SavedAdd your journal

Journals / Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Volume: 44 Issue: 1

Effects of Mercury Exposure on Neurodegenerative Diseases: Traditional Review

Cıva Maruziyetinin Nörodejeneratif Hastalıklar Üzerindeki Etkisi: Geleneksel Derleme

Elif Duru(TOBB EKONOMİ VE TEKNOLOJİ ÜNİVERSİTESİ)0000-0003-0934-9762
Hülya Tezel(HACETTEPE UNIVERSITY)0000-0002-1843-3424
Deniz Arca Çakır(HACETTEPE UNIVERSITY)0000-0002-6110-1775
Terken Baydar(HACETTEPE UNIVERSITY)0000-0002-5497-9600
Pınar Erkekoğlu(HACETTEPE ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, ECZACILIK MESLEK BİLİMLERİ BÖLÜMÜ, FARMASOTİK TOKSİKOLOJİ ANABİLİM DALI)0000-0003-4713-7672
Pages
—
Publication Date
2024-03-01
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In summary, it can be stated that mercury may be associated with neurodegeneration and related pathological conditions.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Due to environmental pollution, humans are exposed to various heavy metals, including mercury, in their daily lives.
📊
Key Findings & Data:Exposure to mercury causes degradation of proteins, increase in reactive oxygen species and enzyme inhibition.
💡
Conclusion & Impact:In summary, it can be stated that mercury may be associated with neurodegeneration and related pathological conditions.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Mercury · Alzheimer’s disease · Neurodegenerative diseases

Abstract

Due to environmental pollution, humans are exposed to various heavy metals, including mercury, in their daily lives. Mercury is common in nature and is used in thermometers, barometers, dental fillings. It is a toxic heavy metal and it exists in three different forms which has toxic effects through different mechanisms. Exposure to mercury causes degradation of proteins, increase in reactive oxygen species and enzyme inhibition. Neurodegenerative disorders are suggested to occur due to defective protein degradation and aggregation, mitochondrial dysfunction related to oxidative stress and free radical formation, and metal toxicity. There are various evidences that mercury and compounds cause neurodegenerative diseases. Because of mercury exposure, toxic effects such as DNA fragmentation and deterioration of the integrity of neurons can be observed. Severe damage to neurons results in neuronal loss, while neuronal loss makes it inevitable to observe neurodegenerative diseases. In this review, we summarized the studies about Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis, which are the main neurodegenerative diseases linked to mercury exposure. Studies showed that mercury exposure may be associated with all neurodegenerative diseases, especially Alzheimer’s disease. In summary, it can be stated that mercury may be associated with neurodegeneration and related pathological conditions.

Özet

Çevre kirliliği nedeniyle insanlar günlük yaşamlarında cıva da dahil olmak üzere çeşitli ağır metallere maruz kalmaktadır. Cıva doğada yaygın olarak bulunur ve termometrelerde, barometrelerde, diş dolgularında kullanılır. Toksik bir ağır metaldir ve farklı mekanizmalarla toksik etkileri olan üç farklı formda bulunur. Cıvaya maruz kalınması proteinlerin yapısında bozulma, reaktif oksijen türlerinde artma ve enzim inhibisyonu gibi çeşitli toksik etkilere yol açar. Nörodejeneratif bozuklukların, kusurlu protein yıkımı ve agregasyonu, oksidatif stres ve serbest radikal oluşumu ile ilgili mitokondriyal işlev bozukluğu ve metal toksisitesi nedeniyle ortaya çıktığı ileri sürülmektedir. Cıva ve bileşiklerinin nörodejeneratif hastalıklara neden olduğuna dair çeşitli kanıtlar vardır. Cıva maruziyeti nedeniyle DNA parçalanması ve nöronların bütünlüğünün bozulması gibi toksik etkiler gözlenebilir. Nöronların ciddi şekilde hasar görmesi nöronal kayıplara neden olurken, nöronal kayıplar nörodejeneratif hastalıkların görülmesini kaçınılmaz kılmaktadır. Bu derlemede, başlıca nörodejeneratif hastalıklardan Alzheimer hastalığı, Parkinson hastalığı, amyotrofik lateral skleroz ve multipl skleroz hastalıklarının cıva maruziyeti ile ilişkili olup olmadığı konusunda yapılan araştırmalar özetlenmiştir. Çalışmalar, cıva maruziyetinin başta Alzheimer hastalığı olmak üzere tüm nörodejeneratif hastalıklarla ilişkili olabileceğini göstermiştir. Özetle, cıvanın nörodejenerasyon ve buna bağlı patolojik durumlar ile ilişkili olabileceği ifade edilebilir.

