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Highlights of Heavy Metals: Molecular Toxicity Mechanisms, Exposure Dynamics, and Environmental Presence

1,2Esther Ugo Alum

1Department of Biochemistry, Faculty of Science, Ebonyi State University, P.M.B. 053 Abakaliki, Ebonyi State, Nigeria.

2Department of Publication and Extension Kampala International University Uganda

*Corresponding author: Esther Ugo Alum;

Email: esther.alum@ebsu.edu.ng; +2348034789993

ABSTRACT

Elements denser than water are known as heavy metals, and they are a major global danger to the environment and human health. The ubiquity of each metal in diverse environmental matrices is highlighted by its existence in both natural and industrial sources. Human exposure pathways include everything from food consumption to work environments, and they all contribute to a variety of health effects and organ system damage. Notably, long-term exposure to these metals is associated with increased cancer incidence rates, which can impact the neurological systems, lungs, kidneys, skin, liver, and other organs. The molecular details of the toxicity and carcinogenicity of individual metals reveal a variety of processes, such as DNA damage, oxidative stress induction, disruption of cellular respiration, disruption of signal transduction pathways, and changes in gene expression. Priority heavy metals (cadmium, chromium, arsenic, lead, and mercury) have distinct toxicological profiles, but this review emphasizes the urgent need for comprehensive strategies to reduce environmental contamination and human exposure. It does this by highlighting the complex interactions between environmental events, anthropological sources, and the molecular basis of heavy metal-induced carcinogenicity and toxicity.

Keywords: Environmental Contamination, Heavy Metals, Environmental Health Impacts, Molecular Mechanisms, Metal Toxicity

INTRODUCTION

Heavy metals are metallic elements denser than water. Metalloids that are hazardous at low exposure levels, such as arsenic, are also classified as heavy metals if toxicity and heaviness are associated [1]. These metals’ poisoning of the environment has become an increasingly serious worldwide ecological and public health issue in recent years. Furthermore, human exposure has significantly increased as a result of the exponential growth in the number of industrial, agricultural, household, and technical applications of these compounds [2]. Known sources of heavy metals in the environment include geogenic, industrial, agricultural, pharmaceutical, domestic effluent, and atmospheric [3]. Major sources of pollution to the environment are metal-based industrial operations and point sources such as foundries, smelters, and mines [2, 3]. The main ways that humans contaminate and come into contact with naturally existing elements like heavy metals are through mining, industrial production, and agricultural use. Air deposition, soil erosion, leaching, sediment re-suspension, metal evaporation, and metal corrosion are additional sources [3, 4]. It has also been noted that weathering and volcanic eruptions are examples of natural events that greatly contribute to heavy metal contamination [5]. Paper processing factories, plastics, textiles, microelectronics, wood preservation, metal processing in refineries, coal burning in power plants, petroleum combustion, nuclear power plants, and high tension lines are examples of industrial sources [5]. According to reports, metals including zinc (Zn), cobalt (Co), copper (Cu), chromium (Cr), iron (Fe), manganese (Mn), magnesium (Mg), molybdenum (Mo), nickel (Ni), selenium (Se), and zinc (Mg) are necessary nutrients needed for a variety of physiological and biochemical processes [6]. Numerous deficiency illnesses or syndromes are brought on by an inadequate intake of certain micronutrients [6]. Physical factors that affect heavy metals include temperature, phase association, adsorption, sequestration, complexation kinetics, lipid solubility, and chemical variables. Heavy metals are present in trace levels in a variety of environmental matrices [7, 8]. Additionally, biological elements such trophic relationships, species traits, and physiological and biochemical adaptability are crucial [9]. In both plants and animals, the important heavy metals perform physiological and metabolic roles. They are crucial components of a number of essential enzymes and are involved in a number of different oxidation-reduction processes [6]. Ferroxidases, catalase, and peroxidase are among the enzymes linked to oxidative stress for which copper is an essential co-factor. For the creation of hemoglobin, the metabolism of carbohydrates, the manufacture of catecholamines, and the cross-linking of collagen, it is integrated into metalloenzymes. Cuproenzymes make use of the reduced and oxidized forms of copper [10]. But because superoxide and hydroxyl radicals can be produced during the switches among Cu(II) and Cu(I), this feature of copper also gives it the potential to be poisonous [11]. Additionally, Wilson disease in humans has been related to cellular damage caused by high copper exposure [10, 11]. Like copper, a number of other elements are necessary for biologic functioning; however, an excess of these elements results in damage to cells and tissues, which can lead to a variety of negative effects and human diseases. For some, like copper and chromium, there is a very narrow range of concentrations between beneficial and toxic effects [11, 12]. Other elements, like aluminum (Al), antinomy (Sb), arsenic (As), barium (Ba), beryllium (Be), bismuth (Bi), cadmium (Cd), gallium (Ga), germanium (Ge), gold (Au), indium (In), lead (Pb), lithium (Li), nickel (Ni), platinum (Pt), silver (Ag), strontium (Sr), tellurium (Te), thallium (Tl), tin (Sn), titanium (Ti), vanadium (V), and uranium (U) have no known biological functions and are regarded as non-essential metals [12]. The effects of heavy metals on cellular organelles and components in biological systems have been documented. These consist of the endoplasmic reticulum, mitochondria, lysosome, cell membrane, nuclei, and specific enzymes that are involved in damage repair, metabolism, and detoxification [13]. Metal ions can cause damage and conformational changes to DNA and nuclear proteins, which can lead to apoptosis, cancer, or abnormalities in the cell cycle. Some laboratory research has shown in multiple studies that the generation of reactive oxygen species (ROS) and oxidative stress are important factors in the toxicity and carcinogenicity of metals including arsenic [14], cadmium [15], chromium [16], lead [17], and mercury [18]. These five elements are considered priority metals of major public health relevance due to their high degree of toxicity. Even at lower exposure levels, these are all recognized to be systemic toxicants that can cause damage to various organs. There are numerous mechanistic components to heavy metal-induced toxicity and carcinogenicity, some of which are not fully understood or clarified. Nonetheless, it is well recognized that every metal has distinct characteristics and physicochemical qualities that give rise to particular toxicological modes of action. The environmental occurrence, production and usage, human exposure potential, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity of arsenic, cadmium, chromium, lead, and mercury are all reviewed in this article using relevant published articles from various scholarly databases.

