PFAS

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

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PFAS
©2020 PFPC

Recently, there has been much discussion about the association of disease severity in COVID-19 and exposure to PFAS (STEEP, 2020).

A study by Wu et al. (2020) has shown an association with TH17 and the AGE/RAGE pathways. Gq/11 proteins negatively control the differentiation of Th17 cells.
COVID-19

STEEP - "Pressure builds to study PFAS, COVID-19 link" (2020)
https://web.uri.edu/steep/pressure-buil ... d-19-link/

Wu Q, Xavier Coumoul X, Grandjean P, Barouki R, Audouze K - "Endocrine disrupting chemicals and COVID-19 relationships: a computational systems biology approach" (Under Peer-Review) (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373141/

Fluoride

PFAS are fluorinated chemicals - organic fluoride compounds. German research from the 1930s and 1940s brought evidence that all fluoride compounds - inorganic or organic - were able to influence thyroid hormone metabolism. This was well known to US toxicologists already in 1946. [SEE: Hodge Memo - https://www.poisonfluoride.com/pfpc/htm ... _1946.html ]

Current evidence of this can be seen by comparing effects on bone. Fluoride, TSH and PFOA all show identical effects on osteocalcin in bone. Effects are biphasic, a hallmark of TSH-mediated G protein activation. The G/q11 pathway is the calcium-transducing pathway.

Koskela A, Finnilä MA, Korkalainen M, Spulber S, Koponen J, Håkansson H, Tuukkanen J, Viluksela M - "Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation" Toxicol Appl Pharmacol 301:14-21 (2016)
https://pubmed.ncbi.nlm.nih.gov/27068293/

"In osteoblasts, low concentrations of PFOA increased osteocalcin (OCN) expression and calcium secretion, but at PFOA concentrations of 100μM and above osteocalcin (OCN) expression and calcium secretion were decreased. The number of osteoclasts was increased at all PFOA concentrations tested and resorption activity dose-dependently increased from 0.1-1.0μM, but decreased at higher concentrations. The results show that PFOA accumulates in bone and is present in bones until the old age. PFOA has the potential to influence bone turnover over a long period of time. Therefore bone is a target tissue for PFOA, and altered bone geometry and mineral density seem to persist throughout the life of the animal."

Gq/11

Gq/11 proteins are activated by TSH. The Gq/11 pathway controls thyroid hormone synthesis and iodide organification.

PFOA acts via Gq/11, as is demonstrated by its activation of phospholipase C and diacylglycerol in rat liver.

Reo NV, Narayanan L, Kling KB, Adinehzadeh M - "Perfluorodecanoic acid, a peroxisome proliferator, activates phospholipase C, inhibits CTP:phosphocholine cytidylyltransferase, and elevates diacylglycerol in rat liver" Toxicol Lett 86(1):1-11 (1996)
https://pubmed.ncbi.nlm.nih.gov/8685914/

Upham BL, Park JS, Babica P, Sovadinova I, Rummel AM, Trosko JE, Hirose A, Hasegawa R, Kanno J, Sai K - "Structure-activity-dependent regulation of cell communication by perfluorinated fatty acids using in vivo and in vitro model systems" Environ Health Perspect 117(4):545-51 (2009)
https://pubmed.ncbi.nlm.nih.gov/19440492/
"Inhibition of GJIC, in vitro, by PFOA depended on the activation of both ERK and phosphatidylcholine-specific phospholipase C (PC-PLC) in the dysregulation of GJIC in an oxidative-dependent mechanism."

Thyroid

PFOA exposure causes increased TSH levels. The increased level of TSH is observed as the most consistent outcome of PFAS exposure among generally exposed populations (Xi et al., 2020).

Byrne SC, Miller P, Seguinot-Medina S, Waghiyi V, Buck CL, von Hippel FA, Carpenter DO - "Exposure to perfluoroalkyl substances and associations with serum thyroid hormones in a remote population of Alaska Natives" Environ Res 166:537-543 (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932630/

Xie W, Zhong W, Appenzeller BMR, et al. - "Nexus between perfluoroalkyl compounds (PFCs) and human thyroid dysfunction: A systematic review evidenced from laboratory investigations and epidemiological studies" Critical Reviews in Environmental Science and Technology (2020)
https://www.tandfonline.com/doi/full/10 ... 20.1795052

SEE ALSO: FTOH and Dental Fluorosis
viewtopic.php?f=6&t=1581
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