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Abstract

The majority of the heavy metals are considered toxic to the human beings by interfering with the normal functions that are taking place in the human body by disrupting metabolic processes and their exposure may be due to natural or anthropogenic sources. Heavy metals act as endocrine-disrupting chemicals (EDCs) by disrupting the mechanism of action of endogenous substances. Heavy metals such as cadmium and arsenic have a negative impact on some enzymes that are involved in carbohydrates and lipids metabolism and lead to an abnormal level of glucose and lipid, cholesterol, and triglycerides. This is responsible for inducing the pathogenesis associated with diabetes mellitus and insulin resistance. These metals are also responsible to induce reactive oxygen species and suppress antioxidant defense mechanism. The stress-induced by oxidation is highly linked with metabolic syndrome. These conditions lead to a risk of diabetes-associated cardiovascular diseases. While on the other side, some of the heavy metals notably zinc which is considered as an essential nutrient, play its significant role in metabolic disorders by suppressing oxidant effect, reducing obesity and lipogenesis. In this chapter, we have briefly overviewed the role of heavy metals that act as EDCs in metabolic disorder via interfering various transcriptional and metabolic pathways while the other heavy metals which have a beneficial role in the amelioration of metabolic disorders.

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References

  1. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al. EDC-2: The Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev. 2015;36(6):E1–E150.

    CAS  Google Scholar 

  2. Georgescu B, Georgescu C, Dărăban S, Bouaru A, Paşcalău S. Heavy metals acting as endocrine disrupters. Sci Pap Anim Sci Biotechnol. 2011;44(2):89–93.

    Google Scholar 

  3. Yadav M, Gupta R, Sharma RK. Chapter 14 - green and sustainable pathways for wastewater purification. In: Ahuja S, editor. Advanced water purification techniques. Amsterdam: Elsevier; 2019. p. 355–83.

    Google Scholar 

  4. Verma N, Kaur G. Chapter 2 - trends on biosensing systems for heavy metal detection. In: Scognamiglio V, Rea G, Arduini F, Palleschi G, editors. Comprehensive analytical chemistry, vol. 74. Amsterdam: Elsevier; 2016. p. 33–71.

    Google Scholar 

  5. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. Experientia Suppl. 2012;101:133–64.

    Google Scholar 

  6. Engwa GA, Ferdinand PU, Nwalo FN, Unachukwu MN. Mechanism and health effects of heavy metal toxicity in humans. In: Karcioglu O, Arslan B, editors. Poisoning in the modern world-new tricks for an old dog? London: Intechopen; 2019.

    Google Scholar 

  7. Jarup L, Berglund M, Elinder CG, Nordberg G, Vahter M. Health effects of cadmium exposure--a review of the literature and a risk estimate. Scand J Work Environ Health. 1998;24(Suppl 1):1–51.

    Google Scholar 

  8. Huang Y, He C, Shen C, Guo J, Mubeen S, Yuan J, et al. Toxicity of cadmium and its health risks from leafy vegetable consumption. Food Funct. 2017;8(4):1373–401.

    CAS  Google Scholar 

  9. Schwartz GG, Reis IM. Is cadmium a cause of human pancreatic cancer? Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research. Am Soc Prev Oncol. 2000;9(2):139–45.

    CAS  Google Scholar 

  10. Kumari A. Chapter 1 - glycolysis. In: Kumari A, editor. Sweet biochemistry. Cambridge: Academic Press; 2018. p. 1–5.

    Google Scholar 

  11. Veramendi J, Fernie AR, Leisse A, Willmitzer L, Trethewey RN. Potato hexokinase 2 complements transgenic Arabidopsis plants deficient in hexokinase 1 but does not play a key role in tuber carbohydrate metabolism. Plant Mol Biol. 2002;49(5):491–501.

    CAS  Google Scholar 

  12. Sabir S, Akash MSH, Fiayyaz F, Saleem U, Mehmood MH, Rehman K. Role of cadmium and arsenic as endocrine disruptors in the metabolism of carbohydrates: inserting the association into perspectives. Biomed Pharmacother. 2019;114:108802.

    CAS  Google Scholar 

  13. Sastry KV, Subhadra K. Effect of cadmium on some aspects of carbohydrate metabolism in a freshwater catfish Heteropneustes fossilis. Toxicol Lett. 1982;14(1):45–55.

