Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism
Open accessAbstract
Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Melatonin occurs in mitochondria in higher abundance compared to blood, due to higher requirements for an antioxidant pool in mitochondria containing electron transport chain.
“Melatonin occurs in mitochondria in higher abundance compared to blood. This is due to the higher requirements for an antioxidant pool in mitochondria containing electron transport chain (Tan et al. 2015).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Tan et al. 2015
Melatonin is involved with mitochondrial homeostasis, genomic regulation, modulation of inflammatory and immune cytokines, and systemic and acute anti-inflammatory properties.
“Finally, melatonin is involved with multiple activities that include mitochondrial homeostasis, genomic regulation, modulation of inflammatory and immune cytokines, directly impacting both systemic and acute anti-inflammatory properties as well as indications around its potential role in phase separation [25,26].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [25]
Microbial influences on the serotonergic and melatonergic systems have been identified.
“An investigation into gut microbiota has identified microbial influences on the serotonergic and melatonergic systems [25].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [25]
Levels of melatonin are higher in mitochondria compared with blood levels, most likely due to the greater antioxidant requirements with the copious amounts of free radicals generated through the electron transport chain.
“Levels of melatonin are known to be higher in mitochondria compared with blood levels, most likely due to the greater antioxidant requirements with the copious amounts of free radicals generated through the electron transport chain [25].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [25]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · see citing works
ISOLATION OF MELATONIN, THE PINEAL GLAND FACTOR THAT LIGHTENS MELANOCYTES 1
Lerner, A. B., Case, J. D., TAKAHASHI, Y., Lee, T. H., & Mori, W. (1958) · Journal of the American Chemical Society · doi:10.1021/ja01543a060 · Cited by 1,759 · see citing works
Tan, D., Manchester, L. C., Terron, M. P., Flores, L. J., & Reiter, R. J. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00407.x · Cited by 1,601 · see citing works
Self-citationDubbels, R., Reiter, R. J., Klenke, E., Goebel, A., Schnakenberg, E., Ehlers, C., SCHIWARA, H. W., & Schloot, W. (1995) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1995.tb00136.x · Cited by 1,104 · see citing works
Self-citationExtrapineal melatonin: sources, regulation, and potential functions
Acuña-Castroviejo, D., Escames, G., Venegas, C., Díaz-Casado, M. E., Lima‐Cabello, E., López, L. C., Rosales‐Corral, S., Tan, D., & Reiter, R. J. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1579-2 · Cited by 1,086 · see citing works
Self-citationThe melatonin rhythm: both a clock and a calendar
Reiter, R. J. (1993) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923947 · Cited by 997 · see citing works
Self-citationOn the free radical scavenging activities of melatonin's metabolites, AFMK and AMK
Galano, A., Tan, D. X., & Reiter, R. J. (2012) · Journal of Pineal Research · doi:10.1111/jpi.12010 · Cited by 829 · see citing works
Self-citationHattori, A., Migitaka, H., Iigo, M., Itoh, M., Yamamoto, K., Ohtani‐Kaneko, R., Hara, M., Suzuki, T., & Reiter, R. J. (1995) · PubMed · Cited by 827 · see citing works
Self-citationAkhavan, O., Ghaderi, E., & Esfandiar, A. (2011) · The Journal of Physical Chemistry B · doi:10.1021/jp200686k · Cited by 670 · see citing works
Melatonin: The chemical expression of darkness
Reiter, R. J. (1991) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(91)90087-9 · Cited by 634 · see citing works
Self-citationMauriz, J. L., Collado, P. S., Veneroso, C. E., Reiter, R. J., & González‐Gallego, J. (2012) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2012.01014.x · Cited by 627 · see citing works
Self-citationFunctional roles of melatonin in plants, and perspectives in nutritional and agricultural science