                                                           CONCLUSION

This paper explores the environmental impact of heavy metals such as cadmium, chromium, lead, mercury, and arsenic their toxicity and carcinogenicity. These metals are found in various sources, including food, work, and pollution. Long-term exposure can cause organ damage and cancer. The toxicity mechanisms include oxidative stress, signal transduction disruption, DNA damage, and gene expression changes. The paper calls for interdisciplinary research to understand these metals’ interactions and develop effective policies to minimize environmental contamination and mitigate health risks.

                                                            REFERENCES

  1. Duffus JH. Heavy metals-a meaningless term? Pure Appl Chem. 2002;74(5):793–807. 
  2. Bradl H, editor. Heavy Metals in the Environment: Origin, Interaction and Remediation Volume 6.London: Academic Press; 2002. 
  3. He ZL, Yang XE, Stoffella PJ. Trace elements in agroecosystems and impacts on the environment. J Trace Elem Med Biol. 2005;19(2–3):125–140.
  4. Nriagu JO. A global assessment of natural sources of atmospheric trace metals. 1989;338:47–49. 
  5. Arruti A, Fernández-Olmo I, Irabien A. Evaluation of the contribution of local sources to trace metals levels in urban PM2.5 and PM10 in the Cantabria region (Northern Spain) J Environ Monit. 2010;12(7):1451–1458.
  6. WHO/FAO/IAEA. World Health Organization. Switzerland: Geneva; 1996. Trace Elements in Human Nutrition and Health. [Google Scholar]
  7. Kabata- Pendia A 3rd, editor. Trace Elements in Soils and Plants.Boca Raton, FL: CRC Press; 2001. [Google Scholar]
  8. Hamelink JL, Landrum PF, Harold BL, William BH, editors. Bioavailability: Physical, Chemical, and Biological Interactions.Boca Raton, FL: CRC Press Inc; 1994. [Google Scholar]
  9. Verkleji JAS. In: The effects of heavy metals stress on higher plants and their use as biomonitors In Plant as Bioindicators: Indicators of Heavy Metals in the Terrestrial Environment.Markert B, editor. New York: VCH; 1993. pp. 415–424. [Google Scholar]
  10. Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profile for Copper. Atlanta, GA: Centers for Disease Control; 2002.
  11. Tchounwou P, Newsome C, Williams J, Glass K. Copper-induced cytotoxicity and transcriptional activation of stress genes in human liver carcinoma cells. Metal Ions Biol Med. 2008;10:285–290. [PMC free article][PubMed] [Google Scholar]
  12. Chang LW, Magos L, Suzuki T, editors. Toxicology of Metals. Boca Raton. FL, USA: CRC Press; 1996.
  13. Wang S, Shi X. Molecular mechanisms of metal toxicity and carcinogenesis. Mol Cell Biochem. 2001;222:3–9.
  14. Tchounwou PB, Centeno JA, Patlolla AK. Arsenic toxicity, mutagenesis and carcinogenesis – a health risk assessment and management approach. Mol Cell Biochem. 2004;255:47–55. 
  15. Tchounwou PB, Ishaque A, Schneider J. Cytotoxicity and transcriptional activation of stress genes in human liver carcinoma cells (HepG2) exposed to cadmium chloride. Mol Cell Biochem. 2001;222:21–28.
  16. Patlolla A, Barnes C, Field J, Hackett D, Tchounwou PB. Potassium dichromate-induced cytotoxicity, genotoxicity and oxidative stress in human liver carcinoma (HepG2) cells. Int J Environ Res Public Health. 2009;6:643–653.
