, Volume 28, Issue 2, pp 231–254 | Cite as

Mercury and metabolic syndrome: a review of experimental and clinical observations

  • Alexey A. Tinkov
  • Olga P. Ajsuvakova
  • Margarita G. Skalnaya
  • Elizaveta V. Popova
  • Anton I. Sinitskii
  • Olga N. Nemereshina
  • Evgenia R. Gatiatulina
  • Alexandr A. Nikonorov
  • Anatoly V. Skalny


A significant interrelation between heavy metal exposure and metabolic syndrome (MetS) development has been demonstrated earlier. Despite the presence of a number of works aimed at the investigation of the role of Hg in MetS development, the existing data remain contradictory. Therefore, the primary objective of the current work is to review the existing data regarding the influence of mercury on universal mechanisms involved in the pathogenesis of the development of MetS and its components. The brief chemical characterization of mercury is provided. The role of mercury in induction of oxidative stress has been discussed. In particular, Hg-induced oxidative stress may occur due to both prooxidant action of the metal and decrease in antioxidant enzymes. Despite the absence of direct indications, it can be proposed that mercury may induce endoplasmic reticulum stress. As it is seen from both in vivo and in vitro studies, mercury is capable of inducing inflammation. The reviewed data demonstrate that mercury affects universal pathogenetic mechanisms of MetS development. Moreover, multiple investigations have indicated the role of mercury in pathogenesis of MetS components: dyslipidemia, hypertension, insulin resistance, and obesity to a lesser extent. The present state of data regarding the interrelation between mercury and MetS denotes the following perspectives: (1) Further clinic-epidemiologic and experimental studies are required to estimate the association between mercury exposure and the development of MetS components, especially obesity; (2) Additional investigations of the possible effect of organism’s mercury content modulation on MetS pathogenesis should be undertaken.


Mercury Toxicity Obesity Insulin resistance Hypertension Dyslipidemia Atherosclerosis 



The authors would like to thank Prof. Richard A. Anderson for helpful discussions and corrections of the manuscript. The current research is supported by Russian Ministry of Education and Science within project No. 2014/258-544.

Conflict of interest

The authors declare no conflict of interest.


  1. Abdel-Hamid HA, Fahmy FC, Sharaf IA (2001) Influence of free radicals on cardiovascular risk due to occupational exposure to mercury. J Egypt Public Health Assoc 76(1–2):53–69PubMedGoogle Scholar
  2. Aguado A, Galán M, Zhenyukh O, Wiggers GA, Roque FR, Redondo S, Peçanha F, Martín A, Fortuño A, Cachofeiro V, Tejerina T, Salaices M, Briones AM (2013) Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways. Toxicol Appl Pharmacol 268(2):188–200PubMedGoogle Scholar
  3. Al-azzawie HF, Umran A, Hyader NH (2013) Oxidative stress, antioxidant status and DNA damage in a mercury exposure workers. Br J of Pharmacol Toxicol 4(3):80–88Google Scholar
  4. Aliaga ME, López-Alarcón C, Barriga G, Olea-Azar C, Speisky H (2010) Redox-active complexes formed during the interaction between glutathione and mercury and/or copper ions. J Inorg Biochem 104(10):1084–1090PubMedGoogle Scholar
  5. Al-Saleh I, Abduljabbar M, Al-Rouqi R, Elkhatib R, Alshabbaheen A, Shinwari N (2013) Mercury (Hg) exposure in breast-fed infants and their mothers and the evidence of oxidative stress. Biol Trace Elem Res 153(1–3):145–154PubMedGoogle Scholar
  6. Ariza ME, Bijur GN, Williams MV (1998) Lead and mercury mutagenesis: role of H2O2, superoxide dismutase, and xanthine oxidase. Environ Mol Mutagen 31(4):352–361PubMedGoogle Scholar
  7. Ayensu WK, Tchounwou PB (2006) Microarray analysis of mercury-induced changes in gene expression in human liver carcinoma (HepG2) cells: importance in immune responses. Int J Environ Res Public Health 3(2):141–173PubMedCentralPubMedGoogle Scholar
  8. Ayotte P, Carrier A, Ouellet N, Boiteau V, Abdous B, Sidi EA, Château-Degat ML, Dewailly É (2011) Relation between methylmercury exposure and plasma paraoxonase activity in inuit adults from Nunavik. Environ Health Perspect 119(8):1077–1083PubMedCentralPubMedGoogle Scholar
  9. Bagger S, Breddam K, Byberg BR (1991) Binding of mercury(II) to protein thiol groups: a study of proteinase K and carboxypeptidase Y. J Inorg Biochem 42(2):97–103PubMedGoogle Scholar
  10. Baldwin AS Jr (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683PubMedGoogle Scholar
  11. Bando I, Reus MI, Andrés D, Cascales M (2005) Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxication. J Biochem Mol Toxicol 19(3):154–161PubMedGoogle Scholar
  12. Bánhegyi G, Baumeister P, Benedetti A, Dong D, Fu Y, Lee AS, Li J, Mao C, Margittai E, Ni M, Paschen W, Piccirella S, Senesi S, Sitia R, Wang M, Yang W (2007) Endoplasmic reticulum stress. Ann N Y Acad Sci 1113:58–71PubMedGoogle Scholar
  13. Barcelos GR, Grotto D, Serpeloni JM, Angeli JP, Rocha BA, de Oliveira Souza VC, Vicentini JT, Emanuelli T, Bastos JK, Antunes LM, Knasmüller S, Barbosa F Jr (2011) Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats. Arch Toxicol 85(9):1151–1157PubMedGoogle Scholar
  14. Barnes DM, Kircher EA (2005) Effects of mercuric chloride on glucose transport in 3T3-L1 adipocytes. Toxicol In Vitro 19(2):207–214PubMedGoogle Scholar
  15. Barnes DM, Hanlon PR, Kircher EA (2003) Effects of inorganic HgCl2 on adipogenesis. Toxicol Sci 75(2):368–377PubMedGoogle Scholar
  16. Bashandy SA, Alhazza IM, El-Desoky GE, Al-Othman ZA (2011) Hepatoprotective and hypolipidemic effects of spirulina platensis in rats administered mercuric chloride. Afr J Pharm Pharmacol 5(2):175–182Google Scholar
  17. Basseri S, Austin RC (2012) Endoplasmic reticulum stress and lipid metabolism: mechanisms and therapeutic potential. Biochem Res Int 2012:841362. doi: 10.1155/2012/841362 PubMedCentralPubMedGoogle Scholar
  18. Bautista LE, Stein JH, Morgan BJ, Stanton N, Young T, Nieto FJ (2009) Association of blood and hair mercury with blood pressure and vascular reactivity. WMJ 108(5):250–252PubMedGoogle Scholar
  19. Beltrán-Sánchez H, Harhay MO, Harhay MM, McElligott S (2013) Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. J Am Coll Cardiol 62(8):697–703PubMedCentralPubMedGoogle Scholar
  20. Bender M, Lymberidi-Settimo E, Groth E (2013) New mercury treaty exposes health risks. J Public Health Policy 35(1):1–13PubMedGoogle Scholar
  21. Benov LC, Benchev IC, Monovich OH (1990) Thiol antidotes effect on lipid peroxidation in mercury-poisoned rats. Chem Biol Interact 76(3):321–332PubMedGoogle Scholar
  22. Black RS, Whanger PD, Tripp MJ (1979) Influence of silver, mercury, lead, cadmium, and selenium on glutathione peroxidase and transferase activities in rats. Biol Trace Elem Res 1(4):313–324PubMedGoogle Scholar