Tan, D. X., Hardeland, R., Manchester, L. C., Korkmaz, A., Ma, S., Rosales‐Corral, S., & Reiter, R. J. (2011) · Journal of Experimental Botany · doi:10.1093/jxb/err256 · Cited by 627 · see citing works
Self-citationTan, D. X., Manchester, L. C., Liu, X., Rosales‐Corral, S., Acuña-Castroviejo, D., & Reiter, R. J. (2012) · Journal of Pineal Research · doi:10.1111/jpi.12026 · Cited by 584 · see citing works
Self-citationExtrapineal melatonin: analysis of its subcellular distribution and daily fluctuations
Venegas, C., García, J. A. G., Escames, G., Ortiz, F., López, A., Doerrier, C., García‐Corzo, L., López, L. C., Reiter, R. J., & Acuña-Castroviejo, D. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00931.x · Cited by 580 · see citing works
Self-citationSignificance of Melatonin in Antioxidative Defense System: Reactions and Products
Tan, D., Manchester, L. C., Reiter, R. J., Qi, W., Karbownik‐Lewińska, M., & Calvo, J. R. (2000) · Neurosignals · doi:10.1159/000014635 · Cited by 566 · see citing works
Self-citationHardeland, R., Tan, D., & Reiter, R. J. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00701.x · Cited by 474 · see citing works
Self-citationMammalian melatonin receptors: molecular biology and signal transduction
von Gall, C., Stehle, J. H., & Weaver, D. R. (2002) · Cell and Tissue Research · doi:10.1007/s00441-002-0581-4 · Cited by 455 · see citing works
Human Melatonin Production Decreases With Age
Sack, R. L., Lewy, A. J., Erb, D. L., Vollmer, W. M., & Singer, C. M. (1986) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1986.tb00760.x · Cited by 415 · see citing works
Hardeland, R., & Pöeggeler, B. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00040.x · Cited by 400 · see citing works
Melatonin: Both master clock output and internal time-giver in the circadian clocks network
Pévet, P., & Challet, É. (2011) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2011.07.001 · Cited by 372 · see citing works
Tan, D. X., Hardeland, R., Manchester, L. C., Paredes, S. D., Korkmaz, A., Sainz, R. M., Mayo, J. C., Fuentes‐Broto, L., & Reiter, R. J. (2009) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2009.00118.x · Cited by 365 · see citing works
Self-citationMurch, S. J., KrishnaRaj, S., & Saxena, P. K. (2000) · Plant Cell Reports · doi:10.1007/s002990000206 · Cited by 364 · see citing works
Stevens, R. G., Blask, D. E., Brainard, G. C., Hansen, J., Lockley, S. W., Provencio, I., Rea, M. S., & Reinlib, L. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.10200 · Cited by 357 · see citing works
Genetic Control of Melatonin Synthesis in the Pineal Gland of the Mouse
Ebihara, S., Marks, T. N., Hudson, D. J., & Menaker, M. (1986) · Science · doi:10.1126/science.3941912 · Cited by 354 · see citing works
Phytomelatonin: Assisting Plants to Survive and Thrive
Reiter, R. J., Tan, D., Zhou, Z., Cruz, M., Fuentes‐Broto, L., & Galano, A. (2015) · Molecules · doi:10.3390/molecules20047396 · Cited by 335 · see citing works
Self-citationMayo, J. C., Sainz, R. M., Tan, D., Hardeland, R., León, J., Rodrı́guez, C., & Reiter, R. J. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.05.002 · Cited by 332 · see citing works
Self-citationMelatonin in the skin: synthesis, metabolism and functions
Slominski, A. T., Tobin, D. J., Zmijewski, M. A., Wortsman, J., & Paus, R. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2007.10.007 · Cited by 331 · see citing works
Lowes, D. A., Webster, N. R., Murphy, M. P., & Galley, H. F. (2013) · British Journal of Anaesthesia · doi:10.1093/bja/aes577 · Cited by 314 · see citing works
Huether, G. (1993) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923948 · Cited by 306 · see citing works
Liu, R.-Y., Zhou, J.-N., van Heerikhuize, J., Hofman, M. A., & Swaab, D. F. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.1.5394 · Cited by 304 · see citing works
Clinical Uses of Melatonin: Evaluation of Human Trials
Sanchez-Barcelo, E. J., Mediavilla, M. D., Tan, D. X., & Reiter, R. J. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710791233689 · Cited by 301 · cited 1× · see citing works
“This cascade of reaction with ROS and NOS contributes to its superior protective effects in animal and human studies against oxidative stress [103,104]; this also expands melatonin’s use in industrial fields.”