  17. Tchounwou PB, Yedjou CG, Foxx D, Ishaque A, Shen E. Lead-induced cytotoxicity and transcriptional activation of stress genes in human liver carcinoma cells (HepG2) Mol Cell Biochem. 2004;255:161–170.
  18. Sutton D, Tchounwou PB, Ninashvili N, Shen E. Mercury induces cytotoxicity, and transcriptionally activates stress genes in human liver carcinoma cells. Intl J Mol Sci. 2002;3(9):965–984. 
  19. Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profile for Arsenic TP-92/09. Georgia: Center for Disease Control, Atlanta; 2000. 
  20. Tchounwou PB, Wilson B, Ishaque A. Important considerations in the development of public health advisories for arsenic and arsenic-containing compounds in drinking water. Rev Environ Health. 1999;14(4):211–229.
  21. Morton WE, Dunnette DA. Health effects of environmental arsenic. In: Nriagu JO, editor. Arsenic in the Environment Part II: Human Health and Ecosystem Effects.New York: John Wiley & Sons, Inc; 1994. pp. 17–34. 
  22. National Research Council. Arsenic in Drinking Water. 2001 Update. 2001 On line at: http://www.nap.edu/ books/0309076293/html/
  23. Hughes MF. Arsenic toxicity and potential mechanisms of action. Toxicol Lett. 2002;133:1–16.
  24. Basu A, Mahata J, Gupta S, Giri AK. Genetic toxicology of a paradoxical human carcinogen, arsenic: a review. Mutat Res. 2001;488:171–194.
  25. Saleha Banu B, Danadevi K, Kaiser Jamil, Ahuja YR, Visweswara Rao K, Ishap M. In vivogenotoxic effect of arsenic trioxide in mice using comet assay.  2001;162:171–177. 
  26. Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP. Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci USA. 1997;94:10907–10912.
  27. Ludwig S, Hoffmeyer A, Goebeler M, Kilian K, Hafner H, Neufeld B, Han J, Rapp UR. The stress inducer arsenite activates mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 via a MAPK kinase 6/p38- dependent pathway. J Biol Chem. 1998;273:1917–1922. 
  28. Trouba KJ, Wauson EM, Vorce RL. Sodium arsenite-induced dysregulation of proteins involved in proliferative signaling. Toxicol Appl Pharmacol. 2000;164(2):161–170. 
  29. Porter AC, Fanger GR, Vaillancourt RR. Signal tansduction pathways regulated by arsenate and arsenite. 1999;18(54):7794–7802.
  30. Murgo AJ. Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies. 2001;6(2):22–28. 
  31. Alemany M, Levin J. The effects of arsenic trioxide on human Megakaryocytic leukemia cell lines with a comparison of its effects on other cell lineages. Leukemia Lymphoma. 2000;38(1–2):153–163.
  32. Wilson DN Association Cadmium. Cadmium – market trends and influences; London. Cadmium 87 Proceedings of the 6th International Cadmium Conference; 1988. pp. 9–16.
  33. Paschal DC, Burt V, Caudill SP, Gunter EW, Pirkle JL, Sampson EJ, et al. Exposure of the U.S. population aged 6 years and older to cadmium: 1988–1994. Arch Environ Contam Toxicol. 2000;38:377–383. 
  34. Mascagni P, Consonni D, Bregante G, Chiappino G, Toffoletto F. Olfactory function in workers exposed to moderate airborne cadmium levels. 2003;24:717–724. 
  35. Elinder CG, Järup L. Cadmium exposure and health risks: Recent findings. 1996;25:370.
  36. Baselt RC, Cravey RH. Disposition of Toxic Drugs and Chemicals in Man.4th Edn. Chicago, IL: Year Book Medical Publishers; 1995. pp. 105–107.
  37. Baselt RC. Disposition of Toxic Drugs and Chemicals in Man.5th Ed. Foster City, CA: Chemical Toxicology Institute; 2000.
  38. Stohs Bagchi. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med. 1995;18:321–336.