🔖

Cite This Article

Duru, E., Tezel, H., Çakır, D. A., Baydar, T., Erkekoğlu, P. (2024). Effects of Mercury Exposure on Neurodegenerative Diseases: Traditional Review. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, Volume: 44 Issue: 1. https://doi.org/10.52794/hujpharm.1353188

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (69)

  1. PubChem. PubChem Element Summary for AtomicNumber 80, Mercury [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004. [cited October 2023]. Available from: https://pubchem.ncbi.nlm.nih.gov/element/Mercury
  2. USEPA. How People are Exposed to Mercury [Internet]. The United States Environmental Protection Agency; 2023. [cited October 2023]. Available from: https://www.epa.gov/mercury/how-people-are-exposed-mercury.
  3. Naija A, Yalcin HC. Evaluation of cadmium and mercury on cardiovascular and neurological systems: Effects on humans and fish. Toxicol Rep. 2023;10:498-508. https://doi.org/10.1016/j.toxrep.2023.04.009
  4. Sharma BM, Sáňka O, Kalina J, Scheringer M. An overview of worldwide and regional time trends in total mercury levels in human blood and breast milk from 1966 to 2015 and their associations with health effects. Environment international. 2019;125:300-19. https://doi.org/10.1016/j.envint.2018.12.016
  5. Tchounwou PB, Ayensu WK, Ninashvili N, Sutton D. Environmental exposure to mercury and its toxicopathologic implications for public health. Environ Toxicol. 2003;18(3):149-75. https://doi.org/10.1002/tox.10116
  6. Yiğit V, Müftügil N. Bazı balık türlerinde saptanan civa miktarları. Gıda. 1985;10(1):53-56.
  7. Yavuz CI. Environmental mercury exposure and health effects. Turkish Journal of Public Health. 2020;18(2):204-17. https://doi.org/10.20518/tjph.554605
  8. Fernandes Azevedo B, Barros Furieri L, Pecanha FM, Wiggers GA, Frizera Vassallo P, Ronacher Simoes M, et al. Toxic effects of mercury on the cardiovascular and central nervous systems. J Biomed Biotechnol. 2012;2012:949048. https://doi.org/10.1155/2012/949048
  9. Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006;36(8):609-62. https://doi.org/10.1080/10408440600845619
  10. Özbolat G, Abdullah T. Ağır metal toksisitesinin insan sağlığına etkileri. Arşiv Kaynak Tarama Dergisi. 2016;25(4):502-21. https://doi.org/10.17827/aktd.253562
  11. Hacioğlu C, Kar F, Kanbak G. Chronic mercury exposure: oxidative stress and neurotoxicity. Biological Diversity and Conservation. 2017;10(3):58-64.
  12. Brookes N, Kristt DA. Inhibition of amino acid transport and protein synthesis by HgCl2 and methylmercury in astrocytes: selectivity and reversibility. J Neurochem. 1989;53(4):1228-37. https://doi.org/10.1111/j.1471 4159.1989.tb07419.x
  13. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury-current exposures and clinical manifestations. N Engl J Med. 2003;349(18):1731-7. https://doi.org/10.1056/NEJMra022471
  14. Clarkson TW, Vyas JB, Ballatori N. Mechanisms of mercury disposition in the body. Am J Ind Med. 2007;50(10):757-64. https://doi.org/10.1002/ajim.20476
  15. Halbach S, Vogt S, Kohler W, Felgenhauer N, Welzl G, Kremers L, et al. Blood and urine mercury levels in adult amalgam patients of a randomized controlled trial: interaction of Hg species in erythrocytes. Environ Res. 2008;107(1):69-78. https://doi.org/10.1016/j.envres.2007.07.005
  16. Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, et al. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol. 1997;19(6):417-28. https://doi.org/10.1016/s0892-0362(97)00097-4
  17. Park JD, Zheng W. Human exposure and health effects of inorganic and elemental mercury. J Prev Med Public Health. 2012;45(6):344-52. https://doi.org/10.3961/jpmph.2012.45.6.344
  18. Von Burg R. Inorganic mercury. J Appl Toxicol. 1995;15(6):483-93. https://doi.org/10.1002/jat.2550150610