BackgroundSelf-citationRoseboom, P. H., Namboodiri, M. A. A., Zimonjic, D. B., Popescu, N. C., Rodríguez, I. R., Gastel, J. A., & Klein, D. C. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00273-3 · Cited by 295 · see citing works
Hardeland, R. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12090 · Cited by 285 · see citing works
Afreen, F., Zobayed, S. M. A., & Kozai, T. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00337.x · Cited by 283 · see citing works
Melatonin as a powerful bio-antioxidant for reduction of graphene oxide
Esfandiar, A., Akhavan, O., & zad, A. I. (2011) · Journal of Materials Chemistry · doi:10.1039/c1jm10151j · Cited by 275 · see citing works
Zhou, J., Liu, R., Kamphorst, W., Hofman, M. A., & Swaab, D. F. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00065.x · Cited by 269 · see citing works
Melatonin feedback on clock genes: a theory involving the proteasome
Vriend, J. P., & Reiter, R. J. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12189 · Cited by 268 · see citing works
Self-citationCalorie restriction in rhesus monkeys
Mattison, J. A. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00146-8 · Cited by 255 · see citing works
Tan, D. X., Manchester, L. C., Burkhardt, S., Sainz, R. M., Mayo, J. C., Kohen, R., Shohami, E., Huo, Y., Hardeland, R., & Reiter, R. J. (2001) · The FASEB Journal · doi:10.1096/fj.01-0309fje · Cited by 253 · see citing works
Self-citationPineal Melatonin Rhythm: Reduction in Aging Syrian Hamsters
Reiter, R. J., Richardson, B. A., Johnson, L. Y., Ferguson, B. N., & Dinh, D. T. (1980) · Science · doi:10.1126/science.7434032 · Cited by 251 · see citing works
Self-citationRessmeyer, A., Mayo, J. C., Zelosko, V., Sainz, R. M., Tan, D., Pöeggeler, B., Antolı́n, I., Zsizsik, B. K., Reiter, R. J., & Hardeland, R. (2003) · Redox Report · doi:10.1179/135100003225002709 · Cited by 238 · see citing works
Self-citationTan, D. X., Manchester, L. C., Mascio, P. D., Martinez, G. R., Prado, F. M., & Reiter, R. J. (2007) · The FASEB Journal · doi:10.1096/fj.06-7745com · Cited by 232 · see citing works
Self-citationThe Effects of Oral Melatonin on Skin Color and on the Release of Pituitary Hormones
Nordlund, J. J., & Lerner, A. B. (1977) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-45-4-768 · Cited by 227 · see citing works
Manda, K., Ueno, M., & Anzai, K. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00432.x · Cited by 222 · see citing works
Tan, D. X., Hardeland, R., Manchester, L. C., Pöeggeler, B., López‐Burillo, S., Mayo, J. C., Sainz, R. M., & Reiter, R. J. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00037.x · Cited by 212 · see citing works
Self-citationByeon, Y., & Back, K. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12111 · Cited by 209 · see citing works
Galano, A., Medina, M. E., Tan, D. X., & Reiter, R. J. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12196 · Cited by 200 · see citing works
Self-citationByeon, Y., Lee, H. Y., Lee, K., & Back, K. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12160 · Cited by 200 · see citing works
A meta-analysis on dose–response relationship between night shift work and the risk of breast cancer
Wang, F., Yeung, K.-W., Chan, W. C., Kwok, C. C.-H., Leung, S.-L., Wu, Ç., Chan, E. Y. Y., Yu, I. T.-S., Yang, X. R., & Tse, L. A. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt283 · Cited by 197 · see citing works
Gitto, E., Tan, D.-X., Reiter, R. J., Karbownik, M., Manchester, L. C., Cuzzocrea, S., Fulia, F., & Barberi, I. (2001) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357011777747 · Cited by 196 · see citing works
Self-citationTan, D.-X., Zheng, X., Kong, J., Manchester, L., Hardeland, R., Kim, S., Xu, X., & Reiter, R. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150915858 · Cited by 188 · see citing works
Self-citationKang, K., Lee, K., Park, S., Byeon, Y., & Back, K. (2012) · Journal of Pineal Research · doi:10.1111/jpi.12011 · Cited by 186 · see citing works
Melatonin: A Clock‐Output, A Clock‐Input
Stehle, J. H., von Gall, C., & Korf, H. (2003) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2003.01001.x · Cited by 181 · see citing works
Chemical stress by different agents affects the melatonin content of barley roots
Arnao, M. B., & Hernández‐Ruíz, J. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2008.00660.x · Cited by 181 · see citing works
Ganguly, S., Gastel, J. A., Weller, J. L., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141118798 · Cited by 181 · see citing works
Melatonin: Occurrence and daily rhythm in Chenopodium rubrum
Kolář, J., Macháčková, I., Eder, J., Prinsen, E., Dongen, W. V., Onckelen, H. A. V., & Illnerová, H. (1997) · Phytochemistry · doi:10.1016/s0031-9422(96)00568-7 · Cited by 179 · see citing works
Fontana, L., Klein, S., & Holloszy, J. O. (2009) · AGE · doi:10.1007/s11357-009-9118-z · Cited by 178 · see citing works
Melatonin as an antioxidant and its semi-lunar rhythm in green macroalga Ulva sp.
