anion, which dismutates to yield singlet oxygen and hydrogen peroxide. [2,3]

Another ROS, the OH radical derives from the Fenton reaction of hydrogen peroxide with e.g. a ferrous ion. [3,4]
The super oxide anion is generated by the membrane-bound NADPH oxidase, which possesses a visible light absorbing flavocytochrome. [2,5]

Since the super oxide anion, singlet oxygen and OH are highly reactive and very short lived [6], the only ROS capable of penetrating the cell membrane and influencing the cell metabolism is hydrogen peroxide. This explains the similarity between biostimulation induced by introducing exogenous hydrogen peroxide at low concentrations [7] and photobiostimulation.

It also explains the similarity between photobiostimulation and the ligand-induced biostimulation via superoxide anion and hydrogen peroxide production. [5,8]

The light-absorbing flavocytochrome is the redox component of the NADPH oxidase.  Irradiation of this redox-type chromophore will accelerate the redox process by facilitating electron transfer to the oxygen molecule, thereby increasing superoxide anion and hence
hydrogen peroxide production at the cell membrane. Therefore, introduction into the medium of catalase, a large molecule which is unlikely to penetrate the cell membrane and which decomposes hydrogen peroxide, suppresses the effect of irradiation. [1,9]

Now, hydrogen peroxide reacts with the amino-acid Arginine to give nitric oxide in a nonenzymatic pathway. [10]

Therefore, irradiation of tissues with visible light yields enhanced nitric oxide production. [11]
Stimulation by nitric oxide (NO) is a systemic effect since NO combines with hemoglobin to form S-nitrosohemoglobin, which is transported by the blood stream and releases the nitric oxide where it is needed, relaxing vessels, regulating blood pressure and improving blood flow [12]

The photo-production of nitric oxide can be invoked to explain the systemic nature pf photobiostimulation [13].

The success of BIONASE in the non-invasive photo-biological treatment of allergic rhinitis [14], can now be understood by the antihistaminic action of nitric oxide. [15]

The effect of BIONASE can be enhanced by swallowing 4-5 pills of the food supplement L-Arginine with a glass of water, sweetened by a small amount of sugar, to ease digestion, every morning one hour before breakfast. Every pill contains 500mg of L-Arginine. This
should compensate for the increased amount of nitric oxide exhaled
by rhinitis patients.

[1] R. Lubart, M.Sinyakov, H. Friedmann, N. Grossman, L.Solodeeva, N,
Zurgiland and S. Belotsky, Photobiostimulation by visible light:
involvement of hydrogen peroxide.   Trends in Photochemistry and Photobiology 6, 169-174 (1999).

[2] A.W. Segal and A. Abo, The biochemical basis of the NADPH
oxidase of phagocytes. TIBS 18,43-47 (1993).

[3] B.R.Misra and H.P.Misra,Vasoactive intestinal peptide, a singlet
oxygen quencher. J.Biol.Chem.265 (26), 15371-4 (1990).

[4] C.Hadjur, G. Wagnieres, F. Ihringer, Ph. Monnier, H. van den Bergh,
Production of the free radicals superoxide anion and OH by irradiation of the photosensitizer  zinc(II) phtalocyanine J.Photochem. Photobiol. 38,196-202 (1997).

[5] B.Meier, A.R. Cross, J.T Hancock, F.J. Kaup and O.T.G. Jones,
Identification of a superoxide-generating NADPH oxidase system in human fibroblasts Biochem.J.275, 241-245 {1991).

[6] E.de Lamirande, Hong Jiang, A.Zini, H. Kodama and C. Gagnon,
Reactive oxygen species and sperm physiology. Reviews of reproduction 2,48-54 (1997).

[7] A.C.Murrell, M.J.O.Francis and L. Bromley, Modulation of fibroblast
proliferation by oxygen free radicals. Biochem J.265, 650-5 (1990).

[8] T, Karu, N.Smolyaninova and A. Zelenin, Long-term and short-term
responses of human lymphocytes to He-Ne laser radiation. Lasers life sci.4, 167-178 (1991).

[9] G.A. Callaghan, C.Riordan, W.S.Gilmore, I.A. McIntyre,
J.M.Allen and M. Hannigan, Reactive oxygen species inducible by low intensity laser irradiation alter DNA synthesis in the haemopoietic cell line U937, Lasers in surgery and medicine 19, 201-206 (1996).

[10] S.Nagase, K.Takemura, A.Ueda, A novel nonenzymatic pathway for
the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-Arginine.Biochem.Biophys.Res.Commun.233, 150-153 (1997).

[11] Q.Zhu, W.Yu, X.Yang, G.L.Hicks, R.J. Lanzaame and T.Wang, Photo-
irradiation improved preservation of the isolated rat heart. Lasers Surg. Med. 20, 332-9 (1997).

[12] J.S.Stamler. Li Jia, J.P.Eu, T.J.McMahon,I,T.Demchenko,
J.Bonaventura, K.Gernert, C.A.Piantadosi, Blood flow regulation by S-Nitrosohemoglobin in the physiological oxygen gradient, Science  276,2034-2037 (1997).

[13] S.Rochkind, M.Rousso, M.Nissan, M.Villarreal, L.Barr-Nea, L.Rees,
Systemic effects of low-power laser irradiation on the peripheral and central nervous system, cutaneous wounds and burns. Lasers Surg Med 9(2), 174-82 (1989).

[14] I. Neuman and Y. Finkelstein, Narrow-band red light photo-
therapy in perennial allergic rhinitis and nasal polyposis, Annals of allergy, asthma, & immunology 70,399-405 (1997).

[15] F.J. Van Overveld, H.Bult, P.A.Vermeire, A.G.Herman,
Nitroprusside, a nitric oxide generating drug, inhibits release of histamine and tryptase from human skin mast cells, Agents and actions, C38, 237-238 (1993).

Journal of Clinical Laser Medicine & Surgery, 2001, in press