  39. Landolph J. Molecular mechanisms of transformation of CH3/10T1/2 C1 8 mouse embryo cells and diploid human fibroblasts by carcinogenic metal compounds. Environ Health Perspect. 1994;102:119–125. 
  40. International Agency for Research on Cancer (IARC) Monographs – Cadmium.Lyon, France: 1993.
  41. Nishijo M, Tawara K, Honda R, Nakagawa H, Tanebe K, Saito S. Relationship between newborn size and mother’s blood cadmium levels, Toyama, Japan. Arch Environ Health. 2004;59(1):22–25. 
  42. S. EPA. Environmental Criteria and Assessment Office.Cincinnati, OH: United States Environmental Protection Agency; 1992. Integrated Risk Information System (IRIS) 
  43. Cohen MD, Kargacin B, Klein CB, Costa M. Mechanisms of chromium carcinogenicity and toxicity. Crit Rev Toxicol. 1993;23:255–281.
  44. Singh J, Pritchard DE, Carlisle DL, Mclean JA, Montaser A, Orenstein JM, Patierno SR. Internalization of carcinogenic lead chromate particles by cultured normal human lung epithelial cells: Formation of intracellular lead-inclusion bodies and induction of apoptosis. Toxicol Appl Pharmacol. 1999;161:240–248. 
  45. Goyer RA. Toxic effects of metals. In: Klaassen CD, editor. Cassarett and Doull’s Toxicology: The Basic Science of Poisons.New York: McGraw-Hill Publisher; 2001. pp. 811–867.
  46. De Flora S, Bagnasco M, Serra D, Zanacchi P. Genotoxicity of chromium compounds: a review. Mutat Res. 1990;238:99–172.
  47. Kim E, Na KJ. Nephrotoxicity of sodium dichromate depending on the route of administration. Arch Toxicol. 1991;65:537–541.
  48. Zhitkovich A, Song Y, Quievryn G, Voitkun V. Non-oxidative mechanisms are responsible for the induction of mutagenesis by reduction of Cr(VI) with cysteine: role of ternary DNA adducts in Cr(III)-dependent mutagenesis. 2001;40(2):549–60.
  49. Gabby PN. “Lead.” Environmental Defense “Alternatives to Lead-Acid Starter Batteries,” Pollution Prevention Fact Sheet. 2003 available at http://www.cleancarcampaign.org/FactSheet_BatteryAlts.pdf.
  50. Centers for Disease control (CDC) Preventing Lead Poisoning in Young children: A statement by the Centers for Disease Control.Atlanta, GA: 1991. [Google Scholar]
  51. Jacobs DE, Clickner RP, Zhou JY, et al. The prevalence of lead-based paint hazards in U.S. housing. Environ Health Perspect. 2002;110:A599–A606. [PMC free article][PubMed] [Google Scholar]
  52. Farfel MR, Chisolm JJ., Jr An evaluation of experimental practices for abatement of residential lead-based paint: report on a pilot project. Environ Res. 1991;55:199–212.
  53. Centers for Disease Control and Prevention CDC) Managing Elevated Blood Lead Levels Among Young Children: Recommendations From the Advisory Committee on Childhood Lead Poisoning Prevention.Atlanta: 2001. [Google Scholar]
  54. Lanphear BP, Matte TD, Rogers J, et al. The contribution of lead-contaminated house dust and residential soil to children’s blood lead levels. A pooled analysis of 12 epidemiologic studies. Environ Res. 1998;79:51–68. 
  55. Agency for Toxic Substances and Disease Registry (ATSDR. Public Health Service.Atlanta: U.S. Department of Health and Human Services; 1999. Toxicological Profile for Lead.
  56. Huel G, Tubert P, Frery N, Moreau T, Dreyfus J. Joint effect of gestational age and maternal lead exposure on psychomotor development of the child at six years. 1992;13:249–254.
