NRF2

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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NRF2

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NRF2
Nuclear factor erythroid 2-related factor 2
© 2021 PFPC


"NF-κB and Nrf2 pathways are involved in the cytokine storm and oxidative stress that are the hallmarks of COVID-19." (Bhandari et al., 2021)


COVID-19

Asiedu SO, Kwofie SK, Broni E, Wilson MD - "Computational Identification of Potential Anti-Inflammatory Natural Compounds Targeting the p38 Mitogen-Activated Protein Kinase (MAPK): Implications for COVID-19-Induced Cytokine Storm" Biomolecules 11(5):653 (2021)
https://pubmed.ncbi.nlm.nih.gov/33946644/

Bhandari R, Khanna G, Kaushik D, Kuhad A - "Divulging the Intricacies of Crosstalk Between NF-Kb and Nrf2-Keap1 Pathway in Neurological Complications of COVID-19" Mol Neurobiol 8:1–15 (2021)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938034/


Fluoride

Labib H, Badr AM, Abdelgwad M, Abd El-Galil TI - "KEAP1/Nrf2 pathway in sodium fluoride-induced cardiac toxicity and the prophylactic role of vitamin C versus platelet-rich plasma" Folia Morphol (Warsz). 2021 May 21. doi: 10.5603/FM.a2021.0053
https://pubmed.ncbi.nlm.nih.gov/34018173/
"The present study revealed that NaF administration caused histological alterations in the cardiac muscle and increased the accumulation of intracellular reactive oxygen species, the expression of iNOS and PCNA as well as collagen deposition in cardiac tissue. As supported by colorimetric analysis, an elevation in MDA level and a decrease in both SOD and TrX levels were seen, whereas molecular analysis revealed a decrease in Keap1 and an increase in Nrf2 and HO-1 gene expression."

Tang Z, Lai CC, Luo J, Ding YT, Chen Q, Guan ZZ - "Mangiferin prevents the impairment of mitochondrial dynamics and an increase in oxidative stress caused by excessive fluoride in SH-SY5Y cells" J Biochem Mol Toxicol 35(4):e22705 (2021) doi: 10.1002/jbt.22705. Epub 2021 Jan 4. PMID: 33393728
https://pubmed.ncbi.nlm.nih.gov/33393728/

Song C, Heping H, Shen Y, Jin S, Li D, Zhang A, Ren X, Wang K, Zhang L, Wang J, Shi D - "AMPK/p38/Nrf2 activation as a protective feedback to restrain oxidative stress and inflammation in microglia stimulated with sodium fluoride" Chemosphere 244:125495 (2020) doi: 10.1016/j.chemosphere.2019.125495. Epub 2019 Nov 27. PMID: 31837563
https://pubmed.ncbi.nlm.nih.gov/31837563/

Thangapandiyan S, Miltonprabu S - "Epigallocatechin gallate supplementation protects against renal injury induced by fluoride intoxication in rats: Role of Nrf2/HO-1 signaling" Toxicol Rep 1:12-30 (2014)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598207/

Gq/11

Espada S, Rojo AI, Salinas M, Cuadrado A - "The muscarinic M1 receptor activates Nrf2 through a signaling cascade that involves protein kinase C and inhibition of GSK-3beta: connecting neurotransmission with neuroprotection" J Neurochem 110(3):1107-19 (2009)
https://pubmed.ncbi.nlm.nih.gov/19558456/
"Luciferase reporter constructs for AREs and the use of two inhibitors of protein kinase C (PKC), chelerythrine and 2-aminoethyl diphenylborinate, or transfection with relevant expression vectors allowed us to identify Galphaq, phospholipase C-beta and the classical PKC-gamma isoenzyme, as responsible for the regulation of Nrf2."


Thyroid/TSH

Ziros PG, Renaud CO, Chartoumpekis DV, Bongiovanni M, Habeos IG, Liao XH, Refetoff S, Kopp PA, Brix K, Sykiotis GP - "Mice Hypomorphic for Keap1, a Negative Regulator of the Nrf2 Antioxidant Response, Show Age-Dependent Diffuse Goiter with Elevated Thyrotropin Levels" Thyroid 31(1):23-35 (2021)
https://pubmed.ncbi.nlm.nih.gov/32689903/
"Keap1KD mice develop age-dependent diffuse goiter with elevated TSH levels."

Aleksic M, Kalezic A, Saso L, Jankovic A, Korac B, Korac A - "The Unity of Redox and Structural Remodeling of Brown Adipose Tissue in Hypothyroidism" Antioxidants (Basel) 10(4):591 (2021)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068806/
"Hypothyroidism induced protein expression and nuclear translocation of a master regulator of redox-metabolic homeostasis, nuclear factor erythroid 2-related factor 2 (Nrf2), and an increased amount of 4-hydroxynonenal (4-HNE) protein adducts."

Mishra P, Paital B, Jena S, Swain SS, Kumar S, Yadav MK, Chainy GBN, Samanta L - "Possible activation of NRF2 by Vitamin E/Curcumin against altered thyroid hormone induced oxidative stress via NFĸB/AKT/mTOR/KEAP1 signalling in rat heart" Sci Rep 9(1):7408 (2019)
https://pubmed.ncbi.nlm.nih.gov/31092832/

Resveratrol

Wang J, Zhang Y, Hu S, Ge S, Jia M, Wang N - "Resveratrol inhibits MRGPRX2-mediated mast cell activation via Nrf2 pathway" Int Immunopharmacol. 93:107426 (2021)
https://pubmed.ncbi.nlm.nih.gov/33550032/

SEE: Resveratrol
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