  23. Bloom GD, Hellman B, Idahl LA, Lernmark A, Sehlin J, Täljedal IB (1972) Effects of organic mercurials on mammalian pancreatic -cells. Insulin release, glucose transport, glucose oxidation, membrane permeability and ultrastructure. Biochem J 129(2):241–254PubMedCentralPubMedGoogle Scholar
  24. Bracci M, Tomasetti M, Malavolta M, Bonacucina V, Mocchegiani E, Santarelli L (2008) L-arginine reduces mercury accumulation in thymus of mercury-exposed mice: role of nitric oxide synthase activity and metallothioneins. Ind Health 46(6):567–574PubMedGoogle Scholar
  25. Bramanti E, D’Ulivo A, Lampugnani L, Zamboni R, Raspi G (1999) Application of mercury cold vapor atomic fluorescence spectrometry to the characterization of mercury-accessible-SH groups in native proteins. Anal Biochem 274(2):163–173PubMedGoogle Scholar
  26. Branco V, Canário J, Lu J, Holmgren A, Carvalho C (2011) Mercury and selenium interaction in vivo: effects on thioredoxin reductase and glutathione peroxidase. Free Radic Biol Med 52(4):781–793PubMedGoogle Scholar
  27. Brenden N, Rabbani H, Abedi-Valugerdi M (2001) Analysis of mercury-induced immune activation in nonobese diabetic (NOD) mice. Clin Exp Immunol 125(2):202–210PubMedCentralPubMedGoogle Scholar
  28. Cameron AJ, Shaw JE, Zimmet PZ (2004) The metabolic syndrome: prevalence in worldwide populations. Endocrinol Metab Clin North Am 33(2):351–375PubMedGoogle Scholar
  29. Carranza-Rosales P, Said-Fernández S, Sepúlveda-Saavedra J, Cruz-Vega DE, Gandolfi AJ (2005) Morphologic and functional alterations induced by low doses of mercuric chloride in the kidney OK cell line: ultrastructural evidence for an apoptotic mechanism of damage. Toxicology 210(2–3):111–121PubMedGoogle Scholar
  30. Carvalho CM, Chew EH, Hashemy SI, Lu J, Holmgren A (2008) Inhibition of the human thioredoxin system. A molecular mechanism of mercury toxicity. J Biol Chem 283(18):11913–11923PubMedGoogle Scholar
  31. Carvalho CM, Lu J, Zhang X, Arnér ES, Holmgren A (2010) Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning. FASEB J 25(1):370–381PubMedGoogle Scholar
  32. Cave M, Appana S, Patel M, Falkner KC, McClain CJ, Brock G (2010) Polychlorinated biphenyls, lead, and mercury are associated with liver disease in American adults: NHANES 2003–2004. Environ Health Perspect 118(12):1735–1742PubMedCentralPubMedGoogle Scholar
  33. Ceriello A, Motz E (2004) Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 24(5):816–823PubMedGoogle Scholar
  34. Chang JY, Tsai PF (2008) Prevention of methylmercury-induced mitochondrial depolarization, glutathione depletion and cell death by 15-deoxy-delta-12,14-prostaglandin J(2). Neurotoxicology 29(6):1054–1061PubMedCentralPubMedGoogle Scholar
  35. Chang JW, Chen HL, Su HJ, Liao PC, Guo HR, Lee CC (2011) Simultaneous exposure of non-diabetics to high levels of dioxins and mercury increases their risk of insulin resistance. J Hazard Mater 185(2–3):749–755PubMedGoogle Scholar
  36. Chen C, Qu L, Li B, Xing L, Jia G, Wang T, Gao Y, Zhang P, Li M, Chen W, Chai Z (2005) Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2′-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury. Clin Chem 51(4):759–767PubMedGoogle Scholar
  37. Chen C, Qu L, Zhao J, Liu S, Deng G, Li B, Zhang P, Chai Z (2006a) Accumulation of mercury, selenium and their binding proteins in porcine kidney and liver from mercury-exposed areas with the investigation of their redox responses. Sci Total Environ 366(2–3):627–637PubMedGoogle Scholar
  38. Chen C, Yu H, Zhao J, Li B, Qu L, Liu S, Zhang P, Chai Z (2006b) The roles of serum selenium and selenoproteins on mercury toxicity in environmental and occupational exposure. Environ Health Perspect 114(2):297–301PubMedCentralPubMedGoogle Scholar
  39. Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH (2006c) Methylmercury induces pancreatic beta-cell apoptosis and dysfunction. Chem Res Toxicol 19(8):1080–1085PubMedGoogle Scholar
  40. Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH (2006d) The role of phosphoinositide 3-kinase/Akt signaling in low-dose mercury-induced mouse pancreatic beta-cell dysfunction in vitro and in vivo. Diabetes 55(6):1614–1624PubMedGoogle Scholar
  41. Chen YW, Huang CF, Yang CY, Yen CC, Tsai KS, Liu SH (2010) Inorganic mercury causes pancreatic beta-cell death via the oxidative stress-induced apoptotic and necrotic pathways. Toxicol Appl Pharmacol 243(3):323–331PubMedGoogle Scholar
  42. Cho S, Jacobs DR Jr, Park K (2014) Population correlates of circulating mercury levels in Korean adults: the Korea National Health and Nutrition Examination Survey IV. BMC Public Health 14:527PubMedCentralPubMedGoogle Scholar
  43. Choi B, Yeum KJ, Park SJ, Kim KN, Joo NS (2013) Elevated serum ferritin and mercury concentrations are associated with hypertension; analysis of the fourth and fifth Korea national health and nutrition examination survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). Environ Toxicol. doi: 10.1002/tox.21899 Google Scholar
  44. Cnop M, Foufelle F, Velloso LA (2012) Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med 18(1):59–68PubMedGoogle Scholar
  45. Cotton FA, Wilkinson G, Murillo CA, Bochmann M (1999) Advanced Inorganic Chemistry, 6th edn. Wiley-Interscience, Newyork, p 1376Google Scholar
  46. Cuello S, Gobbya L, Madrid Y, Campuzano S, Pedrero M, Bravo L, Cámara C, Ramos S (2010) Molecular mechanisms of methylmercury-induced cell death in human HepG2 cells. Food Chem Toxicol 48(5):1405–1411PubMedGoogle Scholar
  47. Da Cunha V, Souza HP, Rossoni LV, França AS, Vassallo DV (2000) Effects of mercury on the isolated perfused rat tail vascular bed are endothelium-dependent. Arch Environ Contam Toxicol 39(1):124–130PubMedGoogle Scholar
  48. Dastych J, Walczak-Drzewiecka A, Wyczolkowska J, Metcalfe DD (1999) Murine mast cells exposed to mercuric chloride release granule-associated N-acetyl-beta-D-hexosaminidase and secrete IL-4 and TNF-alpha. J Allergy Clin Immunol 103(6):1108–1114PubMedGoogle Scholar
  49. De Freitas AS, Funck VR, Rotta Mdos S, Bohrer D, Mörschbächer V, Puntel RL, Nogueira CW, Farina M, Aschner M, Rocha JB (2009) Diphenyl diselenide, a simple organoselenium compound, decreases methylmercury-induced cerebral, hepatic and renal oxidative stress and mercury deposition in adult mice. Brain Res Bull 79(1):77–84PubMedGoogle Scholar
  50. De Vos G, Jerschow E, Liao Z, Rosenstreich D (2004) Effects of fluoride and mercury on human cytokine response in vitro. J Allergy Clin Immunol 113(2):S66Google Scholar
  51. De Vos G, Abotaga S, Liao Z, Jerschow E, Rosenstreich D (2007) Selective effect of mercury on Th2-type cytokine production in humans. Immunopharmacol Immunotoxicol 29(3–4):537–548PubMedGoogle Scholar
  52. Drescher O, Dewailly E, Diorio C, Ouellet N, Sidi EA, Abdous B, Valera B, Ayotte P (2014) Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults. J Expo Sci Environ Epidemiol. doi: 10.1038/jes.2013.96 PubMedGoogle Scholar
  53. Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365(9468):1415–1428PubMedGoogle Scholar
  54. Eliav E, Kaldor U, Ishikawa Y (1995) Transition energies of mercury and ekamercury (element 112) by the relativistic coupled-cluster method. Phys Rev A 52(4):2765–2769PubMedGoogle Scholar