  19. Houston MC. The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. Altern Ther Health Med. 2007;13(2):128-133. https://doi.org/10.1111/j.1751-7176.2011.00489.x
  20. Dürer TS. Amalgam Dolgular. Bilimsel Tamamlayıcı Tıp Regülasyon ve Nöral Terapi Dergisi. 2017; 11(3):26-31.
  21. Balali-Mood M, Naseri K, Tahergorabi Z, Khazdair MR, Sadeghi M. Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic. Front Pharmacol. 2021;12:643972. https://doi.org/10.3389/fphar.2021.643972
  22. Pyatha S, Kim H, Lee D, Kim K. Association between Heavy Metal Exposure and Parkinson’s Disease: A Review of the Mechanisms Related to Oxidative Stress. Antioxidants (Basel).2022;11(12):2467. https://doi.org/10.3390/antiox11122467
  23. Fujimura M, Usuki F. Cellular Conditions Responsible for Methylmercury-Mediated Neurotoxicity. Int J Mol Sci. 2022;23(13):7218. https://doi.org/10.3390/ijms23137218
  24. Li B, Xia M, Zorec R, Parpura V, Verkhratsky A. Astrocytes in heavy metal neurotoxicity and neurodegeneration. Brain Res. 2021;1752:147234. https://doi.org/10.1016/j.brainres. 2020.147234
  25. Takanezawa Y, Sakai K, Nakamura R, Ohshiro Y, Uraguchi S, Kiyono M. Inhibition of p38 Mitogen-Activated Protein Kinases Attenuates Methylmercury Toxicity in SH-SY5Y Neuroblastoma Cells. Biol Pharm Bull. 2023;46(9):1203-10. https://doi.org/10.1248/bpb.b23-00014
  26. Kim BM, Choi AL, Ha EH, Pedersen L, Nielsen F, Weihe P, et al. Corrigendum to ‘Effect of hemoglobin adjustment on the precision of mercury concentrations in maternal and cord blood’ [Environ. Res. 132 (2014) 407-412]. Environ Res. 2016;147:630. https://doi.org/10.1016/j.envres.2016.01.015
  27. Heng YY, Asad I, Coleman B, Menard L, Benki-Nugent S, Hussein Were F, et al. Heavy metals and neurodevelopment of children in low and middle-income countries: A systematic review. PLoS One. 2022;17(3):e0265536. https://doi. org/10.1371/journal.pone.0265536
  28. Singh AD, Khanna K, Kour J, Dhiman S, Bhardwaj T, Devi K, et al. Critical review on biogeochemical dynamics of mercury (Hg) and its abatement strategies. Chemosphere. 2023;319:137917. https://doi.org/10.1016/j.chemosphere.2023.137917
  29. Ponce RA, Kavanagh TJ, Mottet NK, Whittaker SG, Faustman EM. Effects of methyl mercury on the cell cycle of primary rat CNS cells in vitro. Toxicol Appl Pharmacol. 1994;127(1):83-90. https://doi.org/10.1006/taap.1994.1142
  30. Llop S, Engstrom K, Ballester F, Franforte E, Alhamdow A, Pisa F, et al. Polymorphisms in ABC transporter genes and concentrations of mercury in newborns--evidence from two Mediterranean birth cohorts. PLoS One. 2014;9(5):e97172. https://doi.org/10.1371/journal.pone.0097172
  31. Yang L, Zhang Y, Wang F, Luo Z, Guo S, Strahle U. Toxicity of mercury: Molecular evidence. Chemosphere. 2020;245:125586. https://doi.org/10.1016/j.chemosphere.2019.125586
  32. Gundacker C, Wittmann KJ, Kukuckova M, Komarnicki G, Hikkel I, Gencik M. Genetic background of lead and mercury metabolism in a group of medical students in Austria. Environ Res. 2009;109(6):786-96. https://doi.org/10.1016/j.envres.2009.05.003
  33. Woods JS, Heyer NJ, Russo JE, Martin MD, Farin FM. Genetic polymorphisms affecting susceptibility to mercury neurotoxicity in children: summary findings from the Casa Pia Children’s Amalgam clinical trial. Neurotoxicology. 2014;44:288-302. https://doi.org/10.1016/j.neuro.2014.07.010
  34. Ijomone OM, Ijomone OK, Iroegbu JD, Ifenatuoha CW, Olung NF, Aschner M. Epigenetic influence of environmentally neurotoxic metals. Neurotoxicology. 2020;81:51-65. https://doi.org/10.1016/j.neuro.2020.08.005
  35. Onishchenko N, Karpova N, Sabri F, Castren E, Ceccatelli S. Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J Neurochem. 2008;106(3):1378-87. https://doi.org/10.1111/j.1471-4159.2008.05484.x
