Lead & Thyroid | Fluoride

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Lead & Thyroid | Fluoride

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Abdelouahab N, Mergler D, Takser L, Vanier C, St-Jean M, Baldwin M, Spear PA, Chan HM - "Gender differences in the effects of organochlorines, mercury, and lead on thyroid hormone levels in lakeside communities of Quebec (Canada)" Environ Res 107(3):380-92 (2008) doi: 10.1016/j.envres.2008.01.006
https://pubmed.ncbi.nlm.nih.gov/18313043/
(No relations were observed between T4 and any of the chemicals measured, but TSH was negatively related to blood Pb.)

Barysheva ES - "Experimental Simulation of the Effects of Essential and Toxic Trace Elements on Thyroid Function" Bull Exp Biol Med 164(4):439-441 (2018)
https://pubmed.ncbi.nlm.nih.gov/29500801/

Bledsoe ML, Pinkerton LE, Silver S, Deddens JA, Biagini REm - "Thyroxine and free thyroxine levels in workers occupationally exposed to inorganic lead" Environ Health Insights 5:55-61 (2011)
https://journals.sagepub.com/doi/pdf/10.4137/EHI.S7193
(Only T4 and FT4 measured, claims no effects...note race component!)

Cai D, Meng Z, Tang J, et al. - "A study on the change of levels of blood lead and serum biochemical parameters of the school age children from different areas" Prev Med 5:449-451 (2017) Center for Disease Control and Prevention, Zhejiang, China
T4 lower, TSH lower (all within "normal")...

Cai QL, Peng DJ, Lin-Zhao, Chen JW, Yong-Li, Luo HL, Ou SY, Huang ML, Jiang YM - "Impact of Lead Exposure on Thyroid Status and IQ Performance among School-age Children Living Nearby a Lead-Zinc Mine in China" Neurotoxicology 82:177-185 (2021)
https://www.sciencedirect.com/science/a ... 3X20301820
"Serum TSH levels and IQ of lead-intoxicated children were significantly lower than those without lead toxicity."

Chen A, Kim SS, Chung E, Dietrich KN. - "Thyroid hormones in relation to lead, mercury, and cadmium exposure in the National Health and Nutrition Examination Survey, 2007-2008" Environ Health Perspect 121(2):181-6 (2013)
doi: 10.1289/ehp.1205239.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569681/
(no actual values given to investigate ratios)

de Lima Junior NC, Camilo JF, do Carmo PR, de Andrade MN, Braz BF, Santelli RE, de Brito Gitirana L, Ferreira ACF, de Carvalho DP, Miranda-Alves L, Dias GRM - "Subacute exposure to lead promotes disruption in the thyroid gland function in male and female rats" Environ Pollut 274:115889 (2021)
https://pubmed.ncbi.nlm.nih.gov/33223335/

Doumouchtsis KK, Doumouchtsis SK, Doumouchtsis EK, Perrea DN - "The effect of lead intoxication on endocrine functions" J Endocrinol Invest 32(2):175-83 (2009). doi: 10.1007/BF03345710. PMID: 19411819.
"Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action."

Dundar B, Oktem F, Arslan MK, Delibas N, Baykal B, Arslan C, Gultepe M, Ilhan IE - "The effect of long-term low-dose lead exposure on thyroid function in adolescents" Environ Res 101(1):140-5 (2006)
https://pubmed.ncbi.nlm.nih.gov/16360141/
"This study revealed that long-term low-level lead exposure may lead to reduced FT4 level without significant changes in TSH and T3 levels in adolescents even at low Pb-B levels." Note: Study done in Isparta - fluoride/goiter region

Erfurth EM, Gerhardsson L, Nilsson A, Rylander L, Schütz A, Skerfving S, Börjesson J - "Effects of lead on the endocrine system in lead smelter workers" Arch Environ Health 56(5):449-55 (2001)
(claims no effects, TRH challenge test)

Fahim YA, Sharaf NE, Hasani IW, Ragab EA, Abdelhakim HK - "Assessment of Thyroid Function and Oxidative Stress State in Foundry Workers Exposed to Lead" J Health Pollut 10(27):200903 (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453815/
"The exposed group had significantly increased free triiodothyronine (FT3), free thyroxine (FT4) and significantly decreased thyroid stimulating hormone (TSH) (1.77±0.44 μIU/ml)...Workers exposed to Pb dust proved to be at risk for hyperthyroidism."