  55. Eom SY, Choi SH, Ahn SJ, Kim DK, Kim DW, Lim JA, Choi BS, Shin HJ, Yun SW, Yoon HJ, Kim YM, Hong YS, Yun YW, Sohn SJ, Kim H, Park KS, Pyo HS, Kim H, Oh SY, Kim J, Lee SA, Ha M, Kwon HJ, Park JD (2014) Reference levels of blood mercury and association with metabolic syndrome in Korean adults. Int Arch Occup Environ Health 87(5):501–513PubMedGoogle Scholar
  56. Ezaki O (1989) IIb group metal ions (Zn2 + , Cd2 + , Hg2 +) stimulate glucose transport activity by post-insulin receptor kinase mechanism in rat adipocytes. J Biol Chem 264(27):16118–16122PubMedGoogle Scholar
  57. Farina M, Soares FA, Zeni G, Souza DO, Rocha JB (2004) Additive pro-oxidative effects of methylmercury and ebselen in liver from suckling rat pups. Toxicol Lett 146(3):227–235PubMedGoogle Scholar
  58. Farina M, Campos F, Vendrell I, Berenguer J, Barzi M, Pons S, Suñol C (2009) Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells. Toxicol Sci 112(2):416–426PubMedGoogle Scholar
  59. Faustman EM, Ponce RA, Ou YC, Mendoza MA, Lewandowski T, Kavanagh T (2002) Investigations of methylmercury-induced alterations in neurogenesis. Environ Health Perspect 110(5):859–864PubMedCentralPubMedGoogle Scholar
  60. Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel-Soto J, Morales-González A, Esquivel-Chirino C, Durante-Montiel I, Sánchez-Rivera G, Valadez-Vega C, Morales-González JA (2011) Inflammation, oxidative stress, and obesity. Int J Mol Sci 12(5):3117–3132PubMedCentralPubMedGoogle Scholar
  61. Fillion M, Mergler D, Sousa Passos CJ, Larribe F, Lemire M, Guimarães JR (2006) A preliminary study of mercury exposure and blood pressure in the Brazilian Amazon. Environ Health 5:29PubMedCentralPubMedGoogle Scholar
  62. Flores CR, Puga MP, Wrobel K, Garay Sevilla ME, Wrobel K (2011) Trace elements status in diabetes mellitus type 2: possible role of the interaction between molybdenum and copper in the progress of typical complications. Diabetes Res Clin Pract 91(3):333–341PubMedGoogle Scholar
  63. Franco JL, Posser T, Dunkley PR, Dickson PW, Mattos JJ, Martins R, Bainy AC, Marques MR, Dafre AL, Farina M (2009) Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase. Free Radic Biol Med 47(4):449–457PubMedGoogle Scholar
  64. Friend A, Craig L, Turner S (2013) The prevalence of metabolic syndrome in children: a systematic review of the literature. Metab Syndr Relat Disord 11(2):71–80PubMedGoogle Scholar
  65. Furieri LB, Galán M, Avendaño MS, García-Redondo AB, Aguado A, Martínez S, Cachofeiro V, Bartolomé MV, Alonso MJ, Vassallo DV, Salaices M (2011) Endothelial dysfunction of rat coronary arteries after exposure to low concentrations of mercury is dependent on reactive oxygen species. Br J Pharmacol 162(8):1819–1831PubMedCentralPubMedGoogle Scholar
  66. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114(12):1752–1761PubMedCentralPubMedGoogle Scholar
  67. Futatsuka M, Kitano T, Wakamiya J (1996) An epidemiological study on diabetes mellitus in the population living in a methyl mercury polluted area. J Epidemiol 6(4):204–208PubMedGoogle Scholar
  68. García-Sevillano MA, García-Barrera T, Navarro F, Gómez-Ariza JL (2014) Absolute quantification of superoxide dismutase in cytosol and mitochondria of mice hepatic cells exposed to mercury by a novel metallomic approach. Anal Chim Acta. doi: 10.1016/j.aca.2014.07.014 PubMedGoogle Scholar
  69. Gardner RM, Nyland JF, Evans SL, Wang SB, Doyle KM, Crainiceanu CM, Silbergeld EK (2009) Mercury induces an unopposed inflammatory response in human peripheral blood mononuclear cells in vitro. Environ Health Perspect 117(12):1932–1938PubMedCentralPubMedGoogle Scholar
  70. Gardner RM, Nyland JF, Silbergeld EK (2010a) Differential immunotoxic effects of inorganic and organic mercury species in vitro. Toxicol Lett 198(2):182–190PubMedCentralPubMedGoogle Scholar
  71. Gardner RM, Nyland JF, Silva IA, Ventura AM, de Souza JM, Silbergeld EK (2010b) Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: a cross-sectional study. Environ Res 110(4):345–354PubMedCentralPubMedGoogle Scholar
  72. George JM (1971) Effect of mercury on response of isolated fat cells to insulin and lipolytic hormones. Endocrinology 89(6):1489–1498PubMedGoogle Scholar
  73. Ghosh R, Jana AD, Pal S, Mostafa G, Fun HK, Ghosh BK (2007) Crystal engineering through [Hg (SCN)4]2−templates: SS interaction mediated 3-D parallel interpenetration in the self-assembled superstructure of [Hg (SCN)4]2−and protonated 2, 2′-dipyridylamine. CrystEngComm 9(5):353–357Google Scholar
  74. Gillespie RJ (1972) Molecular Geometry. Van Nostrand Reinhold, LondonGoogle Scholar
  75. Gillespie RJ, Granger P, Morgan KR, Schrobilgen GJ (1984) Mercury-199 NMR study of the mercury cations (Hg2+, Hg22+, Hg32+, and Hg42+): the first example of mercury-mercury spin-spin coupling. Inorg Chem 23(7):887–891Google Scholar
  76. Goering PL, Thomas D, Rojko JL, Lucas AD (1999) Mercuric chloride-induced apoptosis is dependent on protein synthesis. Toxicol Lett 105(3):183–195PubMedGoogle Scholar
  77. Golpon HA, Püchner A, Barth P, Welte T, Wichert PV, Feddersen CO (2003) Nitric oxide-dependent vasorelaxation and endothelial cell damage caused by mercury chloride. Toxicology 192(2–3):179–188PubMedGoogle Scholar
  78. Gradinaru R, Ionas A, Pui A, Zbancioc G, Drochioiu G (2011) Interaction of inorganic mercury with CoA-SH and acyl-CoAs. Biometals 24(6):1115–1121PubMedGoogle Scholar
  79. Grdenic D (1965) The structural chemistry of mercury. Quarterly Reviews, Chemical Society 19(3):303–328Google Scholar
  80. Greenwood NN, Earnshaw A (1997) Chemistry of the Elements. Elsevier, AmsterdamGoogle Scholar
  81. Grotto D, Valentini J, Fillion M, Passos CJ, Garcia SC, Mergler D, Barbosa FJr (2010) Mercury exposure and oxidative stress in communities of the Brazilian Amazon. Sci Total Environ 408(4):806–811PubMedGoogle Scholar
  82. Gump BB, MacKenzie JA, Dumas AK, Palmer CD, Parsons PJ, Segu ZM, Mechref YS, Bendinskas KG (2012) Fish consumption, low-level mercury, lipids, and inflammatory markers in children. Environ ResJa 112:204–211Google Scholar
  83. Hagele TJ, Mazerik JN, Gregory A, Kaufman B, Magalang U, Kuppusamy ML, Marsh CB, Kuppusamy P, Parinandi NL (2007) Mercury activates vascular endothelial cell phospholipase D through thiols and oxidative stress. Int J Toxicol 26(1):57–69PubMedGoogle Scholar
  84. Hansen JM, Zhang H, Jones DP (2006) Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metal ions. Free Radic Biol Med 40(1):138–145PubMedGoogle Scholar
  85. He X, Liang M (2013) Shortening of mitochondria and dilation of endoplasmic reticulum in the medullary thick ascending limb of dahl salt-sensitive rats. Hypertension 62:A479Google Scholar
  86. He K, Xun P, Liu K, Morris S, Reis J, Guallar E (2013) Mercury exposure in young adulthood and incidence of diabetes later in life: the CARDIA Trace Element Study. Diabetes Care 36(6):1584–1589PubMedCentralPubMedGoogle Scholar
