A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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=> gamma-glutamyltransferase (GGT)


GGT levels are elevated in COVID-19 (Li et al., 2020; Gu et al., 2020).

Li M, Dong Y, Wang H, Guo W, Zhou H, Zhang Z, Tian C, Du K, Zhu R, Wang L, Zhao L, Fan H, Luo S, Hu D - "Cardiovascular disease potentially contributes to the progression and poor prognosis of COVID-19" Nutr Metab Cardiovasc Dis S0939-4753(20)30134-4 (2020) doi: 10.1016/j.numecd.2020.04.013. Epub ahead of print. PMID: 32456948; PMCID: PMC7165120

Gu X, Li X, An X, Yang S, Wu S, Yang X, Wang H - "Elevated serum aspartate aminotransferase level identifies patients with coronavirus disease 2019 and predicts the length of hospital stay" J Clin Lab Anal - Jun 2:e23391 (2020) doi: 10.1002/jcla.23391. Epub ahead of print. PMID: 32488888


"Urine NAG and gamma-GT activities significantly increased in dental fluorosis people from area of 2.58 mg/L fluoride in drinking water and in those two groups from area of 4.51 mg/L fluoride in drinking water. Moreover, there existed an obvious dose-effect relationship between the drinking water fluoride concentration and NAG and gamma-GT activity."

(Liu et al., 2005)

Liu JL, Xia T, Yu YY, Sun XZ, Zhu Q, He W, Zhang M, Wang A - "The dose-effect relationship of water fluoride levels and renal damage in children" Wei Sheng Yan Jiu 34(3):287-8 (2005) Chinese. PMID: 16111031

Xiong X, Liu J, He W, Xia T, He P, Chen X, Yang K, Wang A - "Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children" Environ Res 103(1):112-6 (2007) doi: 10.1016/j.envres.2006.05.008. Epub 2006 Jul 10. PMID: 16834990

"The patients of skeletal fluorosis were examined and compared with 24 age-matched controls for their serum enzymes activities of creatine kinase (CK), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH) and alpha-amylase. The activity of CK and GGT was elevated significantly (p<0.001) in all age groups as compared to controls."

(Shashi & Kumar, 2008)

Shashi A, Kumar M - "Clinical and biochemical evaluation of blood serum enzymes in osteofluorosis" Asian Journal of Microbiology, Biotechnology and Environmental Sciences 11(3):647-651 (2008)

"...both compounds produced early lesions of kidney tubule demonstrated by an intense increase of urine gamma-glutamyl transferase (GGT)."

(Kassabi et al., 1981)

Kassabi M, Braun JP, Burgat-Sacaze V, Bénard P, Rico AG - "Comparison of sodium and stannous fluoride nephrotoxicity" Toxicol Lett 7(6):463-7 (1981) doi: 10.1016/0378-4274(81)90094-1. PMID: 6113698.

Kessabi M, Hamliri A, Braun JP, Rico AG - "Experimental acute sodium fluoride poisoning in sheep: renal, hepatic, and metabolic effects" Fundam Appl Toxicol 5(6 Pt 1):1025-33 (1994) doi: 10.1016/0272-0590(85)90139-3. PMID: 2868958


Induction of GGT is mediated through activation of the ERK and p38MAPK pathways (Zhang et al., 2003).
SEE: viewtopic.php?f=66&t=1914

Zhang H, Dickinson DA, Liu RM, Forman HJ - "4-Hydroxynonenal increases gamma-glutamyl transpeptidase gene expression through mitogen-activated protein kinase pathways" Free Radic Biol Med 38(4):463-71 (2003) doi: 10.1016/j.freeradbiomed.2004.10.031. PMID: 15649648; PMCID: PMC2801023


"Alteration of the antioxidant system in the hypo-/hyperthyroidism-induced rats was confirmed by the significant increase of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and a decline in glutathione (GSH) content in both tissues were detected in hyperthyroid group compared to controls."

(Messarah et al., 2011)

Messarah M, Saoudi M, Boumendjel A, Boulakoud MS, Feki AE - "Oxidative stress induced by thyroid dysfunction in rat erythrocytes and heart" Environ Toxicol Pharmacol 31(1):33-41 (2011) doi: 10.1016/j.etap.2010.09.003. Epub 2010 Sep 15. PMID: 21787667.

Cattani D, Goulart PB, Cavalli VL, Winkelmann-Duarte E, Dos Santos AQ, Pierozan P, de Souza DF, Woehl VM, Fernandes MC, Silva FR, Gonçalves CA, Pessoa-Pureur R, Zamoner A - "Congenital hypothyroidism alters the oxidative status, enzyme activities and morphological parameters in the hippocampus of developing rats" Mol Cell Endocrinol 375(1-2):14-26 (2013) doi: 10.1016/j.mce.2013.05.001. Epub 2013 May 18. PMID: 23693027

"Using molecular docking analysis, we found rT3 interaction with αvβ3 integrin receptors, nongenomically activating signaling pathways (PKA, CaMKII, p38MAPK) that restored GGT activity.

(Domingues et al., 2018)

Domingues JT, Cattani D, Cesconetto PA, Nascimento de Almeida BA, Pierozan P, Dos Santos K, Razzera G, Mena Barreto Silva FR, Pessoa-Pureur R, Zamoner A - "Reverse T3 interacts with αvβ3 integrin receptor and restores enzyme activities in the hippocampus of hypothyroid developing rats: Insight on signaling mechanisms" Mol Cell Endocrinol 470:281-294 (2018) doi: 10.1016/j.mce.2017.11.013. Epub 2017 Nov 16. PMID: 29155306
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