    CAS  Google Scholar 

  14. Cicik B, Engin K. The effects of cadmium on levels of glucose in serum and glycogen reserves in the liver and muscle tissues of Cyprinus carpio (L., 1758). Turk J Vet Animal Sci. 2005;29:113–7.

    CAS  Google Scholar 

  15. De la Torre FR, Salibian A, Ferrari L. Biomarkers assessment in juvenile Cyprinus carpio exposed to waterborne cadmium. Environ Pollut. 2000;109(2):277–82.

    Google Scholar 

  16. Romero-Ruiz A, Amezcua O, Rodriguez-Ortega MJ, Munoz JL, Alhama J, Rodriguez-Ariza A, et al. Oxidative stress biomarkers in bivalves transplanted to the Guadalquivir estuary after Aznalcollar spill. Environ Toxicol Chem. 2003;22(1):92–100.

    CAS  Google Scholar 

  17. Barata C, Lekumberri I, Vila-Escale M, Prat N, Porte C. Trace metal concentration, antioxidant enzyme activities and susceptibility to oxidative stress in the tricoptera larvae Hydropsyche exocellata from the Llobregat river basin (NE Spain). Aquat Toxicol. 2005;74(1):3–19.

    CAS  Google Scholar 

  18. Ma W, Wang L, He Y, Yan Y. Tissue-specific cadmium and metallothionein levels in freshwater crab Sinopotamon henanense during acute exposure to waterborne cadmium. Environ Toxicol. 2008;23(3):393–400.

    CAS  Google Scholar 

  19. Fang Y, Yang H, Wang T, Liu B, Zhao H, Chen M. Metallothionein and superoxide dismutase responses to sublethal cadmium exposure in the clam Mactra veneriformis. Comp Biochem Physiol Toxicol Pharmacol: CBP. 2010;151(3):325–33.

    Google Scholar 

  20. Ramirez-Bajo MJ, de Atauri P, Ortega F, Westerhoff HV, Gelpi JL, Centelles JJ, et al. Effects of cadmium and mercury on the upper part of skeletal muscle glycolysis in mice. PloS One. 2014;9(1):e80018.

    Google Scholar 

  21. Li L, Tian X, Yu X, Dong S. Effects of acute and chronic heavy metal (Cu, Cd, and Zn) exposure on sea cucumbers (Apostichopus japonicus). BioMed Res Int. 2016;2016:13.

    Google Scholar 

  22. Berg JM, Tymoczko JL, Stryer L. Biochemistry. New York: WH Freeman; 2012.

    Google Scholar 

  23. Luo B, Groenke K, Takors R, Wandrey C, Oldiges M. Simultaneous determination of multiple intracellular metabolites in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle by liquid chromatography–mass spectrometry. J Chromatogr A. 2007;1147(2):153–64.

    CAS  Google Scholar 

  24. Wamelink MM, Struys EA, Jakobs C. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis. 2008;31(6):703–17.

    CAS  Google Scholar 

  25. Santra A, Maiti A, Chowdhury A, Mazumder DN. Oxidative stress in liver of mice exposed to arsenic-contaminated water. Indian J Gastroenterol: Official J Indian Soc Gastroenterol. 2000;19(3):112–5.

    CAS  Google Scholar 

  26. Viselina TN, Luk’yanova ON. Cadmium-induced changes in the activity of carbohydrate metabolism enzymes in mollusks. Russ J Mar Biol. 2000;26(4):289–91.

    Google Scholar 

  27. Rines AK, Sharabi K, Tavares CDJ, Puigserver P. Targeting hepatic glucose metabolism in the treatment of type 2 diabetes. Nat Rev Drug Discov. 2016;15:786.

    CAS  Google Scholar 

  28. Haque M, Roy S, Islam M, Roy N. Role of arsenic on the regulation of glycogen metabolism in liver of Taki fishes (Channa Punctatus) exposed to cold. Thai J Agric Sci. 2009;42(3):159–66.

    Google Scholar 

  29. Reddy S, Venugopal N. In vivo effects of cadmium chloride on certain aspects of protein metabolism in tissues of a freshwater field crab Barytelphusa guerini. Bull Environ Contam Toxicol. 1991;42(6):847–53.