  87. Hemdan NY, Lehmann I, Wichmann G, Lehmann J, Emmrich F, Sack U (2007) Immunomodulation by mercuric chloride in vitro: application of different cell activation pathways. Clin Exp Immunol 148(2):325–337PubMedCentralPubMedGoogle Scholar
  88. Hijova E, Nistiar F, Sipulova A (2005) Changes in ascorbic acid and malondialdehyde in rats after exposure to mercury. Bratisl Lek Listy 106(8–9):248–251PubMedGoogle Scholar
  89. Hirota Y, Yamaguchi S, Shimojoh N, Sano KI (1980) Inhibitory effect of methylmercury on the activity of glutathione peroxidase. Toxicol Appl Pharmacol 53(1):174–176PubMedGoogle Scholar
  90. Hoffman M, Autor AP (1980) Production of superoxide anion by an NADPH-oxidase from rat pulmonary macrophages. FEBS Lett 121(2):352–354PubMedGoogle Scholar
  91. Holmgren A, Lu J (2010) Thioredoxin and thioredoxin reductase: current research with special reference to human disease. Biochem Biophys Res Commun 396(1):120–124PubMedGoogle Scholar
  92. Hong D, Cho SH, Park SJ, Kim SY, Park SB (2013) Hair mercury level in smokers and its influence on blood pressure and lipid metabolism. Environ Toxicol Pharmacol 36(1):103–107PubMedGoogle Scholar
  93. Hu H, Abedi-Valugerdi M, Möller G (1997) Pretreatment of lymphocytes with mercury in vitro induces a response in T cells from genetically determined low-responders and a shift of the interleukin profile. Immunology 90(2):198–204PubMedCentralPubMedGoogle Scholar
  94. Huang YL, Cheng SL, Lin TH (1996) Lipid peroxidation in rats administrated with mercuric chloride. Biol Trace Elem Res 52(2):193–206PubMedGoogle Scholar
  95. Ibrahim S (2011) Effect of methylmercury on insulin-stimulated glucose uptake in mouse skeletal muscle. Diabetologia 54:227Google Scholar
  96. Jaiswal N, Rizvi SI (2013) Onion extract (Allium cepa L.) up-regulates paraoxonase 1 activity with concomitant protection against LDL oxidation in male wistar strain rats subjected to mercuric chloride induced oxidative stress. Planta Med 79:PB21Google Scholar
  97. James SJ, Slikker W 3rd, Melnyk S, New E, Pogribna M, Jernigan S (2005) Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. Neurotoxicology 26(1):1–8PubMedGoogle Scholar
  98. Kang D, Lee K (2013) The relationships between blood Mercury concentration and body composition measures using 2010 Korean National Health and Nutrition Examination Survey. Korean J Obes 22(4):237–242Google Scholar
  99. Kassi E, Pervanidou P, Kaltsas G, Chrousos G (2011) Metabolic syndrome: definitions and controversies. BMC Med 9:48PubMedCentralPubMedGoogle Scholar
  100. Kawakami T, Hanao N, Nishiyama K, Kadota Y, Inoue M, Sato M, Suzuki S (2012) Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice. Toxicol Appl Pharmacol 258(1):32–42PubMedGoogle Scholar
  101. Keizo W, Yasuo N (1979) Toxic effects of several mercury compounds on SH and non-SH enzymes. Toxicol Lett 4(1):49–55Google Scholar
  102. Kempuraj D, Asadi S, Zhang B, Manola A, Hogan J, Peterson E, Theoharides TC (2010) Mercury induces inflammatory mediator release from human mast cells. J Neuroinflammation 7:20PubMedCentralPubMedGoogle Scholar
  103. Kim SH, Sharma RP (2005) Mercury alters endotoxin-induced inflammatory cytokine expression in liver: differential roles of p38 and extracellular signal-regulated mitogen-activated protein kinases. Immunopharmacol Immunotoxicol 27(1):123–135PubMedGoogle Scholar
  104. Kim SH, Johnson VJ, Sharma RP (2002) Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage: differential modulation of NF-kappaB and p38 MAPK signaling pathways. Nitric Oxide 7(1):67–74PubMedGoogle Scholar
  105. Kim SH, Johnson VJ, Sharma RP (2003) Oral exposure to inorganic mercury alters T lymphocyte phenotypes and cytokine expression in BALB/c mice. Arch Toxicol 77(11):613–620PubMedGoogle Scholar
  106. Kitamura M, Hiramatsu N (2010) The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity. Biometals 23(5):941–950PubMedGoogle Scholar
  107. Kobal AB, Horvat M, Prezelj M, Briski AS, Krsnik M, Dizdarevic T, Mazej D, Falnoga I, Stibilj V, Arneric N, Kobal D, Osredkar J (2004) The impact of long-term past exposure to elemental mercury on antioxidative capacity and lipid peroxidation in mercury miners. J Trace Elem Med Biol 17(4):261–274PubMedGoogle Scholar
  108. Kobal AB, Prezelj M, Horvat M, Krsnik M, Gibicar D, Osredkar J (2008) Glutathione level after long-term occupational elemental mercury exposure. Environ Res 107(1):115–123PubMedGoogle Scholar
  109. Kondo T, Osugi S, Shimokata K, Honjo H, Morita Y, Yamashita K, Maeda K, Muramatsu T, Shintani S, Matsushita K, Murohara T (2011) Metabolic syndrome and all-cause mortality, cardiac events, and cardiovascular events: a follow-up study in 25,471 young- and middle-aged Japanese men. Eur J Cardiovasc Prev Rehabil 18(4):574–580PubMedGoogle Scholar
  110. Kumagai Y, Homma-Takeda S, Shinyashiki M, Shimojo N (1997a) Alterations in superoxide dismutase isozymes by methylmercury. Appl Organomet Chem 11(8):635–643Google Scholar
  111. Kumagai Y, Nagafune J, Mizukado S, Shinyashiki M, Shimojo N (1997b) 3C-03 alterations in gene expression, protein content and enzyme activity of mouse kidney Mn-SOD by inorganic mercury. J Toxicol Sci 22(4):372Google Scholar
  112. Kunkely H, Vogler A (1989) Photoluminescence of tetranuclear mercury (II) complexes. Chem Phys Lett 164(6):621–624Google Scholar
  113. Kuo CC, Moon K, Thayer KA, Navas-Acien A (2013) Environmental chemicals and type 2 diabetes: an updated systematic review of the epidemiologic evidence. Curr Diab Rep 13(6):831–849PubMedCentralPubMedGoogle Scholar
  114. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288(21):2709–2716PubMedGoogle Scholar
  115. Lamborg CH, Hammerschmidt CR, Bowman KL, Swarr GJ, Munson K, Ohnemus DC, Saito MA (2014) A global ocean inventory of anthropogenic mercury based on water column measurements. Nature 512(7512):65–68PubMedGoogle Scholar
  116. Lee AS (2005) The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 35(4):373–381PubMedGoogle Scholar
  117. Lee BK, Kim Y (2013) Blood cadmium, mercury, and lead and metabolic syndrome in South Korea: 2005–2010 Korean National Health and Nutrition Examination Survey. Am J Ind Med 56(6):682–692PubMedGoogle Scholar
  118. Lee YW, Ha MS, Kim YK (2001) Role of reactive oxygen species and glutathione in inorganic mercury-induced injury in human glioma cells. Neurochem Res 26(11):1187–1193PubMedGoogle Scholar
  119. Lim S, Choi MC, Joh KO, Paek D (2008) The health effects of mercury on the cardiac autonomic activity according to the heart rate variability. Korean J Occup Environ Med 20(4):302–313Google Scholar
  120. Lin TH, Huang YL, Huang SF (1996) Lipid peroxidation in liver of rats administrated with methyl mercuric chloride. Biol Trace Elem Res 54(1):33–41PubMedGoogle Scholar
  121. Lind PM, Risérus U, Salihovic S, Bavel BV, Lind L (2013) An environmental wide association study (EWAS) approach to the metabolic syndrome. Environ Int 55:1–8PubMedGoogle Scholar
