Melatonin: An integrative approach to regulate immune homeostasis against oxidative stress

  • Shraddha Rastogi Pineal Research Laboratory, Department of Zoology, Institute of Science Banaras Hindu University, Varanasi-221005, India
  • Chandana Haldar Pineal Research Laboratory, Department of Zoology, Institute of Science Banaras Hindu University, Varanasi-221005, India

Abstract

Several factors such as environment, pathogens, lifestyle, stress, radiation etc. are involved in increasing oxidative overload by affecting the antioxidant status or free oxygen radical generation. The elevated concentrations of reactive oxygen and nitrogen species (ROS/RNS) causes redox imbalance that exacerbates free radicals generation causing oxidative stress which impairs the antioxidant defense pathways resulting into molecular damage to vital structures and functions thereby causing cell death. Oxidative stress increases susceptibility to illness and disease because as a part of intrinsic defense mechanism, brain send signals to the endocrine system. Oxidative stress is also implicated in various life-threatening diseases wherein, free radicals far outnumber the naturally occurring antioxidants.  To maintain the redox balance, a continual supply of antioxidants is necessary in order to obtain the maximum benefits. In recent years, the pharmaceutical market has been flooded with various antioxidant supplements that claim to reduce oxidative overload and increase longevity, however they have a few drawbacks such as auto-oxidation and impermeability inside the cell. Hence, a strong integrative approach is required to counteract oxidative stress without affecting normal physiology. Melatonin, a lipophilic molecule synthesized by the pineal gland is a potent intrinsic non-enzymatic antioxidant as well as an immunomodulator. Melatonin is a part of intrinsic system that has the ability to regulate antioxidative, immunologic and other physiological processes simultaneously. Therefore, in this review we have highlighted properties of melatonin and introduced it as a strong candidate against redox imbalance induced clinical pathologies thereby increasing longevity and survival.

References

Ahmad R, Gupta S, Haldar C (2012) Age dependent expression of melatonin membrane receptor (MT1, MT2) and its role in regulation of nitrosative stress in tropical rodent Funambulus pennanti. Free Radic Res, 46(2), 194-203

Amer, J., H. Ghoti, et al. (2006) Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br J Haematol 132(1): 108-113

Bahorun, MA Soobrattee, V Luximon-Ramma, OI Aruoma (2006) Free Radicals and Antioxidants in Cardiovascular Health and Disease. Internet Journal of Medical Update, Vol. 1, No. 2, Jul-Dec

Belikov, A. V., B. Schraven, et al. (2015) T cells and reactive oxygen species. J Biomed Sci 22: 85

Berlett, B. S. and E. R. Stadtman (1997) Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272(33): 20313-20316

Betteridge, D. J. (2000) What is oxidative stress? Metabolism 49(2 Suppl 1): 3-8

Bhabak, K. P. and G. Mugesh (2010) Functional mimics of glutathione peroxidase: bioinspired synthetic antioxidants. Acc Chem Res 43(11): 1408-1419

Butterfield, D. A. (2002) Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res 36(12): 1307-1313

Calabrese V, Cornelius C, Trovato A, Cavallaro M, Mancuso C, Di Rienzo L; et al. (2010) The hormetic role of dietary antioxidants in free radical-related diseases. Current Pharmaceutical Design. 16 (7): 877–83

Cappellini, M. D. and G. Fiorelli (2008) Glucose-6-phosphate dehydrogenase deficiency. Lancet 371(9606): 64-74

Carrillo-Vico, A., R. J. Reiter, (2006) The modulatory role of melatonin on immune responsiveness. Curr Opin Investig Drugs, 7(5), 423-431

Carrillo-Vico, A., P. J. Lardone, (2013) Melatonin: buffering the immune system. Int J Mol Sci, 14(4), 8638-8683

Chandrashekara, S. (2012) The treatment strategies of autoimmune disease may need a different approach from conventional protocol: a review. Indian J Pharmacol 44(6): 665-671

Chelikani, P., I. Fita, et al. (2004) Diversity of structures and properties among catalases. Cell Mol Life Sci 61(2): 192-208

Christen, Y. (2000) Oxidative stress and Alzheimer disease. Am J Clin Nutr 71(2): 621S-629S

Cooper, G. S., J. Wither, et al. (2010) Occupational and environmental exposures and risk of systemic lupus erythematosus: silica, sunlight, solvents. Rheumatology (Oxford) 49(11): 2172-2180

Currier, N. L., L. Z. Sun, (2000) Exogenous melatonin: quantitative enhancement in vivo of cells mediating non-specific immunity J Neuroimmunol, 104(2), 101-108

Davies KJ (2000) Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life, 50(4-5), 279-89

Deponte, M. (2013) Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 1830(5): 3217-3266

Dizdaroglu M, Jaruga P (2012) Mechanisms of free radical-induced damage to DNA. Free Radical Research; 46(4) 382-419

Droge, W. (2002) Free radicals in the physiological control of cell function. Physiol Rev 82(1): 47-95

