The protective effects of melatonin on organisms against the environmental pollutants of heavy metal and non-metal toxins
Melatonin and environmental pollutants
Abstract
Metal and non-metal toxins are primarily derived from the human industrial and agricultural activities. These toxins have substantially polluted our ecosystem and become a major threatening factor to our health. Metal or non-metal pollutants are highly toxic because they interact with biological macromolecules including DNA, proteins and membrane to induce oxidative stress. If they are not properly handled, these toxins will inevitably cause organ and tissue injuries in both animals and plants. To identify the effective remedies to detoxify these toxins becomes the urgent agenda for researchers. Accumulated evidence indicates that melatonin may be a suitable molecule for this purpose. Melatonin, a naturally occurring antioxidant, directly scavenges ROS or upregulates expressions of many antioxidant enzymes to indirectly reduces ROS. In addition, it also promotes the excretion of these metal or non-metal toxins from the body. The multiple protective mechanisms of melatonin effectively suppress the oxidative stress induced by the metal or non-metal toxins in animals or plants. Melatonin is an environmental-friendly molecule with low or none toxicity to animals or plants. It is a promising molecule which can be used to detoxify the environmental pollutants.
References
2. Venegas C, Garcia JA, Escames G et al. (2012) Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J. Pineal Res. 52: 217-227.
3. Acuna-Castroviejo D, Escames G, Venegas C et al. (2014) Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 71: 2997-3025.
4. Arnao MB, Hernandez-Ruiz J (2007) Melatonin in plants: more studies are necessary. Plant. Signal Behav. 2: 381-382.
5. Back K, Tan DX, Reiter RJ (2016) Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts. J. Pineal Res. 61: 426-437.
6. Drazen DL, Nelson RJ (2001) Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity. Neuroendocrinology 74: 178-184.
7. Galano A, Reiter RJ (2018) Melatonin and its metabolites vs oxidative stress: from individual actions to collective protection. J. Pineal Res. 65: e12514.
8. Poeggeler B, Saarela S, Reiter RJ et al. (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.
9. Doghramji K (2007) Melatonin and its receptors: a new class of sleep-promoting agents. J. Clin. Sleep Med. 3: S17-23.
10. Maestroni GJ (1998) The photoperiod transducer melatonin and the immune-hematopoietic system. J. Photochem. Photobiol. B 43: 186-192.
11. Li Y, Li J, Li S et al. (2015) Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK. Toxicol. Appl. Pharmacol. 286: 53-63.
12. Tamura H, Takasaki A, Taketani T et al. (2014) Melatonin and female reproduction. J. Obstet. Gynaecol. Res. 40: 1-11.
13. Talib WH (2018). Melatonin and cancer hallmarks. Molecules 23: pii: E518.
14. Cabeza J, Motilva V, Martin MJ et al. (2001) Mechanisms involved in gastric protection of melatonin against oxidant stress by ischemia-reperfusion in rats. Life Sci. 68: 1405-1415.
15. Zhang H, Wang L, Shi K et al. (2019). Apple tree flowering is mediated by low level of melatonin under the regulation of seasonal light signal. J. Pineal Res.: 66 :e12551.
16. Hernandez-Ruiz J, Cano A, Arnao MB (2004) Melatonin: a growth-stimulating compound present in lupin tissues. Planta 220: 140-144.
17. Arnao MB, Hernandez-Ruiz J (2009) Protective effect of melatonin against chlorophyll degradation during the senescence of barley leaves. J. Pineal Res. 46: 58-63.
18. Martinez-Campa C, Alonso-Gonzalez C, Mediavilla MD et al. (2006) Melatonin inhibits both ER alpha activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium. J. Pineal Res. 40: 291-296.
19. Rao MV, Chhunchha B (2010) Protective role of melatonin against the mercury induced oxidative stress in the rat thyroid. Food Chem. Toxicol. 48:7-10.
20. Cao Z, Fang Y, Lu Y et al. (2017) Melatonin alleviates cadmium-induced liver injury by inhibiting the TXNIP-NLRP3 inflammasome. J. Pineal Res. 62: doi: 10.1111/jpi.12389.