Paz-Tal, O., Haim, A., Harel, O., & Gerchman, Y. (2011) · Journal of Experimental Botany · doi:10.1093/jxb/erq378 · Cited by 177 · see citing works
Night shift work, chronotype and prostate cancer risk in the MCC‐ S pain case‐control study
Papantoniou, K., Castaño‐Vinyals, G., Espinosa, A., Aragonés, N., Pérez‐Gómez, B., Burgos, J., Gómez‐Acebo, I., Llorca, J., Peiró, R., Jiménez‐Moleón, J. J., et al. (2014) · International Journal of Cancer · doi:10.1002/ijc.29400 · Cited by 175 · see citing works
Cellular localization and kinetics of the rice melatonin biosynthetic enzymes SNAT and ASMT
Byeon, Y., Lee, H. Y., Lee, K., Park, S.-K., & Back, K. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12103 · Cited by 175 · see citing works
Rhythmic transcription: the molecular basis of circadian melatonin synthesis
Foulkes, N. S., Sassone‐Corsi, P., Borjigin, J., Snyder, S. H., & Snyder, S. H. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01109-0 · Cited by 173 · see citing works
Growth conditions determine different melatonin levels in L upinus albus L
Arnao, M. B., & Hernández‐Ruíz, J. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12055 · Cited by 169 · see citing works
Manchester, L. C., Pöeggeler, B., Alvares, F. L., Ogden, G. B., & Reiter, R. J. (1995) · PubMed · Cited by 165 · see citing works
Self-citationReiter, R. J., Tan, D. X., Kim, S. J., & Cruz, M. H. C. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0719-7 · Cited by 163 · see citing works
Self-citationMelatonin reduces lipid peroxidation and membrane viscosity
Reiter, R. J., Tan, D., & Galano, A. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00377 · Cited by 154 · see citing works
Self-citationElbe, H., Vardı, N., Eşrefoğlu, M., Ateş, B., Yoloğlu, S., & Taşkapan, Ç. (2014) · Human & Experimental Toxicology · doi:10.1177/0960327114531995 · Cited by 150 · see citing works
Lee, H. Y., Byeon, Y., Lee, K., et al. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12181 · Cited by 149 · see citing works
Reiter, R. J. (1986) · PubMed · Cited by 149 · see citing works
Self-citationLerner, A. B., & Case, J. D. (1959) · Journal of Investigative Dermatology · doi:10.1038/jid.1959.38 · Cited by 144 · see citing works
The Mel1a melatonin receptor gene is expressed in human suprachiasmatic nuclei
Weaver, D. R., & Reppert, S. M. (1996) · Neuroreport · doi:10.1097/00001756-199612200-00022 · Cited by 139 · see citing works
N‐acetyltransferase is not the rate‐limiting enzyme of melatonin synthesis at night
Liu, T., & Borjigin, J. (2005) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2005.00223.x · Cited by 135 · see citing works
Functional analyses of three ASMT gene family members in rice plants
Park, S., Byeon, Y., & Back, K. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12088 · Cited by 134 · see citing works
Melatonin Signaling Controls Circadian Swimming Behavior in Marine Zooplankton
Tosches, M. A., Bucher, D. B., Vopálenský, P., & Arendt, D. (2014) · Cell · doi:10.1016/j.cell.2014.07.042 · Cited by 134 · see citing works
MELATONIN IN THE RETINA OF RATS: A DIURNAL RHYTHM
Pang, S. F., Yu, H.-S., Suen, H. C., et al. (1980) · Journal of Endocrinology · doi:10.1677/joe.0.0870089 · Cited by 126 · see citing works
Determination of melatonin and its isomer in foods by liquid chromatography tandem mass spectrometry
Kocadağlı, T., Yılmaz, C., & Gökmen, V. (2013) · Food Chemistry · doi:10.1016/j.foodchem.2013.12.036 · Cited by 121 · see citing works
Vitalini, S., Gardana, C., Simonetti, P., Fico, G., & Iriti, M. (2012) · Journal of Pineal Research · doi:10.1111/jpi.12028 · Cited by 115 · see citing works
Byeon, Y., & Back, K. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12220 · Cited by 114 · see citing works
Janjetovic, Z., Nahmias, Z. P., Hanna, S., Jarrett, S. G., Kim, T., Reiter, R. J., & Slominski, A. T. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12146 · Cited by 113 · see citing works
Self-citationDecreased melatonin synthesis in patients with coronary artery disease
Sakotnik, A. (1999) · European Heart Journal · doi:10.1053/euhj.1999.1527 · Cited by 110 · see citing works