Goldman RH, White R, Kales SN, Hu H - "Lead poisoning from mobilization of bone stores during thyrotoxicosis" Am J Ind Med 25(3):417-24 (1994) 10.1002/ajim.4700250309. PMID: 8160659.
https://pubmed.ncbi.nlm.nih.gov/8160659/

Goldman M, Dillon RD - "Interaction of selenium and lead on several aspects of thyroid function in Pekin ducklings" Res Commun Chem Pathol Pharmacol 37(3):487-90 (1982)
https://pubmed.ncbi.nlm.nih.gov/7178658/
(Fact that selenium exerts protection points to deiodinase effects)

Horiguchi S, Endo G, Kiyota I - "Measurement of total triiodothyronine (T3), total thyroxine (T4) and thyroid-stimulating hormone (TSH) levels in lead-exposed workers" Osaka City Med J 33(1):51-6 (1987) PMID: 3431862.
https://pubmed.ncbi.nlm.nih.gov/3431862/

Huseman CA, Moriarty CM, Angle CR - "Childhood lead toxicity and impaired release of thyrotropin-stimulating hormone" Environ Res 42(2):524-33 (1987) doi: 10.1016/s0013-9351(87)80219-0. PMID: 3106028.
https://pubmed.ncbi.nlm.nih.gov/3106028/
(NOTE: Clear evdience of Gq/11 involvement as TRHr is ONLY coupled to Gq/11. Note reference to TH levels within "normal" range - disturbance of ratio clearly observable - action on deiodinase )

TABLE 3: Image

Ibrahim NM, Eweis EA, El-Beltagi HS, Abdel-Mobdy YE - "Effect of lead acetate toxicity on experimental male albino rat" Asian Pac J Trop Biomed 2(1):41-6 (2012) doi: 10.1016/S2221-1691(11)60187-1. PMID: 23569832; PMCID: PMC3609202
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609202/
T3, T4 were decreased..."Therefore, the present work advises people to prevent exposure to the lead compound to avoid injurious hazard risk."

Kahn LG, Liu X, Rajovic B, Popovac D, Oberfield S, Graziano JH, Factor-Litvak P - "Blood lead concentration and thyroid function during pregnancy: results from the Yugoslavia Prospective Study of Environmental Lead Exposure" Environ Health Perspect 122(10):1134-40 (2014) doi: 10.1289/ehp.1307669. Epub 2014 May 27. PMID: 24866691; PMCID: PMC4181923.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181923/
(Lower T4, higher TPOAb; no T3 or FT3 tested)

Klein M, Barbé F, Pascal V, Weryha G, Leclère J - "Lead poisoning secondary to hyperthyroidism: report of two cases" Eur J Endocrinol 138(2):185-8 (1998) doi: 10.1530/eje.0.1380185. PMID: 9506864.
https://pubmed.ncbi.nlm.nih.gov/9506864/

Liang QR, Liao RQ, Su SH, Huang SH, Pan RH, Huang JL - "Effects of lead on thyroid function of occupationally exposed workers" Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 21(2):111-3 (2003)
https://pubmed.ncbi.nlm.nih.gov/14761528/
(The workers with higher level of blood lead showed lower levels of T(3) and FT(3) than those with lower blood lead level.)

Rezaei M, Javadmoosavi SY, Mansouri B, Azadi NA, Mehrpour O, Nakhaee S - "Thyroid dysfunction: how concentration of toxic and essential elements contribute to risk of hypothyroidism, hyperthyroidism, and thyroid cancer" Environ Sci Pollut Res Int 26(35):35787-35796 (2019)
https://pubmed.ncbi.nlm.nih.gov/31701424/
"Logistic regression analysis showed that the effect of Cr, Co, Pb, Cu, Zn, and Cd was significant in developing hyperthyroidism and hypothyroidism; whereas, in patients with thyroid cancer, the effect of Cr, Cd, and Pb was found to be significant. In conclusion, our findings suggest that toxic metals such as Pb, Cd, and Cr can increase the risk of developing hypothyroidism and thyroid cancer, but more research is needed to evaluate the potential toxicity mechanisms of Pb, Cd, and Cr."

Robins JM, Cullen MR, Connors BB, Kayne RD - "Depressed thyroid indexes associated with occupational exposure to inorganic lead" Arch Intern Med 143(2):220-4 (1983) PMID: 6600605.
https://pubmed.ncbi.nlm.nih.gov/6600605/

Sandstead HH, Stant EG, Brill AB, Arias LI, Terry RT - "Lead intoxication and the thyroid" Arch Intern Med 123(6):632-5 (1969) PMID: 5771052
https://jamanetwork.com/journals/jamain ... act/575637

Schumacher C, Brodkin CA, Alexander B, Cullen M, Rainey PM, van Netten C, Faustman E, Checkoway H - "Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens" Int Arch Occup Environ Health 71(7):453-8 (1998)
https://pubmed.ncbi.nlm.nih.gov/9826077/
(Only T4 and TSH measured...claims no effects; see also Bledso, 2011)