21. Li R, Luo X, Li L et al. (2016) The protective effects of melatonin against oxidative stress and inflammation induced by acute cadmium exposure in mice testis. Biol. Trace Elem. Res. 170: 152-164.
22. Mukherjee R, Banerjee S, Joshi N et al. (2011) A combination of melatonin and alpha lipoic acid has greater cardioprotective effect than either of them singly against cadmium-induced oxidative damage. Cardiovasc. Toxicol. 11: 78-88.
23. Li M, Pi H, Yang Z et al. (2016) Melatonin antagonizes cadmium-induced neurotoxicity by activating the transcription factor EB-dependent autophagy-lysosome machinery in mouse neuroblastoma cells. J. Pineal Res. 61: 353-369.
24. Burkhardt S, Reiter RJ, Tan DX et al. (2001) DNA oxidatively damaged by chromium(III) and H(2)O(2) is protected by the antioxidants melatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, resveratrol and uric acid. Int. J. Biochem. Cell Biol. 33: 775-783.
25. Alonso-Gonzalez C, Gonzalez A, Mazarrasa O et al. (2007) Melatonin prevents the estrogenic effects of sub-chronic administration of cadmium on mice mammary glands and uterus. J. Pineal Res. 42: 403-410.
26. Kim YO, Ahn YK, Kim JH (2000) Influence of melatonin on immunotoxicity of cadmium. Int. J. Immunopharmacol. 22: 275-284.
27. Alonso-Gonzalez C, Mediavilla D, Martinez-Campa C et al. (2008) Melatonin modulates the cadmium-induced expression of MT-2 and MT-1 metallothioneins in three lines of human tumor cells (MCF-7, MDA-MB-231 and HeLa). Toxicol. Lett. 181:190-195.
28. McCarty MF (2012) Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure. Med. Hypotheses 79: 642-648.
29. Guo P, Pi H, Xu S et al. (2014) Melatonin improves mitochondrial function by promoting MT1/SIRT1/PGC-1 alpha-dependent mitochondrial biogenesis in cadmium-induced hepatotoxicity in vitro. Toxicol. Sci. 142: 182-195.
30. Xu S, Pi H, Zhang L et al. (2016) Melatonin prevents abnormal mitochondrial dynamics resulting from the neurotoxicity of cadmium by blocking calcium-dependent translocation of Drp1 to the mitochondria. J. Pineal Res. 60: 291-302.
31. Gu Q, Chen Z, Yu X et al. (2017) Melatonin confers plant tolerance against cadmium stress via the decrease of cadmium accumulation and reestablishment of microRNA-mediated redox homeostasis. Plant Sci. 261: 28-37.
32. Karbownik M, Gitto E, Lewinski A et al. (2001) Induction of lipid peroxidation in hamster organs by the carcinogen cadmium: melioration by melatonin. Cell Biol. Toxicol. 17: 33-40.
33. Cano P, Poliandri AH, Jimenez V et al. (2007) Cadmium-induced changes in Per 1 and Per 2 gene expression in rat hypothalamus and anterior pituitary: effect of melatonin. Toxicol. Lett. 172:131-136.
34. El-Sokkary GH, Nafady AA, Shabash EH (2010) Melatonin administration ameliorates cadmium-induced oxidative stress and morphological changes in the liver of rat. Ecotoxicol. Environ. Saf. 73: 456-463.
35. Mitra E, Bhattacharjee B, Pal PK et al. Melatonin protects against cadmium-induced oxidative damage in different tissues of rat: a mechanistic insight. Melatonin Res. 2: 1-21.
36. Romero A, Ramos E, de Los Rios C et al. (2014) A review of metal-catalyzed molecular damage: protection by melatonin. J. Pineal Res. 56: 343-370.
37. Patel TA, Rao MV (2015) Ameliorative effect of certain antioxidants against mercury induced genotoxicity in peripheral blood lymphocytes. Drug Chem. Toxicol. 38: 408-414.
38. Rao MV, Purohit A, Patel T (2010) Melatonin protection on mercury-exerted brain toxicity in the rat. Drug Chem. Toxicol. 33: 209-216.
39. Jindal M, Garg GR, Mediratta PK et al. (2011) Protective role of melatonin in myocardial oxidative damage induced by mercury in murine model. Hum. Exp. Toxicol. 30: 1489-1500.