    Google Scholar 

  30. Hazelhoff Roelfzema W, Hacker HJ, Van Noorden CJ. Effects of cadmium exposure on glycogen phosphorylase activity in rat placenta as demonstrated by histochemical means. Histochemistry. 1989;91(4):305–8.. Epub 1989/01/01. eng

    CAS  Google Scholar 

  31. Soengas JL, Agra-Lago MJ, Carballo B, Andres MD, Veira JA. Effect of an acute exposure to sublethal concentrations of cadmium on liver carbohydrate metabolism of Atlantic salmon (Salmo salar). Bull Environ Contam Toxicol. 1996;57(4):625–31.

    CAS  Google Scholar 

  32. Lei LJ, Jin TY, Zhou YF. The toxic effects of cadmium on pancreas. Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi. Chin J Ind Hyg Occup Dis. 2005;23(1):45–9.

    CAS  Google Scholar 

  33. Burzlaff N, Sigel A, Sigel H, Sigel RKO, editors. Cadmium: from toxicity to essentiality, metal ions in life sciences, vol. 11. Dordrecht: Springer; 2013. p. 560. https://doi.org/10.1007/978-94-007-5179-8.

    Book  Google Scholar 

  34. Kalahasthi RB, Hirehal Raghavendra Rao R, Bagalur Krishna Murthy R, Karuna Kumar M. Effect of cadmium exposure on serum amylase activity in cadmium electroplating workers. Environ Bioindic. 2006;1(4):260–7.

    CAS  Google Scholar 

  35. Champe PC, Harvey RA. Biochemistry (Lippincott’s illustrated reviews). Philadelphia: Lippincott; 1994.

    Google Scholar 

  36. Rajanna B, Hobson M, Reese J, Sample E, Chapatwala KD. Chronic hepatic and renal toxicity by cadmium in rats. Drug Chem Toxicol. 1984;7(3):229–41.

    CAS  Google Scholar 

  37. Lucia M, Andre JM, Gonzalez P, Baudrimont M, Bernadet MD, Gontier K, et al. Effect of dietary cadmium on lipid metabolism and storage of aquatic bird Cairina moschata. Ecotoxicology. 2010;19(1):163–70.

    CAS  Google Scholar 

  38. Yang J, Liu D, Jing W, Dahms HU, Wang L. Effects of cadmium on lipid storage and metabolism in the freshwater crab Sinopotamon henanense. PLoS One. 2013;8(10):e77569.

    CAS  Google Scholar 

  39. Digel M, Ehehalt R, Stremmel W, Fullekrug J. Acyl-CoA synthetases: fatty acid uptake and metabolic channeling. Mol Cell Biochem. 2009;326(1–2):23–8.

    CAS  Google Scholar 

  40. Kordinas V, Ioannidis A, Chatzipanagiotou S. The telomere/telomerase system in chronic inflammatory diseases. Cause or effect? Genes. 2016;7(9):60.

    Google Scholar 

  41. Chung JY, Yu SD, Hong YS. Environmental source of arsenic exposure. J Prev Med Public Health (Yebang Uihakhoe chi). 2014;47(5):253–7.

    Google Scholar 

  42. Zhang HN, Yang L, Ling JY, Czajkowsky DM, Wang JF, Zhang XW, et al. Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic. Proc Natl Acad Sci U S A. 2015;112(49):15084–9.

    CAS  Google Scholar 

  43. Tawfik DS, Viola RE. Arsenate replacing phosphate: alternative life chemistries and ion promiscuity. Biochemistry. 2011;50(7):1128–34.

    CAS  Google Scholar 

  44. Dixon HBF. The biochemical action of arsonic acids especially as phosphate analogues. In: Sykes AG, editor. Advances in inorganic chemistry, vol. 44. Cambridge: Academic Press; 1996. p. 191–227.

    Google Scholar 

  45. Xu Y, Ma B, Nussinov R. Structural and functional consequences of phosphate-arsenate substitutions in selected nucleotides: DNA, RNA, and ATP. J Phys Chem B. 2012;116(16):4801–11.

    CAS  Google Scholar 

  46. Tseng CH, Tai TY, Chong CK, Tseng CP, Lai MS, Lin BJ, et al. Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan. Environ Health Perspect. 2000;108(9):847–51.