  36. Bose R, Onishchenko N, Edoff K, Janson Lang AM, Ceccatelli S. Inherited effects of low-dose exposure to methylmercury in neural stem cells. Toxicol Sci. 2012;130(2):383-90. https://doi.org/10.1093/toxsci/kfs257
  37. Xu X, Li Y-F, Zhao J, Li Y, Lin J, Li B, et al. Nanomaterial-based approaches for the detection and speciation of mercury. Analyst. 2015;140(23):7841-53. https://doi.org/10.1039/c5an01519g
  38. Cheng Z, Wei J, Gu L, Zou L, Wang T, Chen L, et al. DNAzyme-based biosensors for mercury (II) detection: Rational construction, advances and perspectives. J Hazard Mater. 2022;431:128606. https://doi.org/10.1016/j.jhazmat.2022.128606
  39. Chen J, Chakravarty P, Davidson GR, Wren DG, Locke MA, Zhou Y, et al. Simultaneous determination of mercury and organic carbon in sediment and soils using a direct mercury analyzer based on thermal decomposition-atomic absorption spectrophotometry. Anal Chim Acta. 2015;871:9-17. https://doi.org/10.1016/j.aca.2015.03.011
  40. Giacomino A, Ruo Redda A, Caligiuri R, Inaudi P, Squadrone S, Abete MC, et al. Development of an easy portable procedure for on-site determination of mercury and methylmercury. Food Chem. 2021;342:128347. https://doi.org/10.1016/j.foodchem.2020.128347
  41. Windmöller CC, Silva NC, Morais Andrade PH, Mendes LA, Magalhães do Valle C. Use of a direct mercury analyzer® for mercury speciation in different matrices without sample preparation. Analytical Methods. 2017;9(14):2159-67. https://doi.org/10.1039/C6AY03041F
  42. Agrawal M, Biswas A. Molecular diagnostics of neurodegenerative disorders. Front Mol Biosci. 2015;2:54. https://doi.org/10.3389/fmolb.2015.00054
  43. Nabi M, Tabassum N. Role of Environmental Toxicants on Neurodegenerative Disorders. Front Toxicol. 2022;4:837579. https://doi.org/10.3389/ftox.2022.837579
  44. Bjorklund G, Antonyak H, Polishchuk A, Semenova Y, Lesiv M, Lysiuk R, Peana M. Effect of methylmercury on fetal neurobehavioral development: an overview of the possible mechanisms of toxicity and the neuroprotective effect of phytochemicals. Arch Toxicol. 2022;96(12):3175-99. https://doi.org/10.1007/s00204-022-03366-3
  45. Li LX, Chu JH, Chen XW, Gao PC, Wang ZY, Liu C, Fan RF. Selenium ameliorates mercuric chloride-induced brain damage through activating BDNF/TrKB/PI3K/AKT and inhibiting NF-kappaB signaling pathways. J Inorg Biochem. 2022;229:111716. https://doi.org/10.1016/j.jinorgbio.2022.111716
  46. Branco V, Carvalho L, Barboza C, Mendes E, Cavaco A, Carvalho C. Selenium and Redox Enzyme Activity in Pregnant Women Exposed to Methylmercury. Antioxidants (Basel). 2022;11(11):2291. https://doi.org/10.3390/antiox11112291
  47. El-Sewify IM, Radwan A, Elghazawy NH, Fritzsche W, Azzazy HME. Optical chemosensors for environmental monitoring of toxic metals related to Alzheimer’s disease. RSC Adv. 2022;12(50):32744-55. https://doi.org/10.1039/d2ra05384e
  48. Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology. 2004;62(11):1984-9. https://doi.org/10.1212/01.wnl.0000129697.01779.0a
  49. Elonheimo HM, Andersen HR, Katsonouri A, Tolonen H. Environmental Substances Associated with Alzheimer’s Disease-A Scoping Review. Int J Environ Res Public Health. 2021;18(22):11839.https://doi.org/10.3390/ijerph182211839
  50. Siblerud R, Mutter J, Moore E, Naumann J, Walach H. A Hypothesis and Evidence That Mercury May be an Etiological Factor in Alzheimer’s Disease. Int J Environ Res Public Health. 2019;16(24):5152. https://doi.org/10.3390/ijerph16245152
  51. Drasch G, Schupp I, Riedl G, Günther G. Einfluß von Amalgamfüllungen auf die. Quecksilberkonzentration in menschlichen Organen. Dtsch Zahnärztl Z 1992;47:490-6. https://doi.org/10.1007/978-3-642-79156-7_48
  52. Guzzi G, Grandi M, Cattaneo C, Calza S, Minoia C, Ronchi A, et al. Dental amalgam and mercury levels in autopsy tissues: food for thought. Am J Forensic Med Pathol. 2006;27(1):42-5. https://doi.org/10.1097/01.paf.0000201177.62921.c8