Siegel M, Forsyth B, Siegel L, Cullen MR - "The effect of lead on thyroid function in children" Environ Res 49(2):190-6 (1989) doi: 10.1016/s0013-9351(89)80064-7. PMID: 2753005
https://pubmed.ncbi.nlm.nih.gov/8160659/]

Singh B, Chandran V, Bandhu HK, Mittal BR, Bhattacharya A, Jindal SK, Varma S - "Impact of lead exposure on pituitary-thyroid axis in humans" Biometals 13(2):187-92 (2000)
https://pubmed.ncbi.nlm.nih.gov/11016408/
"Interestingly, T3 was significantly lower with the longer (210 months) exposure time in comparison with the group having shorter (29 months) exposure duration. The mean TSH levels were significantly (p < 0.01) higher in workers exposed in comparison with the control group. This rise in TSH was independent of exposure time, but it was definitely associated with the Pb-B levels."

Singh B, Dhawan D - "Effect of lithium on thyroidal 131iodine uptake, its clearance, and circulating levels of triiodothyronine and thyroxine in lead-treated rats." Radiat Environ Biophys 38(4):261-6 (1999)
https://pubmed.ncbi.nlm.nih.gov/10654347/

Sun X, Liu W, Zhang B, Shen X, Hu C, Chen X, Jin S, Jiang Y, Liu H, Cao Z, Xia W, Xu S, Li Y - "Maternal Heavy Metal Exposure, Thyroid Hormones, and Birth Outcomes: A Prospective Cohort Study" J Clin Endocrinol Metab 104(11):5043-5052 (2019)
doi: 10.1210/jc.2018-02492. PMID: 30994896
https://academic.oup.com/jcem/article-l ... 2018-02492
"Urinary arsenic (As) and lead (Pb) had inverse relationships with FT3. We also observed the positive associations of maternal FT3 and FT3/FT4 ratio with birthweight. The mediation analyses suggested that 5.33% to 30.57% of the associations among V, As, and Pb levels and birth size might be mediated by maternal FT3 or FT3/FT4 ratio."

Wu CY, Liu B, Wang HL, Ruan DY - "Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats" Toxicol Appl Pharmacol 256(2):191-7 (2011)
https://pubmed.ncbi.nlm.nih.gov/21871911/

Yousif AS, Ahmed AA - "Effects of cadmium (Cd) and lead (Pb) on the structure and function of thyroid gland" Afr J Environ Sci Technol 3(3):78–85 (2009)
https://d1wqtxts1xzle7.cloudfront.net/4 ... 1467551687

Zadjali SA, Nemmar A, Fahim MA, Azimullah S, Subramanian D, Yasin J, Amir N, Hasan MY, Adem A - "Lead exposure causes thyroid abnormalities in diabetic rats" Int J Clin Exp Med 8(5):7160-7 (2015)
https://pubmed.ncbi.nlm.nih.gov/26221254/
("... caused an increase in thyroid stimulating hormone levels (P < 0.05) and reductions in thyroxine (P < 0.05) and triiodothyronine levels (P < 0.01), a clinical picture consistent with hypothyroidism.")

Zheng W, Shen H, Blaner WS, Zhao Q, Ren X, Graziano JH - "Chronic lead exposure alters transthyretin concentration in rat cerebrospinal fluid: the role of the choroid plexus" Toxicol Appl Pharmacol 139(2):445-50 (1996)
https://pubmed.ncbi.nlm.nih.gov/8806863/

Lead & Tooth Eruption (Regulated by TH)

Geng HO, Zhang JC, Zhou L, Cai HY, Wang JB - "The effect of lead exposure in utero on the teeth eruption and enamel development of rat offspring" Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 23(1):27-30 (2005) Chinese. PMID: 15748508
https://pubmed.ncbi.nlm.nih.gov/15748508/
  • Enamel

    Chen HS, Tsai YC, Chen KK, Tseng YC, Hsu KJ - "Detrimental effects of maternal lead exposure during pregnancy and lactation on molar development in the young rat" Bull Environ Contam Toxicol 89(2):240-4 (2012) doi: 10.1007/s00128-012-0683-y. Epub 2012 May 22. PMID: 22617948.
    https://pubmed.ncbi.nlm.nih.gov/22617948/

    Gerlach RF, Cury JA, Krug FJ, Line SR - "Effect of lead on dental enamel formation" Toxicology 175(1-3):27-34 (2002)
    doi: 10.1016/s0300-483x(02)00082-3. PMID: 12049833.

    see:

    Robinson C - "Enamel maturation: a brief background with implications for some enamel dysplasias" Front Physiol 5:388 (2014) doi: 10.3389/fphys.2014.00388. PMID: 25339913; PMCID: PMC4189374
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189374/

Tadpoles (Metamorphosis is under firm TH control)

Chai L, Li Y, Chen Z, Chen A, Deng H - "Responses of growth, malformation, and thyroid hormone-dependent genes expression in Bufo gargarizans embryos following chronic exposure to Pb2" Environ Sci Pollut Res Int 24(36):27953-27962 (2017)
doi: 10.1007/s11356-017-0413-4
https://pubmed.ncbi.nlm.nih.gov/28988273/
NOTE: Paradoxical [biphasic] effects on D3, as has been documented with fluoride.
"Slightly increased growth and development of B. gargarizans embryos were observed at low concentrations of Pb2+ (10, 50, and 100 μg L−1), while retarded growth and development were found at high concentrations of Pb2+ (1000 and 2000 μg L−1)."