  122. Lison D, Dubois P, Lauwerys R (1988) In vitro effect of mercury and vanadium on superoxide anion production and plasminogen activator activity of mouse peritoneal macrophages. Toxicol Lett 40(1):29–36PubMedGoogle Scholar
  123. Liu SH, Lin-Shiau SY (2002) Mercuric chloride alters the membrane potential and intracellular calcium level in mouse pancreatic islet cells. J Toxicol Environ Health A 65(3–4):317–326PubMedGoogle Scholar
  124. Liu J, Lei D, Waalkes MP, Beliles RP, Morgan DL (2003) Genomic analysis of the rat lung following elemental mercury vapor exposure. Toxicol Sci 74(1):174–181PubMedGoogle Scholar
  125. Liu H, Qian J, Wang F, Sun X, Xu X, Xu W, Zhang X, Zhang X (2010) Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication. Eye (Lond) 24(1):137–144Google Scholar
  126. Lund BO, Miller DM, Woods JS (1991) Mercury-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria. Biochem Pharmacol 42(S1):81–87Google Scholar
  127. Machado AC, Padilha AS, Wiggers GA, Siman FD, Stefanon I, Vassallo DV (2007) Small doses of mercury increase arterial pressure reactivity to phenylephrine in rats. Environ Toxicol Pharmacol 24(2):92–97PubMedGoogle Scholar
  128. Mackness M, Mackness B (2004) Paraoxonase 1 and atherosclerosis: is the gene or the protein more important? Free Radic Biol Med 37(9):1317–1323PubMedGoogle Scholar
  129. Mah V, Jalilehvand F (2010) Glutathione complex formation with mercury(II) in aqueous solution at physiological pH. Chem Res Toxicol 23(11):1815–1823PubMedCentralPubMedGoogle Scholar
  130. Mahboob M, Shireen KF, Atkinson A, Khan AT (2001) Lipid peroxidation and antioxidant enzyme activity in different organs of mice exposed to low level of mercury. J Environ Sci Health B 36(5):687–697PubMedGoogle Scholar
  131. Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, Williams GR (2004) Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 110(10):1245–1250PubMedGoogle Scholar
  132. Matsuda M, Shimomura I (2013) Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract 7(5):e330–e341PubMedGoogle Scholar
  133. Matsuzawa-Nagata N, Takamura T, Ando H, Nakamura S, Kurita S, Misu H, Ota T, Yokoyama M, Honda M, Miyamoto K, Kaneko S (2008) Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. Metabolism 57(8):1071–1077PubMedGoogle Scholar
  134. Mazerik JN, Mikkilineni H, Kuppusamy VA, Steinhour E, Peltz A, Marsh CB, Kuppusamy P, Parinandi NL (2007) Mercury activates phospholipase a(2) and induces formation of arachidonic acid metabolites in vascular endothelial cells. Toxicol Mech Methods 17(9):541–557PubMedGoogle Scholar
  135. McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244(22):6049–6055PubMedGoogle Scholar
  136. Meltzer HM, Mundal HH, Alexander J, Bibow K, Ydersbond TA (1994) Does dietary arsenic and mercury affect cutaneous bleeding time and blood lipids in humans? Biol Trace Elem Res 46(1–2):135–153PubMedGoogle Scholar
  137. Merzoug S, Toumi ML, Oumeddour A, Boukhris N, Baudin B, Tahraoui A, Bairi A (2009) Effect of inorganic mercury on biochemical parameters in Wistar rat. Journal of cell and Animal Biology 3(12):222–230Google Scholar
  138. Milaeva E, Petrosyan V, Berberova N, Pimenov Y, Pellerito L (2004) Organic derivatives of mercury and tin as promoters of membrane lipid peroxidation. Bioinorg Chem Appl 2(1–2):69–91PubMedCentralGoogle Scholar
  139. Miller DM, Woods JS (1993) Redox activities of mercury-thiol complexes: implications for mercury-induced porphyria and toxicity. Chem Biol Interact 88(1):23–35PubMedGoogle Scholar
  140. Moon SS (2013) Association of lead, mercury and cadmium with diabetes in the Korean population: the Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010. Diabet Med 30(4):e143–e148PubMedGoogle Scholar
  141. Moon S (2014) Additive effect of heavy metals on metabolic syndrome in the Korean population: the Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010. Endocrine 46(2):263–271PubMedGoogle Scholar
  142. Moreira EL, de Oliveira J, Dutra MF, Santos DB, Gonçalves CA, Goldfeder EM, de Bem AF, Prediger RD, Aschner M, Farina M (2012) Does methylmercury-induced hypercholesterolemia play a causal role in its neurotoxicity and cardiovascular disease? Toxicol Sci 30(2):373–382Google Scholar
  143. Mozaffarian D, Shi P, Morris JS, Grandjean P, Siscovick DS, Spiegelman D, Willett WC, Rimm EB, Curhan GC, Forman JP (2012) Mercury exposure and risk of hypertension in US men and women in 2 prospective cohorts. Hypertension 60(3):645–652PubMedCentralPubMedGoogle Scholar
  144. Mozumdar A, Liguori G (2011) Persistent increase of prevalence of metabolic syndrome among U.S. adults: NHANES III to NHANES 1999-2006. Diabetes Care 34(1):216–219PubMedCentralPubMedGoogle Scholar
  145. Mykkanen HM, Ganther HE (1974) Effect of mercury on erythrocyte glutathione reductase activity. In vivo and in vitro studies. Bull Environ Contam Toxicol 12(1):10–16PubMedGoogle Scholar
  146. Nakagawa R (1995) Concentration of mercury in hair of diseased people in Japan. Chemosphere 30(1):135–140PubMedGoogle Scholar
  147. Nasu T, Nakai E, Gyobu K, Ishida Y (1984) Relaxant effects of mercury and mercury uptake in the smooth muscle of guinea-pig taenia coli. Gen Pharmacol 15(3):247–250PubMedGoogle Scholar
  148. Ni M, Li X, Yin Z, Jiang H, Sidoryk-Wegrzynowicz M, Milatovic D, Cai J, Aschner M (2010) Methylmercury induces acute oxidative stress, altering Nrf2 protein level in primary microglial cells. Toxicol Sci 116(2):590–603PubMedCentralPubMedGoogle Scholar
  149. Nyland JF, Fillion M, Barbosa F Jr, Shirley DL, Chine C, Lemire M, Mergler D, Silbergeld EK (2011) Biomarkers of methylmercury exposure immunotoxicity among fish consumers in Amazonian Brazil. Environ Health Perspect 119(12):1733–1738PubMedCentralPubMedGoogle Scholar
  150. Oda E (2012) Metabolic syndrome: its history, mechanisms, and limitations. Acta Diabetol 49(2):89–95PubMedGoogle Scholar
  151. Omanwar S, Saidullah B, Ravi K, Fahim M (2013) Modulation of vasodilator response via the nitric oxide pathway after acute methyl mercury chloride exposure in rats. Biomed Res Int 2013:530603PubMedCentralPubMedGoogle Scholar
  152. Oram PD, Fang X, Fernando Q, Letkeman P, Letkeman D (1996) The formation of constants of mercury(II)–glutathione complexes. Chem Res Toxicol 9(4):709–712PubMedGoogle Scholar
  153. Ou YC, Thompson SA, Kirchner SC, Kavanagh TJ, Faustman EM (1997) Induction of growth arrest and DNA damage-inducible genes Gadd45 and Gadd153 in primary rodent embryonic cells following exposure to methylmercury. Toxicol Appl Pharmacol 147(1):31–38PubMedGoogle Scholar
  154. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH, Hotamisligil GS (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306(5695):457–461PubMedGoogle Scholar
  155. Pal S, Blais JM, Robidoux MA, Haman F, Krümmel E, Seabert TA, Imbeault P (2013) The association of type 2 diabetes and insulin resistance/secretion with persistent organic pollutants in two First Nations communities in northern Ontario. Diabetes Metab 39(6):497–504PubMedGoogle Scholar
  156. Parikh RM, Mohan V (2012) Changing definitions of metabolic syndrome. Indian J Endocrinol Metab 16(1):7–12PubMedCentralPubMedGoogle Scholar