Evans, M. D. and M. S. Cooke (2004) Factors contributing to the outcome of oxidative damage to nucleic acids. Bioessays 26(5): 533-542

Hayyan M, Hashim MA, Al Nashef IM (2016) Superoxide Ion: Generation and Chemical Implications. Chemical Reviews. 116 (5): 3029–85

Jou, M. J., T. I. Peng, (2007) Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis. J Pineal Res, 43(4), 389-403

Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ (2005) Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic Biol Med. 1;39(5):584-589

Klein, D. C., S. L. Coon, (1997) The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland. Recent Prog Horm Res, 52, 307-357, discussion 357-308

Kumagai, S., T. Jikimoto, et al. (2003) Pathological roles of oxidative stress in autoimmune diseases Rinsho Byori 51(2): 126-132

MacNee, W. (2001) Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 429(1-3): 195-207

Li, X., P. Fang, et al. (2013) Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol 6:19

Manchester, L. C., A. Coto-Montes, (2015) Melatonin: an ancient molecule that makes oxygen metabolically tolerable J Pineal Res, 59(4):403-419

Mahajan A. and V. R. Tandon, (2004) Antioxidants and rheumatoid arthritis. Journal of Indian Rheumatology Association, vol. 12, pp. 139–142

Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signalling for suicide and survival. Journal of Cellular Physiology. 192 (1): 1–15

Marnett LJ. (1999) Lipid peroxidation-DNA damage by malondialdehyde. Mutation research; 424(1-2):83–95

Mironczuk-Chodakowska, I., A. M. Witkowska, et al. (2018) Endogenous non-enzymatic antioxidants in the human body. Adv Med Sci 63(1): 68-78

Ogata, T., T. Senoo, et al. (2016) Mitochondrial superoxide dismutase deficiency accelerates chronological aging in the fission yeast Schizosaccharomyces pombe. Cell Biol Int 40(1):100-106

Pacher, P., J. S. Beckman, et al. (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87(1):315-424
Pisoschi, A. M. and A. Pop (2015) The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 97:55-74

Pizzino, G., N. Irrera, et al. (2017) Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev 2017:8416763

Poeggeler B. R., J. Reiter (1996) Melatonin and structurally-related, endogenous indoles act as potent electron donors and radical scavengers in vitro. Redox Rep, 2(3):179-184

Poeggeler, B., S. Saarela (1994) Melatonin--a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci, 738, 419-420

Pogozelski, W.K.; T.D. Tullius (1998) Oxidative strand scission of nucleic acid: routes initiated by hydrogen abstraction from the sugar moiety. Chem. Rev. 98 (3): 1089–1107

Ramalingam, M. and S. J. Kim (2012) Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases. J Neural Transm (Vienna) 119(8): 891-910

Rattan, S. I. (2006) Theories of biological aging: genes, proteins, and free radicals. Free Radic Res 40(12): 1230-1238

Reiter, R. J., J. C. Mayo, (2016) Melatonin as an antioxidant: under promises but over delivers. J Pineal Res 61(3), 253-278

Rodriguez, C., J. C. Mayo (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res, 36(1), 1-9, 2004

Saremi, A. and R. Arora (2010) Vitamin E and cardiovascular disease. Am J Ther 17(3): e56-65

Singh, M. and H. R. Jadhav (2014) Melatonin: functions and ligands. Drug Discov Today, 19(9), 1410-1418

Slominski, A., T. W. Fischer. (2005) On the role of melatonin in skin physiology and pathology. Endocrine 27(2), 137-148

Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR (2000) Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept, 9(3-4), 137-59

Tan, D. X., L. C. Manchester (2000) Melatonin directly scavenges hydrogen peroxide: a potentially new metabolic pathway of melatonin biotransformation. Free Radic Biol Med, 29(11), 1177-1185

Tan, D. X., L. C. Manchester (1999) Identification of highly elevated levels of melatonin in bone marrow: its origin and significance. Biochem Biophys Acta, 1472(1-2), 206-214

Vigor, C., J. Bertrand-Michel, et al. (2014). Non-enzymatic lipid oxidation products in biological systems: assessment of the metabolites from polyunsaturated fatty acids. J Chromatogr B Analyt Technol Biomed Life Sci 964: 65-78

Vriend, J. and R. J. Reiter (2015) The Keap1-Nrf2-antioxidant response element pathway: a review of its regulation by melatonin and the proteasome Mol Cell Endocrinol, 401, 213-220

Walston J., Q. Xue, R. D. Semba, (2006) Serum antioxidants, inflammation, and total mortality in older women. American Journal of Epidemiology, vol. 163, pp. 18–26

Wilson, A. and A. Trumpp (2006) Bone-marrow hematopoietic-stem-cell niches. Nat Rev Immunol, 6(2), 93-106
Published
2018-06-30
How to Cite
[1]
Rastogi, S. and Haldar, C. 2018. Melatonin: An integrative approach to regulate immune homeostasis against oxidative stress. Journal of Biological Sciences and Medicine. 4, 2 (Jun. 2018).
Section
Review Articles