Melatonin - Solutions

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.

Melatonin - Solutions

Postby admin » Fri May 22, 2020 6:20 pm

Melatonin
© 2020 PFPC

COVID-19

Martín Giménez VM, Inserra F, Tajer CD, Mariani J, Ferder L, Reiter RJ, Manucha W - "Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment" Life Sci 254:117808. (2020) doi: 10.1016/j.lfs.2020.117808. Epub ahead of print. PMID: 32422305; PMCID: PMC7227533
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227533/

Fluoride

Zhao J, Fu B, Peng W, Mao T, Wu H, Zhang Y - "Melatonin protect the development of preimplantation mouse embryos from sodium fluoride-induced oxidative injury" Environ Toxicol Pharmacol 54:133-141 (2017) doi: 10.1016/j.etap.2017.06.014. Epub 2017 Jun 29. PMID: 28728132.

Sana S, Ghosh S, Das N, Sarkar S, Mandal AK - "Vesicular melatonin efficiently downregulates sodium fluoride-induced rat hepato- and broncho-TNF-α, TGF-β expressions, and associated oxidative injury: a comparative study of liposomal and nanoencapsulated forms" Int J Nanomedicine 12:4059‐4071 (2017). Published 2017 May 29. doi:10.2147/IJN.S124119

Kumar J, Haldar C, Verma R - "Fluoride Compromises Testicular Redox Sensor, Gap Junction Protein, and Metabolic Status: Amelioration by Melatonin" Biol Trace Elem Res (2019) doi: 10.1007/s12011-019-01946-6. Epub ahead of print. PMID: 31828722
https://link.springer.com/article/10.10 ... 19-01946-6

Gq/11

"Melatonin activates two high-affinity G protein–coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer... The MT1 melatonin receptor couples to pertussis toxin–sensitive Gi and –insensitive Gq/11 G proteins and inhibits forskolin-stimulated cAMP, protein kinase A signaling, and CREB phosphorylation. The MT1 receptor also increases phosphorylation of mitogen-activated protein kinase 1/2 and extracellular signal–regulated kinase 1/2, as well as increasing potassium conductance through Kir inwardly rectifying channels... "


"However, melatonin transactivates the Gq pathway through MT2/5-HT2C heterodimers increasing inositol phosphate production. Interestingly, melatonin receptor antagonists, luzindole, and 4P-PDOT also transactivate the 5-HT2C receptor–mediated Gq pathway."


Liu J, Clough SJ, Hutchinson AJ, Adamah-Biassi EB, Popovska-Gorevski M, Dubocovich ML - "MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective" Annu Rev Pharmacol Toxicol 56:361-83 (2016) doi: 10.1146/annurev-pharmtox-010814-124742. Epub 2015 Oct 23. PMID: 26514204; PMCID: PMC5091650
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091650/

Lai L, Yuan L, Chen Q, Dong C, Mao L, Rowan B, Frasch T, Hill SM - "The Galphai and Galphaq proteins mediate the effects of melatonin on steroid/thyroid hormone receptor transcriptional activity and breast cancer cell proliferation" J Pineal Res 45(4):476-88 (2008) doi: 10.1111/j.1600-079X.2008.00620.x. Epub 2008 Aug 13. PMID: 18705646; PMCID: PMC4879591
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879591/

Zhao X, Sun J, Su W, Shan H, Zhang B, Wang Y, Shabanova A, Shan H, Liang H - "Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway" Int J Mol Sci 19(4):1118 (2018) doi: 10.3390/ijms19041118. PMID: 29642520; PMCID: PMC5979295
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979295/

Thyroid

Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeöld A, Bianco AC - "Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling" Endocr Rev 29(7):898-938 (2008) doi: 10.1210/er.2008-0019. Epub 2008 Sep 24. PMID: 18815314; PMCID: PMC2647704
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647704/

Lai L, Yuan L, Chen Q, Dong C, Mao L, Rowan B, Frasch T, Hill SM - "The Galphai and Galphaq proteins mediate the effects of melatonin on steroid/thyroid hormone receptor transcriptional activity and breast cancer cell proliferation" J Pineal Res 45(4):476-88 (2008) doi: 10.1111/j.1600-079X.2008.00620.x. Epub 2008 Aug 13. PMID: 18705646; PMCID: PMC4879591
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879591/

SEE: Melatonin/Gq/

"These results suggest that the protective effects of melatonin on lung disease are mainly mediated by a melatonin receptor."

Of special interest: a clinical trial about the use of melatonin in the prophylaxis of COVID-19 infection among healthcare workers is being carried out (ClinicalTrials.gov Identifier: #NCT04353128).
https://clinicaltrials.gov/ct2/show/NCT04353128
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