  157. Park S, Lee BK (2013) Body fat percentage and hemoglobin levels are related to blood lead, cadmium, and mercury concentrations in a Korean Adult Population (KNHANES 2008–2010). Biol Trace Elem Res 151(3):315–323PubMedGoogle Scholar
  158. Park HJ, Youn HS (2013) Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase. Toxicol Ind Health 29(2):169–174PubMedGoogle Scholar
  159. Park SB, Choi SW, Nam AY (2009) Hair tissue mineral analysis and metabolic syndrome. Biol Trace Elem Res 130(3):218–228PubMedGoogle Scholar
  160. Park SK, Lee S, Basu N, Franzblau A (2013) Associations of blood and urinary mercury with hypertension in U.S. adults: the NHANES 2003-2006. Environ Res 123:25–32PubMedCentralPubMedGoogle Scholar
  161. Pearson RG (1963) Hard and soft acids and bases. J Am Chem Soc 85(22):3533–3539Google Scholar
  162. Pearson RG (1968) Hard and soft acids and bases, HSAB, part 1: fundamental principles. J Chem Educ 45(9):581Google Scholar
  163. Pecanha FM, Wiggers GA, Briones AM, Perez-Giron JV, Miguel M, Garcia-Redondo AB, Vassallo DV, Alonso MJ, Salaices M (2010) The role of cyclooxygenase (COX)-2 derived prostanoids on vasoconstrictor responses to phenylephrine is increased by exposure to low mercury concentration. J Physiol Pharmacol 61(1):29–36PubMedGoogle Scholar
  164. Pedersen EB, Jørgensen ME, Pedersen MB, Siggaard C, Sørensen TB, Mulvad G, Hansen JC, Asmund G, Skjoldborg H (2005) Relationship between mercury in blood and 24-h ambulatory blood pressure in Greenlanders and Danes. Am J Hypertens 18(5 Pt 1):612–618PubMedGoogle Scholar
  165. Peltz A, Sherwani SI, Kotha SR, Mazerik JN, O’Connor Butler ES, Kuppusamy ML, Hagele T, Magalang UJ, Kuppusamy P, Marsh CB, Parinandi NL (2009) Calcium and calmodulin regulate mercury-induced phospholipase D activation in vascular endothelial cells. Int J Toxicol 28(3):190–206PubMedGoogle Scholar
  166. Perrin-Nadif R, Dusch M, Koch C, Schmitt P, Mur JM (1996) Catalase and superoxide dismutase activities as biomarkers of oxidative stress in workers exposed to mercury vapors. J Toxicol Environ Health 48(2):107–119PubMedGoogle Scholar
  167. Pillarisetti S, Saxena U (2004) Role of oxidative stress and inflammation in the origin of type 2 diabetes–a paradigm shift. Expert Opin Ther Targets 8(5):401–408PubMedGoogle Scholar
  168. Pinheiro MC, Macchi BM, Vieira JL, Oikawa T, Amoras WW, Guimarães GA, Costa CA, Crespo-López ME, Herculano AM, Silveira LC, do Nascimento JL (2008) Mercury exposure and antioxidant defenses in women: a comparative study in the Amazon. Environ Res 107(1):53–59PubMedGoogle Scholar
  169. Pollack AZ, Schisterman EF, Goldman LR, Mumford SL, Perkins NJ, Bloom MS, Rudra CB, Browne RW, Wactawski-Wende J (2012) Relation of blood cadmium, lead, and mercury levels to biomarkers of lipid peroxidation in premenopausal women. Am J Epidemiol 175(7):645–652PubMedCentralPubMedGoogle Scholar
  170. Pollack AZ, Sjaarda L, Ahrens KA, Mumford SL, Browne RW, Wactawski-Wende J, Schisterman EF (2014) Association of cadmium, lead and mercury with paraoxonase 1 activity in women. PLoS ONE 9(3):e92152PubMedCentralPubMedGoogle Scholar
  171. Pollard KM, Landberg GP (2001) The in vitro proliferation of murine lymphocytes to mercuric chloride is restricted to mature T cells and is interleukin 1 dependent. Int Immunopharmacol 1(3):581–593PubMedGoogle Scholar
  172. Porras AG, Olson JS, Palmer G (1981) The reaction of reduced xanthine oxidase with oxygen. Kinetics of peroxide and superoxide formation. J Biol Chem 256(17):9006–9103PubMedGoogle Scholar
  173. Qian Y, Tiffany-Castiglioni E (2003) Lead-induced endoplasmic reticulum (ER) stress responses in the nervous system. Neurochem Res 28(1):153–162PubMedGoogle Scholar
  174. Qian Y, Falahatpisheh MH, Zheng Y, Ramos KS, Tiffany-Castiglioni E (2001) nduction of 78 kD glucose-regulated protein (GRP78) expression and redox-regulated transcription factor activity by lead and mercury in C6 rat glioma cells. Neurotox Res 3(6):581–589PubMedGoogle Scholar
  175. Queiroz ML, Pena SC, Salles TS, de Capitani EM, Saad ST (1998) Abnormal antioxidant system in erythrocytes of mercury-exposed workers. Hum Exp Toxicol 17(4):225–230PubMedGoogle Scholar
  176. Ravichandran M (2004) Interactions between mercury and dissolved organic matter—a review. Chemosphere 55(3):319–331PubMedGoogle Scholar
  177. Reaven GM (1993) Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 44:121–131PubMedGoogle Scholar
  178. Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37(12):1595–1607PubMedGoogle Scholar
  179. Ribarov S, Benov L, Benchev I, Monovich O, Markova V (1982) Hemolysis and peroxidation in heavy metal-treated erythrocytes; GSH content and activities of some protecting enzymes. Experientia 38(11):1354–1355Google Scholar
  180. Ribarov SR, Benov LC, Marcova VI, Benchev IC (1983) Hemoglobin-catalyzed lipid peroxidation in the presence of mercuric chloride. Chem Biol Interact 45(1):105–112PubMedGoogle Scholar
  181. Risher JF, Murray HE, Prince GR (2002) Organic mercury compounds: human exposure and its relevance to public health. Toxicol Ind Health 18(3):109–160PubMedGoogle Scholar
  182. Rizzetti DA, Torres JG, Escobar AG, Peçanha FM, Santos FW, Puntel RL, Alonso MJ, Briones AM, Salaices M, Vassallo DV, Wiggers GA (2013) Apocynin prevents vascular effects caused by chronic exposure to low concentrations of mercury. PLoS One 8(2):e55806PubMedCentralPubMedGoogle Scholar
  183. Rizzo M, Kotur-Stevuljevic J, Berneis K, Spinas G, Rini GB, Jelic-Ivanovic Z, Spasojevic-Kalimanovska V, Vekic J (2009) Atherogenic dyslipidemia and oxidative stress: a new look. Transl Res 153(5):217–223PubMedGoogle Scholar
  184. Roberts CK, Sindhu KK (2009) Oxidative stress and metabolic syndrome. Life Sci 84(21–22):705–712PubMedGoogle Scholar
  185. Romeo GR, Lee J, Shoelson SE (2012) Metabolic syndrome, insulin resistance, and roles of inflammation–mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 32(8):1771–1776PubMedGoogle Scholar
  186. Rossoni LV, Amaral SM, Vassallo PF, França A, Oliveira EM, Varner KJ, Mill JG, Vassallo DV (1999) Effects of mercury on the arterial blood pressure of anesthetized rats. Braz J Med Biol Res 32(8):989–997PubMedGoogle Scholar
  187. Rumbeiha WK, Fitzgerald SD, Vrable RA (1998) P3B72-Pro-inflammatory cytokine patiern in urine and serum of mice given a subnephrotoxic dose of mercuric chloride. Toxicol Lett 95:169–170Google Scholar
  188. Sage AT, Holtby-Ottenhof S, Shi Y, Damjanovic S, Sharma AM, Werstuck GH (2012) Metabolic syndrome and acute hyperglycemia are associated with endoplasmic reticulum stress in human mononuclear cells. Obesity (Silver Spring) 20(4):748–755Google Scholar
  189. Salonen JT, Seppänen K, Lakka TA, Salonen R, Kaplan GA (2000) Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland. Atherosclerosis 148(2):265–273PubMedGoogle Scholar
