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Metallothionein, essential elements and lipid peroxidation in mercury-exposed suckling rats pretreated with selenium

Abstract

Detoxification of mercury (Hg) with selenium (Se) in the early postnatal period with regard to the expression of metallothionein protein (MT), essential element status, and lipid peroxidation level in tissues has not been studied. Seven-day-old Wistar pups were orally pretreated with Se [6 μmol Na2SeO3/kg body weight (b.w.)] for 3 days and then cotreated with Hg (6 μmol HgCl2/kg b.w.) for the following 4 days. This group (Se + Hg) was compared to the groups treated with Hg, Se, or vehicle (control). Compared to the Hg-group, Se + Hg-group exhibited lower renal MT expression, reduced accumulation of Hg, Cu and Zn, and reduced excretion of Se, Hg and Zn in urine. In the liver, MT was stimulated by Se treatment in both, Se and Se + Hg-group. Hepatic and brain levels of the endogenous essential elements Cu, Fe, Mg, and Zn remained unchanged in all of the studied groups. Brain Hg levels and oxidation of lipids measured as thiobarbituric acid reactive substances were diminished in Se + Hg-group of pups compared to the Hg-group. This study suggests that Se pretreatment can help reduce Hg in the tissues of suckling rats, simultaneously preventing impairment of essential element levels in the kidneys and their excessive excretion via urine. Also, Se was shown to prevent oxidative damage of lipids in the brain, which is particularly susceptible to Hg during the early postnatal period.

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References

  • Abdulla M, Chmielnicka J (1990) New aspects on the distribution and metabolism of essential trace elements after dietary exposure to toxic metals. Biol Trace Elem Res 23:25–53

    CAS  Article  Google Scholar 

  • Agarwal R, Behari JR (2007) Effect of selenium pretreatment in chronic mercury intoxication in rats. Bull Environ Contam Toxicol 79:306–310. doi:10.1007/s00128-007-9226-3

    CAS  PubMed  Article  Google Scholar 

  • Agarwal R, Raisuddin S, Tewari S, Goel SK, Raizada RB, Behari JR (2010) Evaluation of comparative effect of pre- and posttreatment of selenium on mercury-induced oxidative stress, histological alterations, and metallothionein mRNA expression in rats. J Biochem Mol Toxicol 24:123–135. doi:10.1002/jbt.20320

    CAS  PubMed  Google Scholar 

  • Agha FE, Youness ER, Selim MMH, Ahmed HH (2014) Nephroprotective potential of selenium and taurine against mercuric chloride induced nephropathy in rats. Ren Fail 36:704–716. doi:10.3109/0886022X.2014.890012

    CAS  PubMed  Article  Google Scholar 

  • ATSDR (1999) Toxicological profile for mercury. U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta. http://www.atsdr.cdc.gov/ToxProfiles/tp46.pdf. Accessed 15 Nov 2014

  • Bogden JD, Kemp FW, Troiano RA, Jortner BS, Timpone C, Giuliani D (1980) Effect of mercuric chloride and methylmercury chloride exposure on tissue concentrations of six essential minerals. Environ Res 21:350–359

    CAS  PubMed  Article  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    CAS  PubMed  Article  Google Scholar 

  • Brambila E, Liu J, Morgan DL, Beliles RP, Waalkes MP (2002) Effect of mercury vapor exposure on metallothionein and glutathione S-transferase gene expression in the kidney of nonpregnant, pregnant, and neonatal rats. J Toxicol Environ Health A 65:1273–1288. doi:10.1080/00984100290071405

    CAS  PubMed  Article  Google Scholar 

  • Brandão R, Borges LP, Nogueira CW (2009) Concomitant administration of sodium 2,3-dimercapto-1-propanesulphonate (DMPS) and diphenyl diselenide reduces effectiveness of DMPS in restoring damage induced by mercuric chloride in mice. Food Chem Toxicol 47:1771–1778. doi:10.1016/j.fct.2009.04.035

