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Melatonin as a principal component of red light therapy 375 light:dark rhythm or duration (Fig. 1A), the brain would be better equipped to guard against TCDD-in- duced oxidative and energy stress and cope with the altered glutathione redox balance. Increased GRx activity may be due to the increased production of its necessary cofactor NADPH resulting from stimu- lation of glucose-6-phosphate dehydrogenase by melatonin [34] (Fig. 1B). GPx and GRx serve as crit- ical enzymes in facilitating and restoring the antiox- idant properties of glutathione. Moreover, the trends that we have observed in the liver and brain suggest that red light treatment increases GSH while minimizing the accumulation of GSSG, hence the sig- nificant reductions in the GSSG/GSH ratios for both organs. Such a trend could be due to melatonin’s high affinity for free hydroxyl radicals [28], thereby preserving GSH while at the same time forestalling the conversion of GSH to GSSG (Fig. 1C). The LED-in- duced increase in cytochrome c oxidase activity (Fig. 1D) and ATP (Fig. 1E) in our studies and those of our collaborators could be mediated by melatonin as well, based upon the previous reports of melato- nin and mitochondrial health [19,27]. Various analyses [35–37] of the effects of light and LEDs on melatonin levels and rhythms in hu- mans have shown that while shorter wavelengths of blue (430 nm) and green (540 nm) light suppress salivary melatonin and shift the melatonin rhythm, red light (610 and 660 nm) has no effect on melato- nin suppression and slightly shortens the time be- fore dim light onset of melatonin secretion. While these studies do not directly confirm our proposal of melatonin as a mediator of red light therapy, they do highlight the unique relationship between red light wavelengths and melatonin. In future studies, we hope to address questions touching on the developmental and age-related nature of the mechanisms of action, as well as sea- sonal and diurnal factors. It is also possible that re- search into alternative therapies for neurological disturbances such as Parkinson’s disease, Alzhei- mer’s disease, and the sequellae of chronic diabe- tes might benefit from considering melatonin as an immediate and long-term tool. References [1] Reiter RJ, Pablos MI, Agapito TT, Guerrero JM. Melatonin in the context of the free radical theory of aging. Ann NY Acad Sci 1996;786:362–78. [2] Okatani Y, Wakatsuki A, Reiter RJ. Melatonin protects hepatic mitochondrial respiratory chain activity in senes- cence-accelerated mice. J Pineal Res 2002;32:143–8. [3] Poon AM, Liu ZM, Pang CS, Brown GM, Pang SF. Evidence for a direct action of melatonin on the immune system. Biol Signals 1994;3:107–17. [4] Bovic WT. The action of Schumann rays on living organisms. Bot Gaz 1916;61:1–29. [5] Downes A, Blunt TP. Researches on the effect of light upon bacteria and other organisms. Proc R Soc London 1877;26: 488–500. [6] Roelandts R. A new light on Niels Finsen, a century after his Nobel prize. Photodermatol Photoimmunol Photomed 2005;21:115–7. [7] Karu T. Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B 1999;49:1–17. [8] Karu TI. Low-power laser therapy. Biomedical photonics handbook. Boca Raton: CRC Press; 2003. ch. 48; p. 1–25. [9] Lane N. Cell biology: power games. Nature 2006;443:901–3. [10] Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buch- mann EV, Kane M, et al. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci USA 2003;100:3439–44. [11] Wong-Riley MT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, et al. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase. J Biol Chem 2005;280:4761–71. [12] Yeager RL, Lim J, Sanders RA, Oleske DA, Conklin J, Millsap DS, et al. Energy and glutathione redox balance in devel- oping brain after dioxin exposure and 670 nm light treat- ment [submitted for publication]. [13] Desmet KD, Paz DA, Corry JJ, Eells JT, Wong-Riley MT, Henry MM,et al.ClinicalandexperimentalapplicationsofNIR-LED photobiomodulation. Photomed Laser Surg 2006;24:121–8. [14] Whelan HT, Connelly JF, Hodgson BD, Barbeau L, Post AC, Bullard G, et al. NASA light-emitting diodes for the prevention of oral mucositis in pediatric bone marrow transplant patients. J Clin Laser Med Surg 2002;20:319–24. [15] Whelan HT, Smits Jr RL, Buchman EV, Whelan NT, Turner SG, Margolis DA, et al. Effect of NASA light-emitting diode irradiation on wound healing. J Clin Laser Med Surg 2001;19:305–14. [16] Liang HL, Whelan HT, Eells JT, Meng H, Buchmann E, Lerch- Gaggl A, et al. Photobiomodulation partially rescues visual cortical neurons from cyanide-induced apoptosis. Neuro- science 2006;139:639–49. [17] Weber GF. Final common pathways in neurodegenerative diseases: regulatory role of the glutathione cycle. Neurosci Biobehav Rev 1999;23:1079–86. [18] Yeager RL, Lim J, Millsap DS, Jasevicius AV, Sanders RA, Whelan HT, et al. 670 nm light treatment attenuates dioxin toxicity in the developing chick embryo. J Biochem Molec Toxicol 2006;20:271–8. [19] Martin M, Macias M, Escames G, Leon J, Acuna-Castroviejo D. Melatonin but not vitamins C and E maintains glutathione homeostasis in t-butyl hydroperoxide-induced mitochon- drial oxidative stress. FASEB J 2000;14:1677–9. [20] Takahashi JS, Murakami N, Nikaido SS, Pratt BL, Robertson LM. The avian pineal, a vertebrate model system of the circadian oscillator: cellular regulation of circadian rhythms by light, second messengers, and macromolecular synthesis. Recent Prog Horm Res 1989;45:279–348 [discus- sion-52]. [21] Natesan A, Geetha L, Zatz M. Rhythm and soul in the avian pineal. Cell Tissue Res 2002;309:35–45. [22] Akasaka K, Nasu T, Katayama T, Murakami N. Development of regulation of melatonin release in pineal cells in chick embryo. Brain Res 1995;692:283–6. [23] Herichova I, Zeman M, Mackova M, Griac P. Rhythms of the pineal n-acetyltransferase mrna and melatonin concentra- tions during embryonic and post-embryonic development in chicken. Neurosci Lett 2001;298:123–6.PDF Image | Melatonin as a principal component of red light therapy
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