40. Stacchiotti A, Bonomini F, Favero G et al. (2010) Stress proteins in experimental nephrotoxicity: a ten year experience. Ital. J. Anat. Embryol. 115: 153-158.
41. Rao MV, Gangadharan B (2008) Antioxidative potential of melatonin against mercury induced intoxication in spermatozoa in vitro. Toxicol. In Vitro 22: 935-942.
42. Sener G, Sehirli AO, Ayanoglu-Dulger G (2003) Melatonin protects against mercury(II)-induced oxidative tissue damage in rats. Pharmacol. Toxicol. 93: 290-296.
43. Mohandas G, Rao SV, Muralidhara et al. (2017) Whey protein isolate enrichment attenuates manganese-induced oxidative stress and neurotoxicity in drosophila melanogaster: relevance to parkinson's disease. Biomed. Pharmacother. 95: 1596-1606.
44. Sarkar S, Malovic E, Harischandra DS et al. (2018) Manganese exposure induces neuroinflammation by impairing mitochondrial dynamics in astrocytes. Neurotoxicology 64: 204-218.
45. Wang D, Zhang J, Jiang W et al. (2017) The role of NLRP3-CASP1 in inflammasome-mediated neuroinflammation and autophagy dysfunction in manganese-induced, hippocampal-dependent impairment of learning and memory ability. Autophagy 13: 914-927.
46. Gorojod RM, Alaimo A, Porte Alcon S et al. (2017) Interplay between iysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells. Arch. Toxicol. 91: 3065-3078.
47. Chen P, Culbreth M, Aschner M (2016) Exposure, epidemiology, and mechanism of the environmental toxicant manganese. Environ. Sci. Pollut. Res. Int. 23: 13802-13810.
48. Giordano G, Pizzurro D, VanDeMark K et al. (2009) Manganese inhibits the ability of astrocytes to promote neuronal differentiation. Toxicol. Appl. Pharmacol. 240: 226-235.
49. Deng Y, Jiao C, Mi C et al. (2015) Melatonin inhibits manganese-induced motor dysfunction and neuronal loss in mice: involvement of oxidative stress and dopaminergic neurodegeneration. Mol. Neurobiol. 51: 68-88.
50. Deng Y, Zhu J, Mi C et al. (2015) Melatonin antagonizes Mn-induced oxidative injury through the activation of keap1-Nrf2-ARE signaling pathway in the striatum of mice. Neurotox. Res. 27: 156-171.
51. Park E, Chun HS (2017) Melatonin attenuates manganese and lipopolysaccharide-induced inflammatory activation of BV2 microglia. Neurochem. Res. 42: 656-666.
52. Franklin M, Odontiadis J (2003) Effects of treatment with chromium picolinate on peripheral amino acid availability and brain monoamine function in the rat. Pharmacopsychiatry 36: 176-180.
53. Qi W, Reiter RJ, Tan DX et al. (2000) Increased levels of oxidatively damaged DNA induced by chromium(III) and H2O2: protection by melatonin and related molecules. J. Pineal Res. 29: 54-61.
54. Banerjee S, Joshi N, Mukherjee R et al. (2017) Melatonin protects against chromium (VI) induced hepatic oxidative stress and toxicity: duration dependent study with realistic dosage. Interdiscip. Toxicol. 10: 20-29.
55. Lv Y, Zhang P, Guo J et al. (2018) Melatonin protects mouse spermatogonial stem cells against hexavalent chromium-induced apoptosis and epigenetic histone modification. Toxicol. Appl. Pharmacol. 340: 30-38.
56. Susa N, Ueno S, Furukawa Y et al. (1997) Potent protective effect of melatonin on chromium(VI)-induced DNA single-strand breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat hepatocytes. Toxicol. Appl. Pharmacol. 144: 377-384.
57. Reiter RJ (1999) Oxidative damage to nuclear DNA: amelioration by melatonin. NEL Review. Neuro. Endocrinol. Lett. 20: 145-150.
58. Boguszewska A, Pasternak K (2004) Melatonin and bio-elements. Pol. Merkur. Lekarski. 17: 528-529.
59. Navarro-Alarcon M, Ruiz-Ojeda FJ, Blanca-Herrera RM et al. (2014) Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats. Food & function 5: 512-516.
