Transient responses of melatonin to stress
Melatonin and stress
Abstract
Melatonin and its metabolites are ubiquitous antioxidants that are produced in response to reactive oxygen species (ROS) in virtually all cells of the body. The highest reported melatonin values in plasma and sweat occur during heavy exercise both indoors and outdoors during the day. The advent of sweat biosensors with sufficient melatonin sensitivity provides pseudo real-time evidence that melatonin is produced throughout the body not just in the pineal gland. The role of the pineal gland appears to be to provide cyclic production of melatonin for the regulation of circadian rhythms as well as supplemental melatonin during periods of low cellular activity. Melatonin from the pineal gland represents only a small fraction of the body’s production capacity. Greater than 5 pg/ml min ramp rates for plasma and sweat melatonin have been reported during strenuous exercise in sunlight as compared to 0.15 pg/ml min ramp rates for plasma melatonin under dim light melatonin onset (DLMO) conditions. Sunlight and exercise, like fever, generates transient elevated levels of ROS in tissues with time constants measured in minutes or even seconds making this systemic antioxidant response potentially protective. Based on a simple accounting of ROS generated by sunlight, ROS we breathe, ROS we drink, and exercise, it appears that the body maintains a heightened basal level of ROS as part of its pathogen defense mechanisms. Current human lifestyles and modern enclosed spaces have substantially eliminated over 90% of the ROS which undermines one of the body’s primary defenses. With advanced age, the inability to maintain this protective barrier appears to make us more susceptible to disease.
References
2. Zhu M. (2018) Investigating eccrine sweat as a noninvasive biomarker resource. Ph.D.Thesis, Arizona State University. November 2018.
3. Brown GM, Young SN, Gauthier S et al. (1979) Melatonin in human cerebrospinal fluid in daytime; its origin and variation with age. Life Sci. 25 (11): 929-936.
4. Sack RL, Lewy AJ, Erb DL, et al. (1986) Human melatonin production decreases with age. J Pineal Res. 3 (4): 379-88.
5. Tan DX, Hardeland R (2021) The Reserve/Maximum Capacity of Melatonin's Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals. Molecules 26 (23): 7302. doi: 10.3390/molecules26237302.
6. Theron MM, Oosthuizen JM, Rautenbach MM (1984) Effect of physical exercise on plasma melatonin levels in normal volunteers. South African Med. J. 66: 838-841.
7. Smith JA, Padwick D, Mee TJ, et al. (1977) Synchronous nyctohemeral rhythms in human blood melatonin and in human post-mortem pineal enzyme. Clin. Endocrino.l (Oxf) 6 (3): 219-25.
8. Cassone VM, Warren WS, Brooks DS, et al. (1993) Melatonin, the pineal gland, and circadian rhythms. J. Biol. Rhythms 8 Suppl: S73-81.
9. Reiter RJ, Sharma R, Rosales-Coral S, et al. (2022) Melatonin: A mitochondrial resident with a diverse skill set. Life Sci. 301:120612. doi: 10.1016/j.lfs.2022.120612.
10. Venegas C, García JA, Escames G, et al. (2012) Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J. Pineal Res. 52 (2): 217-227.
11. Mittler R (2017) ROS are good. Trends Plant Sci. 22 (10): 11-19. doi: 10.1016/j.tplants.2016.08.002.
12. Tan DX, Manchester LC, Liu X, et al. (2013) Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin’s primary function and evolution in eukaryotes. J. Pineal Res. 54 (2): 127-138.
13. Reiter RJ, Ma C, Sharma R (2020) Melatonin in mitochondria: mitigating clear and present dangers. Physiology (Bestheda) 35 (2): 86-95.
14. Henrik S, István B, David M, et al. (2022) The innate immune system and fever under redox control: A narrative review. Curr. Med. Chem. 29 (25): 4324-4362. doi: 10.2174/0929867329666220203122239.
15. McCord JM, Wong K (1978) Phagocyte-produced free radicals: roles in cytotoxicity and inflammation. Ciba Found Symp. 8 (65):343-360.
16. Meyer T, Stockfleth E (2021) Light and skin. Curr. Probl. Dermatol. 55: 53-61.
17. Babu S, Manoharan S, Ottappilakkil H, et al. (2022) Role of oxidative stress-mediated cell death and signaling pathways in experimental fluorosis. Chem. Biol. Interact. 25: 365.