    CAS  Google Scholar 

  47. Alder JK, Parry EM, Yegnasubramanian S, Wagner CL, Lieblich LM, Auerbach R, et al. Telomere Phenotypes in Females with Heterozygous Mutations in the D yskeratosis Congenita 1 (DKC 1) Gene. Hum Mutat. 2013;34(11):1481–5.

    CAS  Google Scholar 

  48. Kannan GM, Flora SJ. Chronic arsenic poisoning in the rat: treatment with combined administration of succimers and an antioxidant. Ecotoxicol Environ Saf. 2004;58(1):37–43.

    CAS  Google Scholar 

  49. Shi H, Shi X, Liu KJ. Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem. 2004;255(1-2):67–78.

    CAS  Google Scholar 

  50. Naranmandura H, Xu S, Sawata T, Hao WH, Liu H, Bu N, et al. Mitochondria are the main target organelle for trivalent monomethylarsonous acid (MMA(III))-induced cytotoxicity. Chem Res Toxicol. 2011;24(7):1094–103.

    CAS  Google Scholar 

  51. Kligerman AD, Tennant AH. Insights into the carcinogenic mode of action of arsenic. Toxicol Appl Pharmacol. 2007;222(3):281–8.

    CAS  Google Scholar 

  52. Frost SC, Lane MD. Evidence for the involvement of vicinal sulfhydryl groups in insulin-activated hexose transport by 3T3-L1 adipocytes. J Biol Chem. 1985;260(5):2646–52.

    CAS  Google Scholar 

  53. Delnomdedieu M, Basti MM, Otvos JD, Thomas DJ. Reduction and binding of arsenate and dimethylarsinate by glutathione: a magnetic resonance study. Chem-Biol Interact. 1994;90(2):139–55.

    CAS  Google Scholar 

  54. Diaz-Villasenor A, Burns AL, Hiriart M, Cebrian ME, Ostrosky-Wegman P. Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus. Toxicol Appl Pharmacol. 2007;225(2):123–33.

    CAS  Google Scholar 

  55. Wauson EM, Langan AS, Vorce RL. Sodium arsenite inhibits and reverses expression of adipogenic and fat cell-specific genes during in vitro adipogenesis. Toxicol Sci: Official J Soc Toxicol. 2002;65(2):211–9.

    CAS  Google Scholar 

  56. Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN. Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol. 2014;7(2):60–72.

    Google Scholar 

  57. Alissa EM, Ferns GA. Heavy metal poisoning and cardiovascular disease. J Toxicol. 2011;2011:870125.

    Google Scholar 

  58. Rehman K, Fatima F, Waheed I, Akash MSH. Prevalence of exposure of heavy metals and their impact on health consequences. J Cell Biochem. 2018;119(1):157–84.

    CAS  Google Scholar 

  59. Knowles SO, Donaldson WE. Dietary modification of lead toxicity: effects on fatty acid and eicosanoid metabolism in chicks. Comp Biochem Physiol C, Comp Pharmacol Toxicol. 1990;95(1):99–104.

    CAS  Google Scholar 

  60. Patrick L. Lead toxicity part II: the role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity. Altern Med Rev: J Clin Ther. 2006;11(2):114–27.

    Google Scholar 

  61. Flora G, Gupta D, Tiwari A. Toxicity of lead: a review with recent updates. Interdiscip Toxicol. 2012;5(2):47–58.

    CAS  Google Scholar 

  62. Ahamed M, Siddiqui MK. Environmental lead toxicity and nutritional factors. Clin Nutr. 2007;26(4):400–8.

    CAS  Google Scholar 

  63. Quintanilla-Vega B, Hoover D, Bal W, Silbergeld EK, Waalkes MP, Anderson LD. Lead effects on protamine-DNA binding. Am J Ind Med. 2000;38(3):324–9.

    CAS  Google Scholar 

  64. White LD, Cory-Slechta DA, Gilbert ME, Tiffany-Castiglioni E, Zawia NH, Virgolini M, et al. New and evolving concepts in the neurotoxicology of lead. Toxicol Appl Pharmacol. 2007;225(1):1–27.

    CAS  Google Scholar 

  65. Skoczynska A, Poreba R, Sieradzki A, Andrzejak R, Sieradzka U. The impact of lead and cadmium on the immune system. Medycyna Pracy. 2002;53(3):259–64.