    PubMed  Article  Google Scholar 

  • Bridges CC, Zalups RK (2010) Transport of inorganic mercury and methylmercury in target tissues and organs. J Toxicol Environ Health B 13:385–410. doi:10.1080/10937401003673750

    CAS  Article  Google Scholar 

  • Cherian MG, Templeton DM, Gallant KR, Banerjee D (1987) Biosynthesis and metabolism of metallothionein in rat during perinatal development. Exp Suppl 52:499–505

    CAS  Article  Google Scholar 

  • Chmielnicka J, Brzeźnicka E, Sniady A (1986) Kidney concentrations and urinary excretion of mercury, zinc and copper following the administration of mercuric chloride and sodium selenite to rats. Arch Toxicol 59:16–20

    CAS  PubMed  Article  Google Scholar 

  • Chowdhury BA, Chandra RK (1987) Biological and health implications of toxic heavy metal and essential trace element interactions. Prog Food Nutr Sci 11:55–113

    CAS  PubMed  Google Scholar 

  • Clarkson TW (1997) The toxicology of mercury. Crit Rev Clin Lab Sci 34:369–403

    CAS  PubMed  Article  Google Scholar 

  • Clarkson TW, Magos L (2006) The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 36:609–662

    CAS  PubMed  Article  Google Scholar 

  • Ercal N, Gure-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress Part I: mechanisms involved in metal induced oxidative damage. Curr Top Med Chem 1:529–539

    CAS  PubMed  Article  Google Scholar 

  • Falnoga I, Tušek-Žnidarič M (2007) Selenium–mercury interactions in man and animals. Biol Trace Elem Res 119:212–220. doi:10.1007/s12011-007-8009-3

    CAS  PubMed  Article  Google Scholar 

  • Farina M, Brandão R, de Lara FS, Pagliosa LB, Soares FA, Souza DO, Rocha JB (2003) Profile of nonprotein thiols, lipid peroxidation and delta-aminolevulinate dehydratase activity in mouse kidney and liver in response to acute exposure to mercuric chloride and sodium selenite. Toxicology 184:179–187

    CAS  PubMed  Article  Google Scholar 

  • Feng W, Wang M, Li B, Liu J, Chai Z, Zhao J, Deng G (2004) Mercury and trace element distribution in organic tissues and regional brain of fetal rat after in utero and weaning exposure to low dose of inorganic mercury. Toxicol Lett 152:223–234. doi:10.1016/j.toxlet.2004.05.001

    CAS  PubMed  Article  Google Scholar 

  • Fernandez EL, Dencker L, Tallkvist J (2007) Expression of ZnT-1 (Slc30a1) and MT-1 (Mt1) in the conceptus of cadmium treated mice. Reprod Toxicol 24:353–358. doi:10.1016/j.reprotox.2007.06.006

    CAS  PubMed  Article  Google Scholar 

  • Grandjean P et al (2008) The Faroes statement: human health effects of developmental exposure to chemicals in our environment. Basic Clin Pharmacol Toxicol 102:73–75. doi:10.1111/j.1742-7843.2007.00114.x

    CAS  PubMed  Google Scholar 

  • Haase H, Maret W (2008) Partial oxidation and oxidative polymerization of metallothionein. Electrophoresis 29:4165–4176

    Article  Google Scholar 

  • Iwai N, Watanabe C, Suzuki T, Suzuki KT, Tohyama C (1988) Metallothionein induction by sodium selenite at two different ambient temperatures in mice. Arch Toxicol 62:447–451

    CAS  PubMed  Article  Google Scholar 

  • Khan MA, Wang F (2009) Mercury–selenium compounds and their toxicological significance: toward a molecular understanding of the mercury–selenium antagonism. Environ Toxicol Chem 28:1567–1577. doi:10.1897/08-375.1

    CAS  PubMed  Article  Google Scholar 

  • Kostial K, Šimonović I, Pišonić M (1971) Lead absorption from the intestine in newborn rats. Nature 233:564