Yang H, Liu R, Liang Z, Zheng R, Yang Y, Chai L, Wang H - "Chronic effects of lead on metamorphosis, development of thyroid gland, and skeletal ossification in Bufo gargarizans" Chemosphere 236:124251 (2019) doi: 10.1016/j.chemosphere.2019.06.221. Epub 2019 Jun 29. PMID: 31310984.
https://pubmed.ncbi.nlm.nih.gov/31310984/

Zebrafish (Model for endocrine toxicity)

Miao W, Zhu B, Xiao X, Li Y, Dirbaba NB, Zhou B, Wu H - " Effects of titanium dioxide nanoparticles on lead bioconcentration and toxicity on thyroid endocrine system and neuronal development in zebrafish larvae" Aquat Toxicol 161:117-26 (2015)
https://pubmed.ncbi.nlm.nih.gov/25703175/
("Zebrafish exposure to Pb alone at 30μg/L significantly decreased the thyroid hormone levels (T4 and T3)...")

Zhu B, Wang Q, Wang X, Zhou B - "Impact of co-exposure with lead and decabromodiphenyl ether (BDE-209) on thyroid function in zebrafish larvae" Aquat Toxicol. 157:186-95 (2014)
https://pubmed.ncbi.nlm.nih.gov/25456233/
(Pb exposure significantly decreased whole-body TH contents - T3 T4)
  • Sex-specific/Biphasic:

    Wang G, Wang T, Zhang X, Chen J, Feng C, Yun S, Cheng Y, Cheng F, Cao J - "Sex-specific effects of fluoride and lead exposures on histology, antioxidant physiology, and immune system in the liver of zebrafish (Danio rerio)" Ecotoxicology. 2022 Jan 27. doi: 10.1007/s10646-022-02519-5. Epub ahead of print. PMID: 35088223.
    https://pubmed.ncbi.nlm.nih.gov/35088223/
    "F + Pb treatment inhibited the growth performance traits of male zebrafish more than those of female zebrafish."

    "Moreover, F and Pb exposure of male zebrafish increased pro-inflammatory and anti-inflammatory cytokines expression, which was decreased after 90 days of exposure."
  • SEE also: Chen J, Xue W, Cao J, Song J, Jia R, Li M - "Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio)" Aquat Toxicol 171:48–58 (2016)
    https://doi.org/10.1016/jaquatox201512010

Lead & Gq/11
  • Activation of the Gq/11 family results in the stimulation of phospholipase C activity, leading to calcium mobilization and protein kinase C activation. Lead effects that result in learning and memory dysfunction are thought to be linked to calcium-triggered intracellular events (Fan et al., 2013; Liu et al., 1997). Gq/11 have been unequivocally established to be the transducing G proteins for Ca(2+)-mobilizing receptors (Exton, 1993).
Liu, JY, Lin, JK, Liu, CC, Chen, WK, Liu, CP, Wang, CJ - "Augumentation of protein kinase C activity and liver cell proliferation in lead nitrate-treated rats" Biochemistry and Molecular Biology International 43: 355–364 (1997)
"It is shown that lead alters calcium mediated cellular processes in several biological systems. Calcium enhances the activity of protein kinase C (PKC) which takes part in eliciting cell mitosis. ...This augmented activity of PKC was parallel with the increase of the lead level in the purified particulate fraction, although the protein levels of PKC alpha, PKC delta and PKC zeta were unchanged.....The results suggest that the PKC activation may be involved in promoting liver cell proliferation in lead nitrate-treated rats."

Fan G, Zhou F, Feng C, Wu F, Ye W, Wang C, Lin F, Yan J, Li Y, Chen Y, Bi Y - "Lead-induced ER calcium release and inhibitory effects of methionine choline in cultured rat hippocampal neurons" Toxicol In Vitro 27(1):387-95 (2013) doi: 10.1016/j.tiv.2012.06.019. Epub 2012 Aug 15. PMID: 22921426
https://pubmed.ncbi.nlm.nih.gov/22921426/
"Long term potentiation in the hippocampus, a potential neural substrate for learning and memory, is thought to be linked to calcium-triggered intracellular events. Long term potentiation in the hippocampus, a potential neural substrate for learning and memory, is thought to be linked to calcium-triggered intracellular events...The results showed that Pb(2+) increased [Ca(2+)](i) and decreased [Ca(2+)](ER) linearly in a time- and concentration-dependant manner...Our results suggest that Pb(2+) induces ER calcium release to increase the resting [Ca(2+)](i)."