60. Qi W, Reiter RJ, Tan DX et al. (2000) Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E. Environ. Health Perspect. 108: 399-402.
61. Karbownik M, Garcia JJ, Lewinski A et al. (2001) Carcinogen-induced, free radical-mediated reduction in microsomal membrane fluidity: reversal by indole-3-propionic acid. J. Bioenerg. Biomembr. 33: 73-78.
62. Zhang Y, Wei Z, Liu W et al. (2017) Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway. Oncotarget 8: 3773-3780.
63. Pal S, Chatterjee AK (2006) Possible beneficial effects of melatonin supplementation on arsenic-induced oxidative stress in Wistar rats. Drug Chem. Toxicol. 29: 423-433.
64. Soto-Arredondo KJ, Robles J, Diaz-Cervantes E et al. (2018) Effects of lead and lead-melatonin exposure on protein and gene expression of metal transporters, proteins and the copper/zinc ratio in rats. Biometals 31: 859-871.
65. Flora SJ, Flora G, Saxena G et al. (2007) Arsenic and lead induced free radical generation and their reversibility following chelation. Cell. Mol. Biol. (Noisy-le-grand) 53: 26-47.
66. Bazrgar M, Goudarzi I, Lashkarbolouki T et al. (2015) Melatonin ameliorates oxidative damage induced by maternal lead exposure in rat pups. Physiol. Behav. 151: 178-188.
67. Ustundag A, Duydu Y (2007) The influence of melatonin and N-acetylcysteine in delta-aminolevulinic acid and lead induced genotoxicity in lymphocytes in vitro. Biol. Trace Elem. Res. 117: 53-64.
68. Martinez-Alfaro M, Ramirez-Garcia G, Gutierrez-Granados S et al. (2013) Melatonin attenuates the effects of sub-acute administration of lead on kidneys in rats without altering the lead-induced reduction in nitric oxide. J. Trace Elem. Med. Biol. 27: 364-369.
69. Martinez-Alfaro M, Hernandez-Cortes D, Wrobel K et al. (2012) Effect of melatonin administration on DNA damage and repair responses in lymphocytes of rats subchronically exposed to lead. Mutat. Res. 742: 37-42.
70. Soleimani E, Goudarzi I, Abrari K et al. (2017) Maternal administration of melatonin prevents spatial learning and memory deficits induced by developmental ethanol and lead co-exposure. Physiol. Behav. 173: 200-208.
71. Hernandez-Plata E, Quiroz-Compean F, Ramirez-Garcia G et al. (2015) Melatonin reduces lead levels in blood, brain and bone and increases lead excretion in rats subjected to subacute lead treatment. Toxicol. Lett. 233: 78-83.
72. Suresh C, Dennis AO, Heinz J et al. (2006) Melatonin protection against lead-induced changes in human neuroblastoma cell cultures. Int. J. Toxicol. 25: 459-464.
73. Olayaki LA, Alagbonsi IA, Abdulrahim AH et al. (2018) Melatonin prevents and ameliorates lead-induced gonadotoxicity through antioxidative and hormonal mechanisms. Toxicol. Ind. Health 34: 596-608.
74. Cao XJ, Wang M, Chen WH et al. (2009) Effects of chronic administration of melatonin on spatial learning ability and long-term potentiation in lead-exposed and control rats. Biomed. Environ. Sci. 22: 70-75.
75. Flora SJ, Bhadauria S, Kannan GM et al. (2007) Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review. J. Environ. Biol. 28: 333-347.
76. Bali I, Bilir B, Emir S et al. (2016) The effects of melatonin on liver functions in arsenic-induced liver damage. Ulusal. cerrahi. dergisi. 32: 233-237.
77. Wang H, Xi S, Xu Y et al. (2013) Sodium arsenite induces cyclooxygenase-2 expression in human uroepithelial cells through MAPK pathway activation and reactive oxygen species induction. Toxicol. In Vitro 27: 1043-1048.
78. Dutta S, Saha S, Mahalanobish S et al. (2018) Melatonin attenuates arsenic induced nephropathy via the regulation of oxidative stress and inflammatory signaling cascades in mice. Food Chem. Toxicol. 118: 303-316.