Tilden, A. R., Becker, M. A., Amma, L. L., Arciniega, J., & McGaw, A. K. (1997) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1997.tb00310.x · Cited by 108 · see citing works
Lei, Q., Wang, L., Tan, D. X., Zhao, Y. Q., Zheng, X., Chen, H., Li, Q., Zuo, B., & Kong, J. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12096 · Cited by 108 · see citing works
Self-citationJaworek, J. M., Leja‐Szpak, A., Bonior, J., Nawrot, K., Tomaszewska, R., Stachura, J., Sendur, R., Pawlik, W. W., Brzozowski, T., & Konturek, S. J. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.02937.x · Cited by 102 · see citing works
Manda, K., Ueno, M., & Anzai, K. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2008.00611.x · Cited by 101 · see citing works
Predominance of 2‐hydroxymelatonin over melatonin in plants
Byeon, Y., Tan, D. X., Reiter, R. J., & Back, K. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12274 · Cited by 101 · see citing works
Self-citationNight work and breast cancer in women: a Swedish cohort study
Åkerstedt, T., Knutsson, A., Narusyte, J., Svedberg, P., Kecklund, G., & Alexanderson, K. A. E. (2015) · BMJ Open · doi:10.1136/bmjopen-2015-008127 · Cited by 99 · see citing works
Melatonin in the multi‐oscillatory mammalian circadian world
Pévet, P., Agez, L., Bothorel, B., Saboureau, M., Gauer, F., Laurent, V., & Masson‐Pévet, M. (2006) · Chronobiology International · doi:10.1080/07420520500482074 · Cited by 98 · see citing works
Production of melatonin by Saccharomyces strains under growth and fermentation conditions
Rodriguez-Naranjo, M. I., Torija, M.-J., Mas, A., et al. (2012) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2012.00990.x · Cited by 96 · see citing works
Night Shift Work and Levels of 6-Sulfatoxymelatonin and Cortisol in Men
Mirick, D. K., Bhatti, P., Chen, C., Nordt, F. J., Stanczyk, F. Z., & Davis, S. (2013) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-12-1377 · Cited by 95 · see citing works
Brainard, G. C., Petterborg, L. J., Richardson, B. A., & Reiter, R. J. (2008) · Neuroendocrinology · doi:10.1159/000123405 · Cited by 94 · see citing works
Self-citationTan, D., Hardeland, R., Manchester, L. C., Galano, A., & Reiter, R. J. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666131129113146 · Cited by 92 · see citing works
Self-citationByeon, Y., Lee, K., Park, Y., Park, S., & Back, K. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12080 · Cited by 91 · see citing works
Mao, L., Dauchy, R. T., Blask, D. E., Slakey, L. M., Xiang, S., Yuan, L., Dauchy, E. M., Shan, B., Brainard, G. C., Hanifin, J. P., et al. (2012) · Molecular Endocrinology · doi:10.1210/me.2012-1071 · Cited by 90 · see citing works
Kelly, R. W., Amato, F., & Seamark, R. F. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(84)90732-0 · Cited by 86 · see citing works
Reiter, R. J., Rosales‐Corral, S., Coto‐Montes, A. M., Boga, J. A., Tan, D.-X., Davis, J. M., Konturek, P. C., Konturek, S. J., & Brzozowski, T. (2011) · PubMed · Cited by 81 · see citing works
Self-citationMetabolism of melatonin by cytochrome P450s in rat liver mitochondria and microsomes
Semak, I. V., Корик, Е. О., Antonova, M., Wortsman, J., & Slominski, A. T. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2008.00630.x · Cited by 80 · see citing works
A Serum Melatonin Rhythm in Chickens and Its Abolition by Pinealectomy1
Pelham, R. W. (1975) · Endocrinology · doi:10.1210/endo-96-2-543 · Cited by 78 · see citing works
Dibrova, D. V., Cherepanov, D. A., Galperin, M. Y., Skulachev, V. P., & Mulkidjanian, A. Y. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.07.006 · Cited by 76 · see citing works
Legros, C., Chesneau, D., Boutin, J. A., Barc, C., & Malpaux, B. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12134 · Cited by 73 · see citing works
Yu, H.-S., Pang, S. F., Tang, P. L., & Brown, G. M. (2008) · Neuroendocrinology · doi:10.1159/000123170 · Cited by 70 · see citing works
Park, S., Byeon, Y., & Back, K. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12053 · Cited by 69 · see citing works
Alcoholic fermentation induces melatonin synthesis in orange juice
Fernández‐Pachón, M., Medina, S., Herrero-Martín, G., Cerrillo, I., Berná, G., Escudero‐López, B., Ferreres, F., Martı́n, F., García-Parrilla, M. C., & Gil‐Izquierdo, Á. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12093 · Cited by 69 · see citing works