    CAS  Google Scholar 

  66. Dietert RR, Piepenbrink MS. Lead and immune function. Crit Rev Toxico. 2006;36(4):359–85.

    CAS  Google Scholar 

  67. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Ann Rev Pharmacol Toxicol. 1998;38:97–120.

    CAS  Google Scholar 

  68. Wei J, Du K, Cai Q, Ma L, Jiao Z, Tan J, et al. Lead induces COX-2 expression in glial cells in a NFAT-dependent, AP-1/NFkappaB-independent manner. Toxicology. 2014;325:67–73.

    CAS  Google Scholar 

  69. Metryka E, Chibowska K, Gutowska I, Falkowska A, Kupnicka P, Barczak K, et al. Lead (Pb) exposure enhances expression of factors associated with inflammation. Int J Mol Sci. 2018;19(6):1813.

    Google Scholar 

  70. Cai L, Li XK, Song Y, Cherian MG. Essentiality, toxicology and chelation therapy of zinc and copper. Curr Med Chem. 2005;12(23):2753–63.

    CAS  Google Scholar 

  71. Wang S, Liu GC, Wintergerst KA, Cai L. Chapter 14 - Metals in diabetes: zinc homeostasis in the metabolic syndrome and diabetes. In: Mauricio D, editor. Molecular nutrition and diabetes. San Diego: Academic Press; 2016. p. 169–82.

    Google Scholar 

  72. Olechnowicz J, Tinkov A, Skalny A, Suliburska J. Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci. 2018;68(1):19–31.

    CAS  Google Scholar 

  73. Hopps E, Noto D, Caimi G, Averna MR. A novel component of the metabolic syndrome: the oxidative stress. Nutr Metab Cardiovasc Dis. 2010;20(1):72–7.

    CAS  Google Scholar 

  74. Ogawa D, Asanuma M, Miyazaki I, Tachibana H, Wada J, Sogawa N, et al. High glucose increases metallothionein expression in renal proximal tubular epithelial cells. Exp Diabetes Res. 2011;2011:534872.

    Google Scholar 

  75. Hadwan MH, Almashhedy LA, Alsalman AR. Study of the effects of oral zinc supplementation on peroxynitrite levels, arginase activity and NO synthase activity in seminal plasma of Iraqi asthenospermic patients. Reprod Biol Endocrinol. 2014;12:1.

    Google Scholar 

  76. Saarni H, Tamminen-Peter L. Physical stress and strain in catering work on the Baltic car ferries. Bull Inst Marit Trop Med Gdynia. 1987;38(1–2):25–31.

    CAS  Google Scholar 

  77. Payahoo L, Ostadrahimi A, Mobasseri M, Khajebishak Y, Asghari Jafarabadi M. Effects of zinc supplementation on serum leptin level and insulin sensitivity in obese people. Trace Elem Electrolytes. 2014;31:27–32.

    CAS  Google Scholar 

  78. Baltaci AK, Mogulkoc R. Leptin and zinc relation: In regulation of food intake and immunity. Indian J Endocrinol Metab. 2012;16(Suppl 3):S611–6.

    Google Scholar 

  79. Briggs DB, Giron RM, Schnittker K, Hart MV, Park CK, Hausrath AC, et al. Zinc enhances adiponectin oligomerization to octadecamers but decreases the rate of disulfide bond formation. Biometals: Int J Role Metal Ions Biol Biochem Med. 2012;25(2):469–86.

    CAS  Google Scholar 

  80. Mazloomi S, Alizadeh N, Aminzare M, Niroomand S, Mousavi SN. Retracted article: serum zinc and adiponectin levels in patients with polycystic ovary syndrome, adjusted for anthropometric, biochemical, dietary intake, and physical activity measures. Biol Trace Element Res. 2018;181(2):388.

    CAS  Google Scholar 

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Acknowledgments

This work has been financially supported by the research grant (8365/Punjab/NRPU/R&D/HEC/2017) received from the Higher Education Commission (HEC) of Pakistan.

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Irshad, K. et al. (2021). Role of Heavy Metals in Metabolic Disorders. In: Akash, M.S.H., Rehman, K., Hashmi, M.Z. (eds) Endocrine Disrupting Chemicals-induced Metabolic Disorders and Treatment Strategies. Emerging Contaminants and Associated Treatment Technologies. Springer, Cham. https://doi.org/10.1007/978-3-030-45923-9_13

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