    CAS  PubMed  Article  Google Scholar 

  • Kostial K, Kello D, Jugo S, Rabar I, Maljković T (1978) Influence of age on metal metabolism and toxicity. Environ Health Perspect 25:81–86

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Liu X, Jin T, Nordberg GF (1991) Increased urinary calcium and magnesium excretion in rats injected with mercuric chloride. Pharmacol Toxicol 68:254–259

    CAS  PubMed  Article  Google Scholar 

  • Liu X, Nordberg GF, Jin T (1992) Increased urinary excretion of zinc and copper by mercuric chloride injection in rats. Biometals 5:17–22

    CAS  PubMed  Article  Google Scholar 

  • Luque-Garcia JL, Cabezas-Sanchez P, Anunciação DS, Camara C (2013) Analytical and bioanalytical approaches to unravel the selenium–mercury antagonism: a review. Anal Chim Acta 801:1–13. doi:10.1016/j.aca.2013.08.043

    CAS  PubMed  Article  Google Scholar 

  • Magos L, Webb M (1976) Differences in distribution and excretion of selenium and cadmium or mercury after their simultaneous administration subcutaneously in equimolar doses. Arch Toxicol 36:63–69

    CAS  PubMed  Article  Google Scholar 

  • Maret W (2000) The function of zinc metallothionein: a link between cellular zinc and redox state. J Nutr 130(5S Suppl):1455S–1458S

    CAS  PubMed  Google Scholar 

  • Mehra RK, Bremner I (1984) Metallothionein-I in the plasma and liver of neonatal rats. Biochem J 217:859–862

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miller RK (1983) Perinatal toxicology: its recognition and fundamentals. Am J Ind Med 4:205–244

    CAS  PubMed  Article  Google Scholar 

  • Mizzen CA, Cartel NJ, Yu WH, Fraser PE, McLachlan DR (1996) Sensitive detection of metallothioneins-1, -2 and -3 in tissue homogenates by immunoblotting: a method for enhanced membrane transfer and retention. J Biochem Biophys Methods 32:77–83

    CAS  PubMed  Article  Google Scholar 

  • Nielsen JB, Andersen O (1991) A comparison of the effects of sodium selenite and seleno-l-methionine on disposition of orally administered mercuric chloride. J Trace Elem Electrolytes Health Dis 5:245–250

    CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    CAS  PubMed  Article  Google Scholar 

  • Orct T, Lazarus M, Jurasović J, Blanuša M, Piasek M, Kostial K (2009) Influence of selenium dose on mercury distribution and retention in suckling rats. J Appl Toxicol 29:585–589. doi:10.1002/jat.1444

    CAS  PubMed  Article  Google Scholar 

  • Peixoto NC, Serafim MA, Flores EMM, Bebianno MJ, Pereira ME (2007) Metallothionein, zinc, and mercury levels in tissues of young rats exposed to zinc and subsequently to mercury. Life Sci 81:1264–1271. doi:10.1016/j.lfs.2007.08.038

    CAS  PubMed  Article  Google Scholar 

  • Peixoto NC, Rocha LC, Moraes DP, Bebianno MJ, Dressler VL, Flores EM, Pereira ME (2008) Changes in levels of essential elements in suckling rats exposed to zinc and mercury. Chemosphere 72:1327–1332. doi:10.1016/j.chemosphere.2008.04.027

    CAS  PubMed  Article  Google Scholar 

  • Peraza MA, Ayala-Fierro F, Barber DS, Casarez E, Rael LT (1998) Effects of micronutrients on metal toxicity. Environ Health Perspect 106(Suppl 1):203–216

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Perottoni J, Lobato LP, Silveira A, Rocha JB, Emanuelli T (2004a) Effects of mercury and selenite on delta-aminolevulinate dehydratase activity and on selected oxidative stress parameters in rats. Environ Res 95:166–173. doi:10.1016/j.envres.2003.08.007