Murakami K, Feng G, Chen SG - "Inhibition of brain protein kinase C subtypes by lead" J Pharmacol Exp Ther 264(2):757-61 (1993) PMID: 8437124.


Lead & D1 Deiodinase

Atteia HH, Arafa MH, Prabahar K - "Selenium nanoparticles prevents lead acetate-induced hypothyroidism and oxidative damage of thyroid tissues in male rats through modulation of selenoenzymes and suppression of miR-224" Biomed Pharmacother 99:486-491 (2018)
https://www.sciencedirect.com/science/a ... 2217350254
"This study, therefore, aimed to investigate and characterize the potential protective mechanism of Se-NPs against lead (Pb) acetate-induced thyrotoxicity. We found that prophylactic and concurrent treatment of Pb acetate-exposed rats with Nano-Se (0.5 mg/kg, i.p) for 15 wk significantly alleviated the decrease in free triiodothyronine (fT3) and free thyroxine (fT4) levels as well as fT3/fT4 ratio% and the increase in thyroid stimulating hormone (TSH) levels to approach control values. This was accompanied by a reduction in the accumulation of Pb in serum and thyroid tissues as well as maintenance of thyroidal pro-oxidant/antioxidant balance and iodothyronine deiodinase type 1 (ID1), an essential enzyme for metabolizing of T4 into active T3, gene expression. Surprisingly, miR-224, a direct complementary target of ID1 mRNA, expression in the thyroid tissues was significantly down-regulated in Nano-Se-pre- and co-treated Pb acetate intoxicated animals. Such changes in miR-224 expression were negatively correlated with the changes in ID1 gene expression and serum fT3 level. These results suggest that Se-NPs can rescue from Pb-induced impairment of thyroid function through the maintenance of selenoproteins and down-regulation of miR-224."

Chaurasia SS, Kar A - "Influence of lead on type-I iodothyronine 5'-monodeiodinase activity in male mouse" Horm Metab Res 29(10):532-3 (1997)
doi: 10.1055/s-2007-979096. PMID: 9405984
https://pubmed.ncbi.nlm.nih.gov/9405984/

Chaurasia SS, Gupta P, Maiti PK and Kar A - "Possible involvement of lipid peroxidation in the inhibition of type I iodothyronine 5'-monodeiodinase activity by lead in chicken liver" Journal of Applied Toxicology 18: 299-300 (1998)

Chaurasia SS, Panda S, Kar A - "Lead inhibits type-I iodothyronine 5'-monodeiodinase in Indian rock pigeon, Columba livia: A possible involvement of essential thiol groups" Journal of Biosciences 22:247-254 (1997)

Chaurasia SS, Kar A - "Lead induced oxidative damage to the membrane associated type I iodothyronine 5'-monodeiodinase activity in chicken liver homogenate" Fresenius Environmental Bulletin 7: 209-215 (1998)

Chaurasia SS, Kar A - "An oxidative mechanism for the inhibition of Iodothyronine 5'-monodeiodinase activity by lead nitrate in the fish, Heteropneustes fossilis" Water, Air and Soil Pollution 111:417-423 (1999)

Chaurasia SS, Gupta P, Kar A, Maiti PK - "Free radical mediated membrane perturbation and inhibition of type I iodothyronine5'-monodeiodinase activity by lead and cadmium in rat liver homogenate" IUBMB Life (Biochemistry and Molecular Biology International) 39 (4):765-770 (1997)

Chaurasia SS, Gupta P, Kar A, Maiti PK - "Lead induced thyroid dysfunction and lipid peroxidation in fish, Clarias batrachus with special reference to hepatic type I 5'-monodeiodinase activity" Bulletin of Environmental Contamination and Toxicology 56:649-654 (1996)

Chaurasia SS, Gupta P, Kar A, Maiti PK - "Lead impairs type-I 5'-monodeiodinase activity and thyroid function in cockerels" Current Science 69:698-700 (1995)

Chaurasia SS, Kar A - "Protective effects of vitamin E against lead-induced deterioration of membrane associated type-I iodothyronine 5'-monodeiodinase (5'D-I) activity in male mice" Toxicology 124(3):203-9 (1997)
"Daily intraperitoneal (i.p.) injection of lead acetate (0.5 mg/kg body weight) for 30 days significantly decreased serum 3,3',5-triiodothyronine (T3) concentration and hepatic 5'D-I activity."


