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Biological Trace Element Research

, Volume 184, Issue 2, pp 409–421 | Cite as

Early-Life Exposure to Cadmium Triggers Distinct Zn-Dependent Protein Expression Patterns and Impairs Brain Development

  • Safa Ben Mimouna
  • Marouane Chemek
  • Sana Boughammoura
  • Mohamed Banni
  • Imed Messaoudi
Article

Abstract

The objective of this study was to determine if the brain development impairment induced by early-life exposure to cadmium (Cd) could result from changes in the expression pattern of distinct zinc (Zn)-dependent proteins. For this purpose, adult female rats receiving either tap water, Cd, Zn, or Cd + Zn in their drinking water during gestation and lactation periods were used. After birth, the male offspring were screened for locomotors and sensorial defects. At postnatal day 21 (PND 21), the male pups were sacrificed and their brains, liver, and plasma were taken for chemical, biochemical, and molecular analyses. Our results show that exposure to Cd significantly increased the metal accumulation and decreased Zn concentrations in the brain of male pups from Cd-treated mothers. Besides, Cd exposure reduced significantly the locomotor activity of the offspring in open-field test, the body weight, and the cranio-caudal length at PND21. Insulin-like growth factor-I (IGF-1) levels in the plasma and liver were also decreased in male pups from Cd-treated mothers. Cd-induced brain development disruption was accompanied by a significant increase of the superoxide dismutase (SOD) activity, induction of the metallothionein (MT) synthesis, and, at the molecular level, by an upregulation of Zrt-,Irt-related protein 6 (ZIP6) gene and a significant downregulation of the expression of the Zn transporter 3 (ZnT3) and brain-derived neurotrophic factor (BDNF) genes in the brain. No significant changes on the expression of genes encoding other Zn-dependent proteins and factors such as ZnT1, ZIP12, NF-κB, and Zif268. Interestingly, Zn supplementation provided a total or partial correction of the changes induced by the Cd exposure. These data indicated that changes in expression of ZnT3 and ZIP6 as well as alteration of other transcription factors, such as BDNF, or Zn-dependent proteins, such as SOD and MTs, in response to Cd exposure might be an underlying mechanism of Cd-induced brain development impairment.

Keywords

Brain development Cadmium Rat Zinc Zn-dependent proteins 

Notes

Acknowledgements

This research was supported by the Ministry of Higher Education, Scientific Research and Technology of Tunisia.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there are no conflicts of interest.