  53. Mutter J, Naumann J, Sadaghiani C, Schneider R, Walach H. Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator. Neuroendocrinology Letters. 2004;25(5):331-9.
  54. Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci U S A. 2006;103(15):5644-51. https://doi.org/10.1073/pnas.0600549103
  55. Çilingir O, Adapinar BDÖ, Aras BD, Gökalp EE, Özkan S, Arslan S, et al. Türk Popülasyonunda APOE Polimorfizmleri ve Alzheimer Hastalığı Arasındaki İlişki. Osmangazi Tıp Dergisi. 2020;42(2):222-30. https://doi.org/10.20515/otd.553900
  56. Olivieri G, Brack C, Muller-Spahn F, Stahelin HB, Herrmann M, Renard P, et al. Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells. J Neurochem. 2000;74(1):231-6. https://doi.org/10.1046/j.1471-4159.2000.0740231.x
  57. Fujimura M, Usuki F, Sawada M, Takashima A. Methylmercury induces neuropathological changes with tau hyperphosphorylation mainly through the activation of the c-jun-N-terminal kinase pathway in the cerebral cortex, but not in the hippocampus of the mouse brain. Neurotoxicology. 2009;30(6):1000-7. https://doi.org/10.1016/j.neuro.2009.08.001
  58. Hoffman HI, Bradley WG, Chen CY, Pioro EP, Stommel EW, Andrew AS. Amyotrophic Lateral Sclerosis Risk, Family Income, and Fish Consumption Estimates of Mercury and Omega- 3 PUFAs in the United States. Int J Environ Res Public Health. 2021;18(9):4528.https://doi.org/10.3390/ijerph18094528
  59. Cariccio VL, Sama A, Bramanti P, Mazzon E. Mercury Involvement in Neuronal Damage and in Neurodegenerative Diseases. Biol Trace Elem Res. 2019;187(2):341-56. https://doi.org/10.1007/s12011-018-1380-4
  60. Schwarz S, Husstedt I, Bertram HP, Kuchelmeister K. Amyotrophic lateral sclerosis after accidental injection of mercury. J Neurol Neurosurg Psychiatry. 1996;60(6):698. https://doi.org/10.1136/jnnp.60.6.698
  61. Johnson FO, Atchison WD. The role of environmental mercury, lead and pesticide exposure in development of amyotrophic lateral sclerosis. Neurotoxicology. 2009;30(5):761-5. https://doi.org/10.1016/j.neuro.2009.07.010
  62. Arvidson B. Inorganic mercury is transported from muscular nerve terminals to spinal and brainstem motoneurons. Muscle Nerve. 1992;15(10):1089-94. https://doi.org/10.1002/mus.880151006
  63. Rustam H, Von Burg R, Amin-Zaki L, El Hassani S. Evidence for a neuromuscular disorder in methylmercury poisoning. Arch Environ Health. 1975;30(4):190-5. https://doi.org/10.1080/00039896.1975.10666674
  64. Bakir F, Damluji SF, Amin-Zaki L, Murtadha M, Khalidi A, al-Rawi NY, et al. Methylmercury poisoning in Iraq. Science. 1973;181(4096):230-41. https://doi.org/10.1126/science.181.4096.230
  65. Mahaffey KR, Clickner RP, Bodurow CC. Blood organic mercury and dietary mercury intake: National Health and Nutrition Examination Survey, 1999 and 2000. Environ Health Perspect. 2004;112(5):562-70. https://doi.org/10.1289/ehp.6587
  66. Sarihi S, Niknam M, Mahjour S, Hosseini-Bensenjan M, Moazzen F, Soltanabadi S, Akbari H. Toxic heavy metal concentrations in multiple sclerosis patients: A systematic review and meta-analysis. EXCLI J. 2021;20:1571-84. https://doi.org/10.17179/excli2021-3484
  67. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502-17. https://doi.org/10.1016/S0140-6736(08)61620-7
  68. Visconti A, Cotichini R, Cannoni S, Bocca B, Forte G, Ghazaryan A, et al. Concentration of elements in serum of patients affected by multiple sclerosis with first demyelinating episode: a six-month longitudinal follow-up study. Ann Ist Super Sanita. 2005;41(2):217-22.
  69. Giacoppo S, Galuppo M, Calabrò RS, D’Aleo G, Marra A, Sessa E, et al. Heavy metals and neurodegenerative diseases: an observational study. Biological trace element research. 2014;161:151-60. https://doi.org/10.1007/s12011-014-0094-5