Lead & D2, D3 Deiodinases

Chai L, Li Y, Chen Z, Chen A, Deng H - "Responses of growth, malformation, and thyroid hormone-dependent genes expression in Bufo gargarizans embryos following chronic exposure to Pb2" Environ Sci Pollut Res Int 24(36):27953-27962 (2017)
doi: 10.1007/s11356-017-0413-4
https://pubmed.ncbi.nlm.nih.gov/28988273/

Yang H, Liu R, Liang Z, Zheng R, Yang Y, Chai L, Wang H - "Chronic effects of lead on metamorphosis, development of thyroid gland, and skeletal ossification in Bufo gargarizans" Chemosphere 236:124251 (2019) doi: 10.1016/j.chemosphere.2019.06.221. Epub 2019 Jun 29. PMID: 31310984.
https://pubmed.ncbi.nlm.nih.gov/31310984/[/list]
  • See: Selenium:

    Liu MC, Xu Y, Chen YM, Li J, Zhao F, Zheng G, Jing JF, Ke T, Chen JY, Luo WJ - "The effect of sodium selenite on lead induced cognitive dysfunction" Neurotoxicology 36:82-8 (2013)
    https://pubmed.ncbi.nlm.nih.gov/23529067/

Lead & Fluoride

Denham M, Schell LM, Deane G, Gallo MV, Ravenscroft J, DeCaprio AP; Akwesasne Task Force on the Environment - "Relationship of lead, mercury, mirex, dichloro diphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls" Pediatrics 115(2):e127-34 (2005) doi: 10.1542/peds.2004-1161. Epub 2005 Jan 14. PMID: 15653789.
https://pubmed.ncbi.nlm.nih.gov/15653789/
  • Akwesasne is fluoride-polluted - see reports in database.
    SEE also: viewtopic.php?f=9&t=530; See also: Dundar lead study done in Isparta
Gutowska I, Baranowska-Bosiacka I, Siwiec E, Szczuko M, Kolasa A, Kondarewicz A, Rybicka M, Dunaj-Stańczyk M, Wiernicki I, Chlubek D, Stachowska E - "Lead enhances fluoride influence on apoptotic processes in the HepG2 liver cell line" Toxicol Ind Health 32(3):517-25 (2016)
doi: 10.1177/0748233713502843. Epub 2013 Nov 5. PMID: 24193047.
https://pubmed.ncbi.nlm.nih.gov/24193047/

Katsnelson BA, Privalova LI, Kireyeva YP, Yeremenko OS, Sutunkova MP, Valamina IE, Varaksin AN, Panov VG, Kazmer JI - "Combined subchronic fluoride-lead intoxication and its attenuation with the help of a complex of bioprotectors" Med Lav 103(2):146-59 (2012)
https://www.researchgate.net/publicatio ... protectors

Leite GA, Sawan RM, Teófilo JM, Porto IM, Sousa FB, Gerlach RF - "Exposure to lead exacerbates dental fluorosis" Arch Oral Biol 56(7):695-702 (2011)
https://pubmed.ncbi.nlm.nih.gov/21269604/
(Exposure to lead exacerbates dental fluorosis)

Maas RP, Patch SC, Christian AM, Coplan MJ - "Effects of fluoridation and disinfection agent combinations on lead leaching from leaded-brass parts" Neurotoxicology 28(5):1023-31 (2007)

Niu R, Sun Z, Cheng Z, Li Z, Wang J - "Decreased learning ability and low hippocampus glutamate in offspring rats exposed to fluoride and lead" Environ Toxicol Pharmacol 28(2):254-8 (2009)
https://pubmed.ncbi.nlm.nih.gov/21784012/

Panov VG, Katsnelson BA, Varaksin AN, Privalova LI, Kireyeva EP, Sutunkova MP, Valamina IE, Beresneva OY - "Further development of mathematical description for combined toxicity: A case study of lead-fluoride combination" Toxicol Rep 2:297-307 (2015)
https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC5598235/

Sawan RM, Leite GA, Saraiva MC, Barbosa F Jr, Tanus-Santos JE, Gerlach RF - "Fluoride increases lead concentrations in whole blood and in calcified tissues from lead-exposed rats" Toxicology 271(1-2):21-6 (2010) doi: 10.1016/j.tox.2010.02.002. Epub 2010 Feb 25. PMID: 20188782.
https://pubmed.ncbi.nlm.nih.gov/20188782/
Fluoride increases lead concentrations in whole blood and in calcified tissues from lead-exposed rats.