Emergence of naturally occurring melatonin isomers and their proposed nomenclature
Tan, D. X., Hardeland, R., Manchester, L. C., Rosales‐Corral, S., Coto‐Montes, A. M., Boga, J. A., & Reiter, R. J. (2012) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2012.00979.x · Cited by 68 · see citing works
Self-citationTheoretical insight into the antioxidant properties of melatonin and derivatives
Johns, J. R., & Platts, J. A. (2014) · Organic & Biomolecular Chemistry · doi:10.1039/c4ob01396d · Cited by 63 · see citing works
Domínguez‐Rodríguez, A., Abreu-González, P., Arroyo, E., & Reiter, R. J. (2012) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2012.01001.x · Cited by 59 · see citing works
Self-citationDrastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya
Falcón, J., Coon, S. L., Laurence Besseau, A., Cazaméa-Catalan, D., Fuentès, M., Magnanou, É., Paulin, C.-H., Bœuf, G., Sauzet, S., Jørgensen, E. H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312634110 · Cited by 59 · see citing works
Kołodziejczyk, I., Bałabusta, M., Szewczyk, R., et al. (2015) · Acta Physiologiae Plantarum · doi:10.1007/s11738-015-1850-7 · Cited by 55 · see citing works
Reiter, R. J. (2008) · Neuroendocrinology · doi:10.1159/000122222 · Cited by 55 · see citing works
Self-citationThe Role of Melatonin in Multiple Sclerosis, Huntington's Disease and Cerebral Ischemia
Escribano, B. M., Colín-González, A. L., Santamarı́a, A., & Túnez, I. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666140806160400 · Cited by 53 · see citing works
Tan, D., Manchester, L. C., Sainz, R. M., Mayo, J. C., León, J., & Reiter, R. J. (2005) · Endocrine · doi:10.1385/endo:27:2:149 · Cited by 53 · see citing works
Self-citationJohnston, J. D., Bashforth, R., Diack, A., et al. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.01.011 · Cited by 51 · see citing works
Oxenkrug, G. F., & McIntyre, I. M. (1985) · Life Sciences · doi:10.1016/0024-3205(85)90303-0 · Cited by 50 · see citing works
Troiani, M. E., Reiter, R. J., Vaughan, M. K., et al. (2008) · Neuroendocrinology · doi:10.1159/000124891 · Cited by 48 · see citing works
Self-citationDramatic Rises of Melatonin and 5-Methoxytryptamine in Gonyaulax Exposed to Decreased Temperature
Fuhrberg, B., Hardeland, R., Pöeggeler, B., & Behrmann, C. (1997) · Biological Rhythm Research · doi:10.1076/brhm.28.1.144.12978 · Cited by 45 · see citing works
Ceinos, R. M., Chansard, M., Revel, F., et al. (2004) · Neurosignals · doi:10.1159/000081966 · Cited by 44 · see citing works
Ortíz, G. G., Pacheco-Moisés, F. P., Gómez-Rodríguez, V. M., González-Renovato, E. D., Torres-Sánchez, E. D., & Anguiano, A. C. R. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-013-9416-0 · Cited by 43 · see citing works
Túnez, I., Muñoz, M. C., Medina-Fernández, F. J., Salcedo, M., Feijóo, M., & Montilla, P. (2005) · Cell Biochemistry and Function · doi:10.1002/cbf.1276 · Cited by 42 · see citing works
Sharma, S., & Haldar, C. (2006) · International Journal of Radiation Biology · doi:10.1080/09553000600774105 · Cited by 39 · see citing works
Formation of Melatonin and Its Isomer during Bread Dough Fermentation and Effect of Baking
Yılmaz, C., Kocadağlı, T., & Gökmen, V. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf500294b · Cited by 39 · see citing works
Pinealectomy blocks vernal courtship behavior in red-sided garter snakes
Nelson, R. J., Mason, R. T., Krohmer, R. W., et al. (1987) · Physiology & Behavior · doi:10.1016/0031-9384(87)90014-x · Cited by 38 · see citing works
‘Melatonin isomer’ in wine is not an isomer of the melatonin but tryptophan‐ethylester
Gardana, C., Iriti, M., Stuknytė, M., et al. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12183 · Cited by 33 · see citing works
Oxidation of melatonin by oxoferryl hemoglobin: A mechanistic study
Tesoriere, L., Avellone, G., Ceraulo̊, L., et al. (2001) · Free Radical Research · doi:10.1080/10715760100301161 · Cited by 32 · see citing works
Loss of intraventricular fluid melatonin can explain the neuropathology of Alzheimer's disease