    CAS  PubMed  Article  Google Scholar 

  • Perottoni J, Rodrigues OE, Paixão MW, Zeni G, Lobato LP, Braga AL, Rocha JB, Emanuelli T (2004b) Renal and hepatic ALA-D activity and selected oxidative stress parameters of rats exposed to inorganic mercury and organoselenium compounds. Food Chem Toxicol 42:17–28. doi:10.1016/j.fct.2003.08.002

    CAS  PubMed  Article  Google Scholar 

  • Ralston NV, Raymond LJ (2010) Dietary selenium’s protective effects against methylmercury toxicity. Toxicology 278:112–123. doi:10.1016/j.tox.2010.06.004

    CAS  PubMed  Article  Google Scholar 

  • Romero A, Ramos E, de Los Ríos C, Egea J, Del Pino J, Reiter RJ (2014) A review of metal-catalyzed molecular damage: protection by melatonin. J Pineal Res 56:343–370. doi:10.1111/jpi.12132

    CAS  PubMed  Article  Google Scholar 

  • Rooney JP (2007) The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury. Toxicology 234:145–156. doi:10.1016/j.tox.2007.02.016

    CAS  PubMed  Article  Google Scholar 

  • Sabolić I, Breljak D, Škarica M, Herak-Kramberger CM (2010) Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals 23:897–926. doi:10.1007/s10534-010-9351-z

    PubMed  Article  Google Scholar 

  • Su L, Wang M, Yin ST, Wang HL, Chen L, Sun LG, Ruan DY (2008) The interaction of selenium and mercury in the accumulations and oxidative stress of rat tissues. Ecotoxicol Environ Saf 70:483–489. doi:10.1016/j.ecoenv.2007.05.018

    CAS  PubMed  Article  Google Scholar 

  • Telišman S (1995) Interactions of essential and/or toxic metals and metalloid regarding interindividual differences in susceptibility to various toxicants and chronic diseases in man. Arh Hig Rada Toksikol 46:459–476

    PubMed  Google Scholar 

  • U.S. Environmental Protection Agency, EPA (2002) Child-specific exposure factors handbook. EPA/600/P-00/002B. National Center for Environmental Assessment, Washington, DC. http://www.epa.gov/ncea. Accessed 10 Dec 2014

  • U.S. Environmental Protection Agency, EPA (2007) Inorganic mercury. Toxicity and exposure assessment for children’s health (TEACH) chemical summary. http://www.epa.gov/teach/chem_summ/mercury_inorg_summary.pdf. Accessed 15 Nov 2014

  • Watanabe C (2002) Modification of mercury toxicity by selenium: practical importance? Tohoku J Exp Med 196:71–77

    CAS  PubMed  Article  Google Scholar 

  • WHO (1986) Environmental Health Criteria 59: principles for evaluating health risks from chemicals during infancy and childhood: the need for a special approach. World Health Organization, Geneva

    Google Scholar 

  • Yang D-Y, Chen Y-W, Gunn JM, Belzile N (2008) Selenium and mercury in organisms: interactions and mechanisms. Environ Rev 16:71–92. doi:10.1139/A08-001

    CAS  Article  Google Scholar 

  • Zalups RK (2000) Molecular interactions with mercury in the kidney. Pharmacol Rev 52:113–144

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Ministry of Science Education and Sports of the Republic of Croatia (Project Grants No. 022-0222148-2135 and 022-0222148-2146). The technical assistance of Mrs. Đurđa Breški, Marija Ciganović and Snježana Mataušić is gratefully acknowledged. The authors thank Mr. Makso Herman for language advice.

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Correspondence to Maja Lazarus.

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Orct, T., Lazarus, M., Ljubojević, M. et al. Metallothionein, essential elements and lipid peroxidation in mercury-exposed suckling rats pretreated with selenium. Biometals 28, 701–712 (2015). https://doi.org/10.1007/s10534-015-9859-3

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  • DOI: https://doi.org/10.1007/s10534-015-9859-3

Keywords

  • Selenium supplementation
  • Mercury exposure
  • Suckling rat
  • Metallothionein
  • Essential element
  • Lipid peroxidation