Tkachenko H, Kurhaluk N, Skaletska N, Maksin V, Osadowski Z - "Elemental Status and Lipid Peroxidation in the Blood of Children with Endemic Fluorosis" Biol Trace Elem Res (2020) doi: 10.1007/s12011-020-02243-3. Epub ahead of print. PMID: 32557098
https://pubmed.ncbi.nlm.nih.gov/32557098/
"In turn, a 1.7- and 1.4-fold increase in the strontium and lead content, respectively, was noted."

Wilsmann Krützmann M, Belem Machado A, da Silva Constante M, Aparecida Rigo K, Susana Perassolo M, Montanari Migliavacca Osório D, Bolzan Berlese D - "Evaluation of the effects of fluoride and associated with lead in animal model and physical-chemical analysis of public water supply and of the Sinos river in the South of Brazil" Int J for Innovation and Research 8(4):295-322 (2020) https://doi.org/10.31686/ijier.vol8.iss4.2290
"The results with the animals showed a significant difference in T3 (p=0.032) and in T4 (p=0.043) from G3 to G1. In TAC, the difference was significant from G2 to G1 and G3 (p=0.007), showing that F and F with Pb interfere with the endocrine and antioxidant functions of rats."

Xu Y, Huang H, Zeng Q, Yu C, Yao M, Hong F, Luo P, Pan X, Zhang A - "The effect of elemental content on the risk of dental fluorosis and the exposure of the environment and population to fluoride produced by coal-burning" Environ Toxicol Pharmacol 56:329-339 (2017)
doi: 10.1016/j.etap.2017.10.011. Epub 2017 Nov 6. PMID: 29101881
https://pubmed.ncbi.nlm.nih.gov/29101881/
"Subsequent univariate and multivariate regression analyses show that high levels of F, Al, As, Pb and Cr were a risk factor for dental fluorosis, but not Se, Zn, Cu, B, Ca and P which were a protective factor for dental fluorosis."


Sex-specific:

Wang G, Wang T, Zhang X, Chen J, Feng C, Yun S, Cheng Y, Cheng F, Cao J - "Sex-specific effects of fluoride and lead exposures on histology, antioxidant physiology, and immune system in the liver of zebrafish (Danio rerio)" Ecotoxicology. 2022 Jan 27. doi: 10.1007/s10646-022-02519-5. Epub ahead of print. PMID: 35088223.
https://pubmed.ncbi.nlm.nih.gov/35088223/
"F + Pb treatment inhibited the growth performance traits of male zebrafish more than those of female zebrafish."


Lead & Iodine

Xie Y, Zhou G - "Effects of meso-2,3-dimercaptosuccinic acid, potassium iodide and chlorophyll on lead accumulation in male mice" Int J Occup Med Environ Health 30(1):87-93 (21017) doi: 10.13075/ijomeh.1896.00406. Epub 2017 Feb 6. PMID: 28220909.
https://pubmed.ncbi.nlm.nih.gov/28220909/

Qiao YF, Pang DZ, Lu JF, Hu BY, Liu D, Zhou GF, Yang B, Li RS, Jiang YS - "Effect of potassium iodide on prevention of experimental lead nephropathy and expression of nuclear factor-kappaB and fibronectin" Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 27(12):747-52 (2009) Chinese. PMID: 21141136.
https://pubmed.ncbi.nlm.nih.gov/21141136/

Alatise OI, Schrauzer GN - "Lead exposure: a contributing cause of the current breast cancer epidemic in Nigerian women" Biol Trace Elem Res 136(2):127-39 (2010)
https://pubmed.ncbi.nlm.nih.gov/20195925/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883097/


Lead - Biphasic Effects

Chai L, Li Y, Chen Z, Chen A, Deng H - "Responses of growth, malformation, and thyroid hormone-dependent genes expression in Bufo gargarizans embryos following chronic exposure to Pb2" Environ Sci Pollut Res Int 24(36):27953-27962 (2017)
doi: 10.1007/s11356-017-0413-4
https://pubmed.ncbi.nlm.nih.gov/28988273/
[Slightly increased growth and development of B. gargarizans embryos were observed at low concentrations of Pb2+ (10, 50, and 100 μg L-1), while retarded growth and development were found at high concentrations of Pb2+ (1000 and 2000 μg L-1).]

Gilbert ME, Mack CM, Lasley SM - "Chronic developmental lead exposure and hippocampal long-term potentiation: biphasic dose-response relationship" Neurotoxicology 20(1):71-82 (1999)
https://pubmed.ncbi.nlm.nih.gov/10091860/
  • Gilbert showed the effects of hypothyroidism on synaptic function in the dentate gyrus [biphasic]:

    Gilbert ME, Sui L - "Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency" Brain Res 1069(1):10-22 (2006)
    https://pubmed.ncbi.nlm.nih.gov/16406011/

G Protein Investigations

Gillis BS, Arbieva Z, Gavin IM - "Analysis of lead toxicity in human cells" BMC Genomics 13:344 (2012)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424832/