References

  1. 1.
    Lane TW, Saito MA, George GN, Pickering IJ, Prince RC, Morel FM (2005) Biochemistry: a cadmium enzyme from a marine diatom. Nature 435(7038):42–52.  https://doi.org/10.1038/435042a CrossRefPubMedGoogle Scholar
  2. 2.
    Lane TW, Morel FM (2000) A biological function for cadmium in marine diatoms. Proc Natl Acad Sci U S A 97(9):4627–4631.  https://doi.org/10.1073/pnas.090091397 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ebert-McNeill A, Clark S, Miller J, Birdsall P, Chandar M, Wu L, Cerny A, Hall P, Johnson M, Isales C, Chutkan N, Bhattacharyya N (2012) Cadmium intake and systemic exposure in postmenopausal women and age-matched men who smoke cigarettes. Toxicol Sci 130(1):191–204.  https://doi.org/10.1093/toxsci/kfs226 CrossRefPubMedGoogle Scholar
  4. 4.
    Alessandria I, Pennisi M, Cataudella E, Frazzetto PM, Mala-guarnera M, Rampello L (2012) Neurotoxicity in cadmium-exposed workers. Acta Medica Med 28:253Google Scholar
  5. 5.
    Terçariol SG, Almeida AA, Godinho AF (2011) Cadmium and exposure to stress increase aggressive behavior. Environ Toxicol Pharmacol 32(1):40–45.  https://doi.org/10.1016/j.etap.2011.03.005 CrossRefPubMedGoogle Scholar
  6. 6.
    Mendez-Armenta M, Barroso-Moguel R, Villeda-Hernández J, Nava-Ruı́z C, Rı́os C (2001) Histopathological alterations in the brain regions of rats after perinatal combined treatment with cadmium and dexamethasone. Toxicology 161(3):189–199.  https://doi.org/10.1016/S0300-483X(01)00349-3 CrossRefPubMedGoogle Scholar
  7. 7.
    Lafuente JV, Adan B, Cervos-Navarro J (2000) Effects of chronic deep hypoxia on the expression of nitric oxide synthase in the rat brain. Acta Neurochir Suppl 76:111–113PubMedGoogle Scholar
  8. 8.
    Basha MR, raddy NS, Zawia NH, Kodavanti PR (2006) Ontogenetic alterations in prototypical transcription factors in the rat cerebellum and hippocampus following perinatal exposure to a commercial PCB mixture. Neurotoxicology 27(1):118–124.  https://doi.org/10.1016/j.neuro.2005.07.006 CrossRefPubMedGoogle Scholar
  9. 9.
    Desi I, Nagymajtenyi L, Schulz H (1998) Behavioural and neurotoxicological changes caused by cadmium treatment of rats during development. J Appl Toxicol 18(1):63–70CrossRefPubMedGoogle Scholar
  10. 10.
    Salvatori F, Talassi CB, Salzgeber SA, Spinosa HS, Bernardi MM (2004) Embryotoxic and long-term effects of cadmium exposure during embryogenesis in rats. Neurotoxicol Teratol 26(5):673–680.  https://doi.org/10.1016/j.ntt.2004.05.001 CrossRefPubMedGoogle Scholar
  11. 11.
    Brzoska MM, Moniuszko-Jakoniuk J (2001) Interactions between cadmium and zinc in the organism. Food Chem Toxicol 39(10):967–980.  https://doi.org/10.1016/S0278-6915(01)00048-5 CrossRefPubMedGoogle Scholar
  12. 12.
    Chouchene L, Banni M, Kerkeni A, Saïd K, Messaoudi I (2011) Cadmium-induced ovarian pathophysiology is mediated by change in gene expression pattern of zinc transporters in zebrafish (Danio rerio). Chem Biol Interact 193(2):172–179.  https://doi.org/10.1016/j.cbi.2011.06.010 CrossRefPubMedGoogle Scholar
  13. 13.
    Boughammoura S, Chemek M, Mimouna SB, Banni M, Messaoudi I (2017) Involvement of Zn depletion in Cd-induced toxicity on prenatal bone formation in rat. Biol Trace Elem Res in press 180(1):70–80.  https://doi.org/10.1007/s12011-017-0981-7 CrossRefPubMedGoogle Scholar
  14. 14.
    Eide DJ (2004) The SLC39 family of metal ion transporters. Pflugers Arch 447(5):796–800.  https://doi.org/10.1007/s00424-003-1074-3 CrossRefPubMedGoogle Scholar
  15. 15.
    Bridges CC, Zalups RK (2005) Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol 204(3):274–308.  https://doi.org/10.1016/j.taap.2004.09.007 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Dalton TP, He L, Wang B, Miller ML, Jin L, Stringer KF, Chang X, Baxter CS, Nebert DW (2005) Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis. Proc Natl Acad Sci U S A 102(9):3401–3406.  https://doi.org/10.1073/pnas.0406085102 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Chemek M, Boughammoura S, Ben Mimouna S, Chouchene L, Banni M, Messaoudi I (2015) Changes of the mRNA expression pattern of Zn transporters: a probable mechanism for cadmium retention and zinc redistribution in the suckling rat tissues. Biol Trace Elem Res 165(2):173–182.  https://doi.org/10.1007/s12011-015-0255-1 CrossRefPubMedGoogle Scholar