MAURIZI, C. P. (1997) · Medical Hypotheses · doi:10.1016/s0306-9877(97)90220-6 · Cited by 30 · see citing works
Troiani, M. E., Reiter, R. J., Tannenbaum, M. G., et al. (1988) · Journal of Neural Transmission · doi:10.1007/bf01244781 · Cited by 29 · see citing works
Self-citationApplication of long-term microdialysis in circadian rhythm research
Borjigin, J., & Liu, T. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.10.010 · Cited by 28 · see citing works
Melatonin is formed during winemaking at safe levels of biogenic amines
Rodriguez-Naranjo, M. I., Ordóñez-Díaz, J. L., Callejón, R. M., Cantos‐Villar, E., & García-Parrilla, M. C. (2013) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.03.014 · Cited by 27 · see citing works
Lindén, J., Pohjanvirta, R., Rahko, T., et al. (1991) · Pharmacology & Toxicology · doi:10.1111/j.1600-0773.1991.tb01325.x · Cited by 26 · see citing works
Isorna, E., M’Rabet, A. E., Confente, F., et al. (2008) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2008.10.007 · Cited by 26 · see citing works
Pohjanvirta, R., Laitinen, J. T., Vakkuri, O., et al. (1996) · Toxicology · doi:10.1016/0300-483x(95)03241-7 · Cited by 25 · see citing works
Szewczuk, L. M., Tarrant, M. K., Sample, V., et al. (2008) · Biochemistry · doi:10.1021/bi801189d · Cited by 24 · see citing works
Isorna, E., Aliaga-Guerrero, M., M’Rabet, A. E., Servili, A., Falcón, J., & Muñoz‐Cueto, J. A. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00907.x · Cited by 23 · see citing works
Roopin, M., Yacobi, Y. Z., & Levy, O. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12046 · Cited by 23 · see citing works
TCDD Reduces Serum Melatonin Levels in Long‐Evans Rats
Pohjanvirta, R., Tuomisto, J., Lindén, J., et al. (1989) · Pharmacology & Toxicology · doi:10.1111/j.1600-0773.1989.tb01164.x · Cited by 22 · see citing works
Alteration in diurnal and nocturnal melatonin serum level in patients with chronic heart failure.
Dzida, G. J., Prystupa, A., Lachowska-Kotowska, P., Kadas, T., Kamieński, P., Kimak, E., Hałabiś, M., & Kiciński, P. (2013) · PubMed · Cited by 21 · see citing works
Endocrine and metabolic effects of life-long food restriction in rats
Stokkan, K., Reiter, R. J., Vaughan, M. K., et al. (1991) · European Journal of Endocrinology · doi:10.1530/acta.0.1250093 · Cited by 20 · see citing works
Self-citationLow temperature stimulates pineal activity in Syrian hamsters
Stokkan, K., Nonaka, K. O., Lerchl, A., et al. (1991) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1991.tb00008.x · Cited by 20 · see citing works
Delayed effect of pinealectomy on hibernation of the golden-mantled ground squirrel
Ralph, C. L., Harlow, H. J., & Phillips, J. A. (1982) · International Journal of Biometeorology · doi:10.1007/bf02219502 · Cited by 19 · see citing works
Computational Study on the Kinetics and Mechanism of the Carbaryl + OH Reaction
Zavala‐Oseguera, C., Galano, A., & Merino, G. (2014) · The Journal of Physical Chemistry A · doi:10.1021/jp507244s · Cited by 5 · see citing works
The effect of acute swimming exercise on plasma melatonin levels in rats
Uzun, A., Baltacı, A. K., Kilic, M., et al. (2012) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2012_015 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut
Vaccaro, A., Kaplan Dor, Y., Nambara, K., Pollina, E. A., Lin, C., Greenberg, M. E., & Rogulja, D. (2020) · Cell · doi:10.1016/j.cell.2020.04.049 · Cited by 541 · see citing works
Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas
Reiter, R. J., Rosales-Corral, S., Tan, D. X., Jou, M. J., Galano, A., & Xu, B. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2609-7 · Cited by 558 · see citing works
Self-citationMelatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics
Tan, D.-X., Manchester, L., Qin, L., & Reiter, R. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122124 · Cited by 402 · see citing works
Self-citationMelatonin as an anti-inflammatory agent modulating inflammasome activation
Favero, G., Franceschetti, L., Bonomini, F., Rodella, L. F., & Rezzani, R. (2017) · International Journal of Endocrinology · doi:10.1155/2017/1835195 · Cited by 233 · see citing works
Is Melatonin the Cornucopia of the 21st Century?