79. Uygur R, Aktas C, Caglar V et al. (2016) Protective effects of melatonin against arsenic-induced apoptosis and oxidative stress in rat testes. Toxicol. Ind. Health 32: 848-859.
80. Pal S, Chatterjee AK (2005) Prospective protective role of melatonin against arsenic-induced metabolic toxicity in Wistar rats. Toxicology 208: 25-33.
81. Pant HH, Rao MV (2010) Evaluation of in vitro anti-genotoxic potential of melatonin against arsenic and fluoride in human blood cultures. Ecotoxicol. Environ. Saf. 73: 1333-1337.
82. Nooshinfar E, Bashash D, Safaroghli-Azar A et al. (2016) Melatonin promotes ATO-induced apoptosis in MCF-7 cells: proposing novel therapeutic potential for breast cancer. Biomed. Pharmacother. 83: 456-465.
83. Durappanavar PN, Nadoor P, Waghe P et al. (2019) Melatonin ameliorates neuropharmacological and neurobiochemical alterations induced by subchronic exposure to arsenic in Wistar rats. Biol. Trace Elem. Res. 190: 124-139.
84. Liu S, Wang F, Yan L et al. (2013) Oxidative stress and MAPK involved into ATF2 expression in immortalized human urothelial cells treated by arsenic. Arch. Toxicol. 87: 981-989.
85. Yun SM, Woo SH, Oh ST et al. (2016) Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells. Mol. Cell. Endocrinol. 422: 64-73.
86. Yu Z, Tian X, Peng Y et al. (2018) Mitochondrial cytochrome P450 (CYP) 1B1 is responsible for melatonin-induced apoptosis in neural cancer cells. J. Pineal Res. 65: e12478.
87. Tan D-X, Reiter R (2019) Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells. Melatonin Res. 2: 44-66.
88. Yellon SM, Singh D, Garrett TM et al. (2000) Reproductive, neuroendocrine, and immune consequences of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Siberian hamster. Biol. Reprod. 63: 538-543.
89. Sorg O, Zennegg M, Schmid P et al. (2009) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites. Lancet 374: 1179-1185.
90. Kakizuka S, Takeda T, Komiya Y et al. (2015) Dioxin-produced alteration in the profiles of fecal and urinary metabolomes: a change in bile acids and its relevance to toxicity. Biol. Pharm. Bull. 38: 1484-1495.
91. Pesonen M, Korkalainen M, Laitinen JT et al. (2000) 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters melatonin metabolism in fish hepatocytes. Chem. Biol. Interact. 126: 227-240.
92. Pohjanvirta R, Laitinen J, Vakkuri O et al. (1996) Mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces circulating melatonin levels in the rat. Toxicology 107: 85-97.
93. Linden J, Pohjanvirta R, Rahko T et al. (1991) TCDD decreases rapidly and persistently serum melatonin concentration without morphologically affecting the pineal gland in TCDD-resistant han/Wistar rats. Pharmacol. Toxicol. 69: 427-432.
94. Tan DX, Manchester LC, Terron MP et al. (2007) One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal Res. 42: 28-42.
95. Sarihan ME, Parlakpinar H, Ciftci O et al. (2015) Protective effects of melatonin against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cardiac injury in rats. Eur. J. Pharmacol. 762: 214-220.
96. Ilhan S, Atessahin D, Atessahin A et al. (2015) 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced hypertension: the beneficial effects of melatonin. Toxicol. Ind. Health 31: 298-303.
97. Songur A, Ozen OA, Sarsilmaz M (2010) The toxic effects of formaldehyde on the nervous system. Rev. Environ. Contam. Toxicol. 203: 105-118.
98. Mei Y, Duan C, Li X et al. (2016) Reduction of endogenous melatonin accelerates cognitive decline in mice in a simulated occupational formaldehyde exposure environment. Int. J. Environ. Res. Public Health 13: pii: E258.
99. Zararsiz I, Kus I, Ogeturk M et al. (2007) Melatonin prevents formaldehyde-induced neurotoxicity in prefrontal cortex of rats: an immunohistochemical and biochemical study. Cell Biochem. Funct. 25: 413-418.