18. King MA, Clanton TL, Laitano O (2016) Hyperthermia, dehydration, and osmotic stress: unconventional sources of exercise-induced reactive oxygen species. Am. J. Physiol. Regul. Integr. Comp. Physiol. 310 (2): R105-114.
19. Hardeland R, Balzer I, Poeggeler B, et al. (1995) On the primary functions of melatonin in evolution: mediation of photoperiodic signals in a unicell, photooxidation, and scavenging of free radicals. J. Pineal Res. 18 (2): 104-111. doi: 10.1111/j.1600-079x.1995.tb00147.x.
20. Arnao MB, Hernández-Ruiz J (2021) Melatonin against environmental plant stressors: A review. Curr. Protein Pept. Sci. 22 (5): 413-429. doi: 10.2174/1389203721999210101235422.
21. Erben Y, Marquez CP, Prudencio M, et al. (2022) Race affects adverse outcomes of deep venous thrombosis, pulmonary embolism, and acute kidney injury in COVID-19 hospitalized patients. J. Vasc. Surg. Venous Lymphat. Disord 10: S2213-2333X(22)00356-0.
22. Baptiste DL, Turkson-Ocran RA, Ogungbe O, et al. (2022) Heterogeneity in cardiovascular disease risk factor prevalence among white, African American, African immigrant, and Afro-Caribbean adults: Insights from the 2010-2018 National Health Interview Survey. J. Am. Heart Assoc. 8: e025235.
23. Zhang R, Wang X, Ni L, et al. (2020) COVID-19: Melatonin as a potential adjuvant treatment. Life Sci.250: 117583. doi: 10.1016/j.lfs.2020.117583.
24. Cardinali DP (2020) High doses of melatonin as a potential therapeutic tool for the neurological sequels of covid-19 infection. Melatonin Res. 3: 311-317. doi:10.32794/11250064.
25. Pandi-Perumal SR, Cardinali DP, Reiter RJ, Brown GM (2020) Low melatonin as a contributor to SARS-CoV-2 disease. Melatonin Res. 3: 558-576. doi: 10.32794/mr11250079.
26. Castillo RR, Quizon GRA, Juco MJM, et al. (2020) Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series. Melatonin Res. 3: 297-310. doi: 10.32794/mr11250063.
27. Lan SH, Lee HZ, Chao CM, et al. (2022) Efficacy of melatonin in the treatment of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials. J. Med. Virol. 94 (5): 2102-2107. doi: 10.1002/jmv.27595.
28. Tan DX, Reiter RJ (2022) Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality. Life Sci. 294: 120368. doi: 10.1016/j.lfs.2022.120368.
29. Zastrow L, et al. (2015) Free radical threshold value: a new universal body constant. Skin Pharmacol. Physiol. 28 (5): 264-268. doi: 10.1159/000435893.
30. Meinke MC, et al. (2021) Wavelength, dose, skin type, and skin model related to radical formation in skin. Biophysical. Rev. 13: 1091-1100.
31. Troiani ME, Reiter RJ, Vaughan MK, et al. (1988) Swimming depresses nighttime melatonin content without changing N-acetyltransferase activity in the rat pineal gland. Neuroendocrinology 47 (1): 55-60. doi: 10.1159/000124891.
32. Kim JH, Elkhadem AR, Duffy JF. (2022) Circadian rhythm sleep-wake disorders in older adults. Sleep Med. Clin. 17 (2): 241-252. doi: 10.1016/j.jsmc.2022.02.003.
33. Hwang Y, McPhillips MV, Talwar S, et al. (2022) The relationship between light exposure before bedtime and daytime sleepiness among people living with cognitive impairment. J. Appl. Gerontol. 41 (7): 1686-1694.
34. Brown TM, Brainard GC, Cajochen C, et al. (2022) Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults. PLoS Biol. 20 (3): e3001571.
This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Melatonin Res., copyright is retained by the authors. Articles are licensed under an open access Creative Commons CC BY 4.0 license, meaning that anyone may download and read the paper for free. In addition, the article may be reused and quoted provided that the original published version is cited. These conditions allow for maximum use and exposure of the work, while ensuring that the authors receive proper credit.
In exceptional circumstances articles may be licensed differently. If you have specific condition (such as one linked to funding) that does not allow this license, please mention this to the editorial office of the journal at submission. Exceptions will be granted at the discretion of the publisher.