  190. Santos CX, Nabeebaccus AA, Shah AM, Camargo LL, Filho SV, Lopes LR (2014) Endoplasmic reticulum stress and Nox-mediated reactive oxygen species signaling in the peripheral vasculature: potential role in hypertension. Antioxid Redox Signal 20(1):121–134PubMedCentralPubMedGoogle Scholar
  191. Sarafian TA, Vartavarian L, Kane DJ, Bredesen DE, Verity MA (1994) bcl-2 Expression decreases methyl mercury-induced free-radical generation and cell killing in a neural cell line. Toxicol Lett 74(2):149–155PubMedGoogle Scholar
  192. Shanker G, Aschner JL, Syversen T, Aschner M (2004) Free radical formation in cerebral cortical astrocytes in culture induced by methylmercury. Brain Res Mol Brain Res 128(1):48–57PubMedGoogle Scholar
  193. Sharma SK, Goloubinoff P, Christen P (2008) Heavy metal ions are potent inhibitors of protein folding. Biochem Biophys Res Commun 372(2):341–345PubMedGoogle Scholar
  194. Shimojo N, Kumagai Y, Homma-Takeda S, Shinyashiki M, Takasawa N, Kushida K (1996) Isozyme selective induction of mouse pulmonary superoxide dismutase by the exposure to mercury vapor. Environ Toxicol Pharmacol 2(1):35–37PubMedGoogle Scholar
  195. Shinada M, Muto H, Okamura Y, Takizawa Y (1990) Induction of phospholipid peroxidation and its characteristics by methylmercury chloride and mercuric chloride in rat kidney. Chemosphere 21(1):57–67Google Scholar
  196. Sidorenkov O, Nilssen O, Grjibovski AM (2010) Metabolic syndrome in Russian adults: associated factors and mortality from cardiovascular diseases and all causes. BMC Public Health 10:582PubMedCentralPubMedGoogle Scholar
  197. Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82(2):291–295PubMedGoogle Scholar
  198. Sin WC, Wong MK, Sin YM (1989) Changes in tissue glutathione and mercury concentrations in rats following mercuric chloride injection through the hepatic portal vein. Bull Environ Contam Toxicol 42(6):942–948PubMedGoogle Scholar
  199. Skalnaya MG, Demidov VA (2007) Hair trace element contents in women with obesity and type 2 diabetes. J Trace Elem Med Biol 21(1):59–61PubMedGoogle Scholar
  200. Skalnaya MG, Tinkov AA, Demidov VA, Serebryansky EP, Nikonorov AA, Skalny AV (2014) Hair toxic element content in adult men and women in relation to body mass index. Biol Trace Elem Res 161(1):13–19PubMedGoogle Scholar
  201. Solomon HS, Hollenberg NK (1975) Catecholamine release: mechanism of mercury-induced vascular smooth muscle contraction. Am J Physiol 229(1):8–12PubMedGoogle Scholar
  202. Sorg O, Schilter B, Honegger P, Monnet-Tschudi F (1998) Increased vulnerability of neurones and glial cells to low concentrations of methylmercury in a prooxidant situation. Acta Neuropathol 96(6):621–627PubMedGoogle Scholar
  203. Sponder M, Fritzer-Szekeres M, Marculescu R, Mittlböck M, Uhl M, Köhler-Vallant B, Strametz-Juranek J (2014) Blood and urine levels of heavy metal pollutants in female and male patients with coronary artery disease. Vasc Health Risk Manag 10:311–317PubMedCentralPubMedGoogle Scholar
  204. Stacchiotti A, Li Volti G, Lavazza A, Rezzani R, Rodella LF (2009a) Schisandrin B stimulates a cytoprotective response in rat liver exposed to mercuric chloride. Food Chem Toxicol 47(11):2834–2840PubMedGoogle Scholar
  205. Stacchiotti A, Morandini F, Bettoni F, Schena I, Lavazza A, Grigolato PG, Apostoli P, Rezzani R, Aleo MF (2009b) Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead. Toxicology 264(3):215–224PubMedGoogle Scholar
  206. Stringari J, Nunes AK, Franco JL, Bohrer D, Garcia SC, Dafre AL, Milatovic D, Souza DO, Rocha JB, Aschner M, Farina M (2008) Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain. Toxicol Appl Pharmacol 227(1):147–154PubMedCentralPubMedGoogle Scholar
  207. Syversen T, Kaur P (2012) The toxicology of mercury and its compounds. J Trace Elem Med Biol 26(4):215–226PubMedGoogle Scholar
  208. Taher M, Orouji H, Mokhtarian D (2000) Study of the changes in serum lipids following mercury intoxification. J Res Med Sci 5(2):38–40Google Scholar
  209. Takahashi H, Nomiyama H, Nomiyama K (2000) Mercury elevates systolic blood pressure in spontaneously hypertensive rats. J Trace Elem Exp Med 13(2):227–237Google Scholar
  210. Tinkov AA, Skalnaya MG, Demidov VA, Serebryansky EP, Nikonorov AA, Skalny AV (2014) Hair mercury association with selenium, serum lipid spectrum and gamma-glutamyl transferase activity in adults. Biol Trace Elem Res 161(3):255–262PubMedGoogle Scholar
  211. Tomera JF, Harakal C (1986) Mercury- and lead-induced contraction of aortic smooth muscle in vitro. Arch Int Pharmacodyn Ther 283(2):295–302PubMedGoogle Scholar
  212. Torres AD, Rai AN, Hardiek ML (2000) Mercury intoxication and arterial hypertension: report of two patients and review of the literature. Pediatrics 105(3):E34PubMedGoogle Scholar
  213. Tunali-Akbay T, Sener G, Salvarli H, Sehirli O, Yarat A (2007) Protective effects of Ginkgo biloba extract against mercury(II)-induced cardiovascular oxidative damage in rats. Phytother Res 21(1):26–31PubMedGoogle Scholar
  214. Usuki F, Fujita E, Sasagawa N (2008) Methylmercury activates ASK1/JNK signaling pathways, leading to apoptosis due to both mitochondria- and endoplasmic reticulum (ER)-generated processes in myogenic cell lines. Neurotoxicology 29(1):22–30PubMedGoogle Scholar
  215. Usuki F, Yamashita A, Fujimura M (2011) Post-transcriptional defects of antioxidant selenoenzymes cause oxidative stress under methylmercury exposure. J Biol Chem 286(8):6641–6649PubMedCentralPubMedGoogle Scholar
  216. Usuki F, Fujimura M, Yamashita A (2013) Endoplasmic reticulum stress preconditioning attenuates methylmercury-induced cellular damage by inducing favorable stress responses. Sci Rep 3:2346PubMedCentralPubMedGoogle Scholar
  217. Valera B, Dewailly E, Poirier P (2009) Environmental mercury exposure and blood pressure among Nunavik Inuit adults. Hypertension 54(5):981–986PubMedGoogle Scholar
  218. Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208PubMedGoogle Scholar
  219. Van der Linden WE, Beers C (1974) Determination of the composition and the stability constants of complexes of mercury (II) with amino acids. Anal Chim Acta 68(1):143–154PubMedGoogle Scholar
  220. Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Järvinen H, Svegliati-Baroni G (2010) From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis 42(5):320–330PubMedGoogle Scholar
  221. Vaziri ND, Rodríguez-Iturbe B (2006) Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension. Nat Clin Pract Nephrol 2(10):582–593PubMedGoogle Scholar
  222. Villanueva MBG, Koizumi S, Jonai H (2000) Cytokine production by human peripheral blood mononuclear cells after exposure to heavy metals. J Health Sci 46(5):358–362Google Scholar
  223. Vupputuri S, Longnecker MP, Daniels JL, Guo X, Sandler DP (2005) Blood mercury level and blood pressure among US women: results from the National Health and Nutrition Examination Survey 1999–2000. Environ Res 97(2):195–200PubMedGoogle Scholar
  224. Wada O, Yamaguchi N, Ono T, Nagahashi M, Morimura T (1976) Inhibitory effect of mercury on kidney glutathione peroxidase and its prevention by selenium. Environ Res 12(1):75–80Google Scholar