100. Kang J, Duan J, Song J et al. (2018) Exposure to a combination of formaldehyde and DINP aggravated asthma-like pathology through oxidative stress and NF-kappaB activation. Toxicology 404-405: 49-58.
101. Duan J, Kang J, Qin W et al. (2018) Exposure to formaldehyde and diisononyl phthalate exacerbate neuroinflammation through NF-kappaB activation in a mouse asthma model. Ecotoxicol. Environ. Saf. 163: 356-364.
102. Ozen OA, Kus MA, Kus I et al. (2008) Protective effects of melatonin against formaldehyde-induced oxidative damage and apoptosis in rat testes: an immunohistochemical and biochemical study. Syst. Biol. Reprod. Med. 54:169-176.
103. Jaszczak E, Polkowska Z, Narkowicz S et al. (2017) Cyanides in the environment-analysis-problems and challenges. Environ. Sci. Pollut. Res. Int. 24: 15929-15948.
104. Tan DX, Manchester LC, Qin L et al. (2016) Melatonin: a mitochondrial targeting molecule involving mitochondrial protection and dynamics. Int. J. Mol. Sci. 17: pii: E2124.
105. Reiter RJ, Manchester LC, Tan DX (2010) Neurotoxins: free radical mechanisms and melatonin protection. Curr. Neuropharmacol. 8: 194-210.
106. Reiter RJ R-CS, Zhou X, Tan DX (2017) Role of SIRT3/SOD2 signaling in mediating the antioxidant actions of melatonin in mitochondria. Curr. Trends Endocrinol. 9: 45-49.
107. Dong Y, Zhang W, Lai B et al. (2012) Two free radical pathways mediate chemical hypoxia-induced glutamate release in synaptosomes from the prefrontal cortex. Biochim. Biophys. Acta 1823: 493-504.
108. Maharaj DS, Walker RB, Glass BD et al. (2003) 6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain homogenates. J. Chem. Neuroanat. 26: 103-107.
109. Martin M, Macias M, Leon J et al. (2002) Melatonin increases the activity of the oxidative phosphorylation enzymes and the production of ATP in rat brain and liver mitochondria. Int. J. Biochem. Cell Biol. 34:348-357.
110. Choi WI, Han SZ (2002) Effects of melatonin on KCN-induced neurodegeneration in mice. Int. J. Neurosci. 112:187-194.
111. Yamamoto H, Tang HW (1996) Preventive effect of melatonin against cyanide-induced seizures and lipid peroxidation in mice. Neurosci. Lett. 207: 89-92.
112. Yamamoto HA, Mohanan PV (2002) Melatonin attenuates brain mitochondria DNA damage induced by potassium cyanide in vivo and in vitro. Toxicology 179: 29-36.
113. Bavithra S, Selvakumar K, Krishnamoorthy G et al. (2013) Melatonin attenuates polychlorinated biphenyls induced apoptosis in the neuronal cells of cerebral cortex and cerebellum of adult male rats--in vivo. Environ. Toxicol. Pharmacol. 36: 152-163.
114. Bavithra S, Sugantha Priya E, Selvakumar K et al. (2015) Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)-Exposed Adult Male Rats. Neurochem. Res. 40: 1858-1869.
115. Venkataraman P, Krishnamoorthy G, Vengatesh G et al. (2008) Protective role of melatonin on PCB (Aroclor 1,254) induced oxidative stress and changes in acetylcholine esterase and membrane bound ATPases in cerebellum, cerebral cortex and hippocampus of adult rat brain. Int. J. Dev. Neurosci. 26: 585-591.
116. Venkataraman P, Krishnamoorthy G, Selvakumar K et al. (2009) Oxidative stress alters creatine kinase system in serum and brain regions of polychlorinated biphenyl (Aroclor 1254)-exposed rats: protective role of melatonin. Basic Clin. Pharmacol. Toxicol. 105: 92-97.
117. Venkataraman P, Selvakumar K, Krishnamoorthy G et al. (2010) Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats. Neurosci. Res. 66: 189-197.