Gorkhali R, Huang K, Kirberger M, Yang JJ - "Defining potential roles of Pb(2+) in neurotoxicity from a calciomics approach" Metallomics 8(6):563-78 (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979543/

Other References

Exton JH - "Role of G proteins in activation of phosphoinositide phospholipase C" Adv Second Messenger Phosphoprotein Res 28:65-72 (1993)
https://pubmed.ncbi.nlm.nih.gov/8398419/
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Lead & Adenylate Cyclase - Biphasic activity and other considerations

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Ewers U, Erbe R - "Effects of lead, cadmium and mercury on brain adenylate cyclase" Toxicology 16(3):227-37 (1980)
https://pubmed.ncbi.nlm.nih.gov/7423532/

Abstract

The effects of lead, cadmium and mercury ions on adenylate cyclase activity of rat cerebrum, cerebellum and brain stem were studied in vitro and in vivo. Adenylate cyclase activity in homogenates of cerebellum as well as cerebrum and brain stem was found to be inhibited by micromolar concentrations of these heavy metal ions in vitro. Administration of lead acetate trihydrate (25 mg/kg body wt i.v.) produced an initial increase of adenylate cyclase activity in the cerebellum and brain stem 1 h after injection, followed by a significant decrease of enzyme activity in cerebrum and cerebellum 4 h after the injection. Chronic lead treatment achieved by feeding lead containing diets, which generated blood lead levels of 31.3 +/- 3.8, 68.8 +/- 1.5 and 121.5 +/- 8.6 microgram Pb/100 g blood resp., produced a significant increase of brain lead levels and a 10-30% reduction of adenylate cyclase activity in cerebrum, cerebellum and brain stem. Phosphodiesterase activity was reduced under these conditions in the range of 10-20% in cerebellum and brain stem, but not in cerebrum.

Gq/11

Li ZG, Zhou FK, Yin AM, Gao YY, Jiang X, Liu SS, Zhang YY, Bo DD, Xie J, Jia QY, Feng JG, Feng C, Fan GQ - "Cellular damage of low-dose combined exposure to mercury, lead and cadmium on hippocampal neurons in rats" Zhonghua Yu Fang Yi Xue Za Zhi 52(10):976-982 (2018)
https://pubmed.ncbi.nlm.nih.gov/30392313/
"Conclusion: Low-level combined exposure to Hg, Pb, and Cd caused synergistic neurotoxic damage, and the process may be related to the changes of neuronal apoptosis, reactive oxide species, and [Ca(2+)](i) levels."

cAMP

Boyer IJ, DiStefano V - "An investigation of the mechanism of lead-induced relaxation of pigeon crop smooth muscle" J Pharmacol Exp Ther 234(3):616-23 (1985)
https://pubmed.ncbi.nlm.nih.gov/2863369/
https://jpet.aspetjournals.org/content/234/3/616.long

Nakade UP, Sharma A, Choudhury S, Yadav RS, Garg SK - "Lead Modulates Calcium Entry and Beta-Adrenoceptors Signaling to Produce Myometrial Relaxation in Rats" Biol Trace Elem Res 176(1):176-180 (2017)
https://pubmed.ncbi.nlm.nih.gov/27502953/

Tsao DA, Yu HS, Cheng JT, Ho CK, Chang HR - "Alterations in beta-adrenergic receptor density and adenylate cyclase activity in the rat brain treated chronically with lead" Toxicology 146(2-3):93-9 (2000)
https://pubmed.ncbi.nlm.nih.gov/10814842/
Brain AC was stimulated by lead...."In the study of Rossouw et al. (1987), lead exposure of neonatal rats resulted in significant increases of the apparent densities of forebrain cortical b-adrenoceptors (by 116%). This report suggested that low-level lead exposure at certain critical phases of development affects receptor ontogeny in developmental brain of neonatal rat. However, our results showed a significant decrease of b-adrenoceptors in mature rats. Thus, the effects of lead exposure for b-adrenoceptors in developing brain and mature brain may be vastly different."

Døskeland SO - "Guanine nucleotides protect adenylate cyclase against inhibition by Pb2+" Biochim Biophys Acta 630(1):15-21 (1980)
https://pubmed.ncbi.nlm.nih.gov/7388044/
"Guanine nucleotides strongly counteracted the reversible inhibition of cyclase by Pb2+, providing another example of guanine nucleotide effects on adenylate cyclase function. It is suggested that the Pb2+-inhibited cyclase may be of value in the study of guanine nucleotide-cyclase interactions."

Cutler LS - "Letter: Comments on the validity of the use of lead nitrate for the cytochemical study of adenylate cyclase" J Histochem Cytochem 23(10):786-7 (1975)
https://pubmed.ncbi.nlm.nih.gov/1194668/
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