  57. United States Environmental Protection Agency (U.S. EPA) Lead Compounds. Technology Transfer Network- Air Toxics Website. 2002 Online at: http://www.epa.gov/cgi-bin/epaprintonly.cgi.
  58. Jiun YS, Hsien LT. Lipid peroxidation in workers exposed to lead. Arch Environ Health. 1994;49:256–259. 
  59. Bechara EJ, Medeiros MH, Monteiro HP, Hermes-Lima M, Pereira B, Demasi M. A free radical hypothesis of lead poisoning and inborn porphyrias associated with 5-aminolevulinic acid overload. Quim Nova. 1993;16:385–392. 
  60. Yedjou CG, Steverson M, Paul Tchounwou PB. Lead nitrate-induced oxidative stress in human liver carcinoma (HepG2) cells. Metal Ions Biol Med. 2006;9:293–297. 
  61. Simons T. Lead-calcium interactions in cellular lead toxicity. 1993;14:77–86. 
  62. Vijverberg HPM, Oortgiesen M, Leinders T, van Kleef RGDM. Metal interactions with voltage- and receptor-activated ion channels. Environ Health Perspect. 1994;102(3):153–158.
  63. Goldstein G. Evidence that lead acts as a calcium substitute in second messenger metabolism. 1993;14:97–102.
  64. International Agency for Research on Cancer (IARC) In IARC Monographs on the Evaluation of Carcinogenic Risks to Humans.Supplement 7. Volumes 1–42. Lyons, France: IARC; 1987. Overall Evaluation of Carcinogenicity: An updating of Monographs; pp. 230–232.
  65. Waalkes MP, Hiwan BA, Ward JM, Devor DE, Goyer RA. Renal tubular tumors and a typical hepper plasics in B6C3F, mice exposed to lead acetate during gestation and lactation occur with minimal chronic nephropathy. Cancer Res. 1995;55:5265–5271.
  66. Yang JL, Wang LC, Chamg CY, Liu TY. Singlet oxygen is the major species participating in the induction of DNA strand breakage and 8-hydrocy-deoxyguanosine adduct by lead acetate. Environ Mol Mutagen. 1999;33:194–201.
  67. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury-current exposures and clinical manifestations. New Engl J Med. 2003;349:1731–1737. 
  68. Dopp E, Hartmann LM, Florea AM, Rettenmier AW, Hirner AV. Environmental distribution, analysis, and toxicity of organometal (loid) compounds. Crit Rev Toxicol. 2004;34:301–333. 
  69. Tchounwou PB, Ayensu WK, Ninashvilli N, Sutton D. Environmental exposures to mercury and its toxicopathologic implications for public health. Environ Toxicol. 2003;18:149–175.
  70. S. EPA (Environmental Protection Agency) Mercury Study Report to Congress. 1997 Available at: http://www.epa.gov/mercury/report.htm.
  71. Sarkar BA. Mercury in the environment: Effects on health and reproduction. Rev Environ Health. 2005;20:39–56.
  72. Sanfeliu C, Sebastia J, Cristofol R, Rodriquez-Farre E. Neurotoxicity of organomercurial compounds.  Res. 2003;5:283–305. 
  73. Valko M, Morris H, Cronin MTD. Metals, Toxicity, and oxidative Stress. Curr Medici Chem. 2005;12:1161–1208.
  74. Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006;36:609–662.
  75. Rooney JPK. The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury. 2007;234:145–156.
  76. Amorim MI, Mergler D, Bahia MO, Miranda H, Lebel J. Cytogenetic damage related to low levels of methylmercury contamination in the Brazilian Amazon. Ann Acad Bras Cienc. 2000;72:497–507.

CITE AS: Esther Ugo Alum (2023). Highlights of Heavy Metals: Molecular Toxicity Mechanisms, Exposure Dynamics, and Environmental Presence. IAA Journal of Applied Sciences 10(3):8-19. https://doi.org/10.59298/IAAJAS/2023/4.2.3222 

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