118. Bavithra S, Selvakumar K, Sundareswaran L et al. (2017) Neuroprotective effect of melatonin against PCBs induced behavioural, molecular and histological changes in cerebral cortex of adult male Wistar rats. Neurochem. Res. 42:428-438.
119. Tan DX, Hardeland R, Manchester LC et al. (2012) Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science. J. Exp. Bot. 63: 577-597.
120. Zheng X, Tan DX, Allan AC et al. (2017) Chloroplastic biosynthesis of melatonin and its involvement in protection of plants from salt stress. Sci. Rep. 7: 41236.
121. Lee K, Choi GH, Back K (2017) Cadmium-induced melatonin synthesis in rice requires light, hydrogen peroxide, and nitric oxide: key regulatory roles for tryptophan decarboxylase and caffeic acid O-methyltransferase. J. Pineal Res. 63: doi: 10.1111/jpi.12441.
122. Lee HY, Back K (2017) Cadmium disrupts subcellular organelles, including chloroplasts, resulting in melatonin induction in plants. Molecules 22: pii: E1791.
123. Arnao M, Hernández-Ruiz J Melatonin and reactive oxygen and nitrogen species: a model for the plant redox network. Melatonin Res. 2: 152-168.
124. Wang M, Duan S, Zhou Z et al. (2019) Foliar spraying of melatonin confers cadmium tolerance in Nicotiana tabacum L. Ecotoxicol. Environ. Saf. 170: 68-76.
125. Hasan MK, Ahammed GJ, Sun S et al. (2019) Melatonin inhibits cadmium translocation and enhances plant tolerance by regulating sulfur uptake and assimilation in solanum lycopersicum L. J. Agric. Food Chem. 67:10563-10576.
126. Kaya C, Okant M, Ugurlar F et al. (2019)Melatonin-mediated nitric oxide improves tolerance to cadmium toxicity by reducing oxidative stress in wheat plants. Chemosphere 225:627-638.
127. Kobylinska A, Reiter RJ, Posmyk MM (2017) Melatonin protects cultured tobacco cells against lead-induced cell death via inhibition of cytochrome c translocation. Front. plant sci. 8: 1560.
128. Okant M, Kaya C (2019) The role of endogenous nitric oxide in melatonin-improved tolerance to lead toxicity in maize plants. Environ. Sci. Pollut. Res. Int. 26:11864-11874.
129. Xalxo R, Keshavkant S (2019) Melatonin, glutathione and thiourea attenuates lead and acid rain-induced deleterious responses by regulating gene expression of antioxidants in Trigonella foenum graecum L. Chemosphere 221:1-10.
130. Shah AA, Ahmed S, Ali A et al. (243) 2-Hydroxymelatonin mitigates cadmium stress in cucumis sativus seedlings: Modulation of antioxidant enzymes and polyamines. Chemosphere 243:125308.
131. Sun CK, Chen CH, Chang CL et al. (2017). Melatonin treatment enhances therapeutic effects of exosomes against acute liver ischemia-reperfusion injury. Am. J. Transl. Res. 9: 1543-1560.
132. Wang Y, Zeng S (2018) Melatonin promotes ubiquitination of phosphorylated pro-apoptotic protein bcl-2-interacting mediator of cell death-extra long (BimEL) in porcine granulosa cells. Int. J. Mol. Sci. 19: pii: E3431.
133. Fang Y, Deng S, Zhang J et al. (2018) Melatonin-mediated development of ovine cumulus cells, perhaps by regulation of DNA methylation. Molecules 23: pii: E494.
134. Mehrzadi S, Safa M, Kamrava SK et al. (2017) Protective mechanisms of melatonin against hydrogen-peroxide-induced toxicity in human bone-marrow-derived mesenchymal stem cells. Can. J. Physiol. Pharmacol. 95: 773-786.
135. Kocak N, Donmez H, Yildirim IH (2018) Effects of melatonin on apoptosis and cell differentiation in MCF-7 derived cancer stem cells. Cell. Mol. Biol. (Noisy-le-grand) 64: 56-61.
136. Liu H, Xu L, Wei JE et al. (2011) Role of CD4+ CD25+ regulatory T cells in melatonin-mediated inhibition of murine gastric cancer cell growth in vivo and in vitro. Anat. Rec. 294: 781-788.
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.