Ferlazzo, N., Andolina, G., Cannata, A., Costanzo, M. G., Rizzo, V., Currò, M., Ientile, R., & Caccamo, D. (2020) · Antioxidants · doi:10.3390/antiox9111088 · Cited by 189 · see citing works
Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
“Finally, melatonin is involved with multiple activities that include mitochondrial homeostasis, genomic regulation, modulation of inflammatory and immune cytokines, directly impacting both systemic and acute anti-inflammatory properties as well as indications around its potential role in phase separation [25,26].”
BackgroundMitochondria: the birth place, battle ground and the site of melatonin metabolism in cells
Tan, D.-X., & Reiter, R. J. (2019) · Melatonin Research · doi:10.32794/mr11250011 · Cited by 172 · see citing works
“was discussed in detail by two groups (60, 63).”
BackgroundSelf-citationIonizing Radiation as a Source of Oxidative Stress—The Protective Role of Melatonin and Vitamin D
Nuszkiewicz, J., Woźniak, A., & Szewczyk-Golec, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165804 · Cited by 156 · see citing works
Skobowiat, C., Brożyna, A. A., Janjetovic, Z., Jeayeng, S., Oak, A. S. W., Kim, T., Panich, U., Reiter, R. J., & Slominski, A. T. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12501 · Cited by 105 · see citing works
Self-citationThe Potential of Phytomelatonin as a Nutraceutical
B. Arnao, M., & Hernández-Ruiz, J. (2018) · Molecules · doi:10.3390/molecules23010238 · Cited by 102 · see citing works
Phenolic Melatonin-Related Compounds: Their Role as Chemical Protectors against Oxidative Stress
Galano, A., Castañeda-Arriaga, R., Pérez-González, A., Tan, D.-X., & Reiter, R. (2016) · Molecules · doi:10.3390/molecules21111442 · Cited by 60 · see citing works
Self-citationPan, S., Guo, Y., Hong, F., Xu, P., & Zhai, Y. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166281 · Cited by 37 · see citing works
Reiter, R. J., Sharma, R., Rosales-Corral, S., de Mange, J., Phillips, W. T., Tan, D. X., & Bitar, R. D. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.03.025 · Cited by 31 · see citing works
Self-citationLower Plasma Melatonin Levels Predict Worse Long-Term Survival in Pulmonary Arterial Hypertension
Cai, Z., Klein, T., Geenen, L. W., Tu, L., Tian, S., van den Bosch, A. E., de Rijke, Y. B., Reiss, I. K. M., Boersma, E., Duncker, D. J., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051248 · Cited by 17 · see citing works
- Authors
- Tan, D.-X., Manchester, L., Esteban-Zubero, E., Zhou, Z., & Reiter, R.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Department of Cellular and Structural Biology, Health Science Center, University of Texas, San Antonio, TX 78229, USA
- Corresponding author
- Tan, Dun-Xian
- Reiter, Russel
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2015-10-16
- Volume
- 20
- Issue
- 10
- Pages
- 18886-18906
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC6332205
- OpenAlex
- W1962181495
- Cited by
- 719
- References
- 138
- Citations by year
- 2026: 53 · 2025: 84 · 2024: 82 · 2023: 90 · 2022: 111 · 2021: 75 · 2020: 64 · 2019: 50 · 2018: 33 · 2017: 43 · 2016: 32 · 2015: 2
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melatonin, antioxidants, melatonin synthesis, melatonin metabolism, tryptophan metabolism, oxidative stress, free radical scavenging, cytochrome c, endosymbiosis, melatonin metabolites, endogenous antioxidants
- MeSH terms
- Animals, Antioxidants, Humans, Melatonin, Reactive Oxygen Species, Oxidative Stress, Reactive Nitrogen Species, Biosynthetic Pathways
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