  225. Wagner C, Sudati JH, Nogueira CW, Rocha JB (2010) In vivo and in vitro inhibition of mice thioredoxin reductase by methylmercury. Biometals 23(6):1171–1177PubMedGoogle Scholar
  226. Walczak-Drzewiecka A, Wyczółkowska J, Dastych J (2005) c-Jun N-terminal kinase is involved in mercuric ions-mediated interleukin-4 secretion in mast cells. Int Arch Allergy Immunol 136(2):181–190PubMedGoogle Scholar
  227. Wataha JC, Lewis JB, McCloud VV, Shaw M, Omata Y, Lockwood PE, Messer RL, Hansen JM (2008) Effect of mercury(II) on Nrf2, thioredoxin reductase-1 and thioredoxin-1 in human monocytes. Dent Mater 24(6):765–772PubMedGoogle Scholar
  228. Watanabe C, Kasanuma Y, Dejima Y, Satoh H (1999) The effect of prenatal methylmercury exposure on the GSH level and lipid peroxidation in the fetal brain and placenta of mice. The Tohoku journal of experimental medicine 187(2):121–126PubMedGoogle Scholar
  229. Wiggers GA, Peçanha FM, Briones AM, Pérez-Girón JV, Miguel M, Vassallo DV, Cachofeiro V, Alonso MJ, Salaices M (2008a) Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries. Am J Physiol Heart Circ Physiol 295(3):H1033–H1043PubMedGoogle Scholar
  230. Wiggers GA, Stefanon I, Padilha AS, Peçanha FM, Vassallo DV, Oliveira EM (2008b) Low nanomolar concentration of mercury chloride increases vascular reactivity to phenylephrine and local angiotensin production in rats. Comp Biochem Physiol C Toxicol Pharmacol 147(2):252–260PubMedGoogle Scholar
  231. Wolf MB, Baynes JW (2007) Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction. Biometals 20(1):73–81PubMedGoogle Scholar
  232. Woods JS, Ellis ME (1995) Up-regulation of glutathione synthesis in rat kidney by methyl mercury. Relationship to mercury-induced oxidative stress. Biochem Pharmacol 50(10):1719–1724PubMedGoogle Scholar
  233. Wössmann W, Kohl M, Grüning G, Bucsky P (1999) Mercury intoxication presenting with hypertension and tachycardia. Arch Dis Child 80(6):556–557PubMedGoogle Scholar
  234. Wu Z, Turner DR, Oliveira DB (2001) IL-4 gene expression up-regulated by mercury in rat mast cells: a role of oxidant stress in IL-4 transcription. Int Immunol 13(3):297–304PubMedGoogle Scholar
  235. Xia Z, Zhang YM, Ren J (2012) Endoplasmic Reticulum stress and metabolic syndrome: mechanisms and therapeutic potential. Acta Neuropharmacologica 2(1):33–44Google Scholar
  236. Yasutake A, Nakano A, Miyamoto K, Eto K (1997) Chronic effects of methylmercury in rats. I. Biochemical aspects. Tohoku J Exp Med 182(3):185–196PubMedGoogle Scholar
  237. Yin Z, Milatovic D, Aschner JL, Syversen T, Rocha JB, Souza DO, Sidoryk M, Albrecht J, Aschner M (2007) Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes. Brain Res 1131(1):1–10PubMedCentralPubMedGoogle Scholar
  238. Yonaha M, Saito M, Sagai M (1983) Stimulation of lipid peroxidation by methyl mercury in rats. Life Sci 32(13):1507–1514PubMedGoogle Scholar
  239. Yoshizawa K, Rimm EB, Morris JS, Spate VL, Hsieh CC, Spiegelman D, Stampfer MJ, Willett WC (2002) Mercury and the risk of coronary heart disease in men. N Engl J Med 347(22):1755–1760PubMedGoogle Scholar
  240. You CH, Kim BG, Kim JM, Yu SD, Kim YM, Kim RB, Hong YS (2011) Relationship between blood mercury concentration and waist-to-hip ratio in elderly Korean individuals living in coastal areas. J Prev Med Public Health 44(5):218–225PubMedCentralPubMedGoogle Scholar
  241. Youn JY, Siu KL, Lob HE, Itani H, Harrison DG, Cai H (2014) Role of vascular oxidative stress in obesity and metabolic syndrome. Diabetes 63(7):2344–2355PubMedGoogle Scholar
  242. Young CN, Cao X, Guruju MR, Pierce JP, Morgan DA, Wang G, Iadecola C, Mark AL, Davisson RL (2012) ER stress in the brain subfornical organ mediates angiotensin-dependent hypertension. J Clin Invest 122(11):3960–3964PubMedCentralPubMedGoogle Scholar
  243. Zabiński Z, Dabrowski Z, Moszczyński P, Rutowski J (2000) The activity of erythrocyte enzymes and basic indices of peripheral blood erythrocytes from workers chronically exposed to mercury vapours. Toxicol Ind Health 16(2):58–64PubMedGoogle Scholar
  244. Zahir F, Rizvi SJ, Haq SK, Khan RH (2006) Effect of methyl mercury induced free radical stress on nucleic acids and protein: implications on cognitive and motor functions. Indian J Clin Biochem 21(2):149–152PubMedCentralPubMedGoogle Scholar
  245. Zalba G, San José G, Moreno MU, Fortuño MA, Fortuño A, Beaumont FJ, Díez J (2001) Oxidative stress in arterial hypertension: role of NAD(P)H oxidase. Hypertension 38(6):1395–1399PubMedGoogle Scholar
  246. Zdolsek JM, Söder O, Hultman P (1994) Mercury induces in vivo and in vitro secretion of interleukin-1 in mice. Immunopharmacology 28(3):201–208PubMedGoogle Scholar
  247. Zefferino R, Piccaluga S, Lasalvia M, D’ Andrea G, Margaglione M, Ambrosi L (2006) Role of tumour necrosis factor alpha and interleukin 1 beta in promoter effect induced by mercury in human keratinocytes. Int J Immunopathol Pharmacol 19(4):15–20PubMedGoogle Scholar
  248. Zhang K, Kaufman RJ (2008) From endoplasmic-reticulum stress to the inflammatory response. Nature 454(7203):455–462PubMedCentralPubMedGoogle Scholar
  249. Zhang S, Liu X, Yu Y, Hong X, Christoffel KK, Wang B, Tsai HJ, Li Z, Liu X, Tang G, Xing H, Brickman WJ, Zimmerman D, Xu X, Wang X (2009) Genetic and environmental contributions to phenotypic components of metabolic syndrome: a population-based twin study. Obesity (Silver Spring) 17(8):1581–1587Google Scholar
  250. Zhang Y, Jiang X, Zhao X, Qian H, Wang S, Xing G, Wang S, Lu R (2010) Time-course effect and region-specificity of endoplasmic reticulum stress in rat brains acutely exposed by methylmercury. Wei Sheng Yan Jiu 39(3):271–274PubMedGoogle Scholar
  251. Zhang Y, Lu R, Liu W, Wu Y, Qian H, Zhao X, Wang S, Xing G, Yu F, Aschner M (2013) Hormetic effects of acute methylmercury exposure on grp78 expression in rat brain cortex. Dose Response 11(1):109–120PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Alexey A. Tinkov
    • 1
    • 2
  • Olga P. Ajsuvakova
    • 3
    • 4
  • Margarita G. Skalnaya
    • 5
  • Elizaveta V. Popova
    • 2
  • Anton I. Sinitskii
    • 6
  • Olga N. Nemereshina
    • 2
  • Evgenia R. Gatiatulina
    • 2
  • Alexandr A. Nikonorov
    • 2
  • Anatoly V. Skalny
    • 1
    • 5
    • 7
  1. 1.Laboratory of Biotechnology and Applied BioelementologyYaroslavl State UniversityYaroslavlRussia
  2. 2.Department of BiochemistryOrenburg State Medical AcademyOrenburgRussia
  3. 3.Department of ChemistryOrenburg State Agrarian UniversityOrenburgRussia
  4. 4.Department of Chemistry and Methods of Chemistry TeachingOrenburg State Pedagogical UniversityOrenburgRussia
  5. 5.Russian Society of Trace Elements in MedicineANO “Centre for Biotic Medicine”MoscowRussia
  6. 6.Department of Chemistry of the Pharmaceutical FacultySouth Ural State Medical UniversityChelyabinskRussia
  7. 7.Institute of Bioelementology (Russian Satellite Centre of Trace Element—Institute for UNESCO)Orenburg State UniversityOrenburgRussia

Personalised recommendations