  18. 18.
    Chemek M, Ben Mimouna S, Boughammoura S, Delbès G, Messaoudi I (2016) Protective role of zinc against the toxicity induced by exposure to cadmium during gestation and lactation on testis development. Reprod Toxicol 63:151–160.  https://doi.org/10.1016/j.reprotox.2016.06.005 CrossRefPubMedGoogle Scholar
  19. 19.
    Chemek, M, Venditti M, Boughamoura S, Mimouna SB, Messaoudi I, Minucci S (2017) Involvement of testicular DAAM1 expression in zinc protection against cadmium-induced male rat reproductive toxicity. J Cell PhysiolGoogle Scholar
  20. 20.
    Barański B (1986) Effect of maternal cadmium exposure on postnatal development and tissue cadmium, copper and zinc concentrations in rats. Arch Toxicol 58(4):255–260.  https://doi.org/10.1007/BF00297116 CrossRefPubMedGoogle Scholar
  21. 21.
    Brzoska MM, Rogalska J, Galazyn-Sidorczuk M, Jurczuk M, Roszczenko A, Kulikowska-Karpińska E, Moniuszko-Jakoniuk J (2007) Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium. Toxicology 237(1–3):89–103.  https://doi.org/10.1016/j.tox.2007.05.001 CrossRefPubMedGoogle Scholar
  22. 22.
    Altman J, Sudarshan K (1975) Postnatal development of locomotion in the laboratory rat. Anim Behav 23(4):896–920.  https://doi.org/10.1016/0003-3472(75)90114-1 CrossRefPubMedGoogle Scholar
  23. 23.
    Fox NC, Warrington EK, Freeborough PA, Hartikainen P, Kennedy AM, Stevens JM, Rossor MN (1996) Presymptomatic hippocampal atrophy in Alzheimer’s disease. A longitudinal MRI study. Brain 119(6):2001–2007.  https://doi.org/10.1093/brain/119.6.2001 CrossRefPubMedGoogle Scholar
  24. 24.
    Viarengo A, Ponzano E, Dondero F, Fabbri R (1997) A simple spectrophotometric method for metallothionein evaluation in marine organisms: an application to Mediterranean and Antarctic molluscs. Mar Environ Res 44(1):69–84.  https://doi.org/10.1016/S0141-1136(96)00103-1 CrossRefGoogle Scholar
  25. 25.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of dye binding. Analyt Biochemist 72(1-2):248–254.  https://doi.org/10.1016/0003-2697(76)90527-3 CrossRefGoogle Scholar
  26. 26.
    Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47(3):469–474.  https://doi.org/10.1111/j.1432-1033.1974.tb03714.x CrossRefPubMedGoogle Scholar
  27. 27.
    Banni M, Negri A, Mignone F, Boussetta H, Viarengo A, Dondero F (2011) Gene expression rhythms in the mussel Mytilus galloprovincialis (Lam.) across an annual cycle. PLoS One 6(5):e18904.  https://doi.org/10.1371/journal.pone.0018904 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res:30–36Google Scholar
  29. 29.
    Pari L, Murugavel P (2007) Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicology 234(1-2):44–50.  https://doi.org/10.1016/j.tox.2007.01.021 CrossRefPubMedGoogle Scholar
  30. 30.
    Chouchene L, Pellegrini E, Gueguen MM, Hinfray N, Brion F, Piccini B, Messaouid I, Pakdel F (2016) Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc. J Appl Toxicol JAT 36(6):863–871.  https://doi.org/10.1002/jat.3285 CrossRefPubMedGoogle Scholar
  31. 31.
    Messaoudi I, Banni M, Saïd L, Saïd K, Kerkeni A (2010) Evaluation of involvement of testicular metallothionein gene expression in the protective effect of zinc against cadmium-induced testicular pathophysiology in rat. Reprod Toxicol 29(3):339–345.  https://doi.org/10.1016/j.reprotox.2010.01.004 CrossRefPubMedGoogle Scholar
  32. 32.
    Petersson Grawe K, Teiling-Gårdlund A, Jalkesten E, Oskarsson A (2004) Increased spontaneous motor activity in offspring after maternal cadmium exposure during lactation. Environ Toxicol Pharmacol 17(1):35–43.  https://doi.org/10.1016/j.etap.2004.02.001 CrossRefPubMedGoogle Scholar
  33. 33.
    Whelton BD, Toomey JM, Bhattacharyya MH (1993) Cadmium-109 metabolism in mice. IV. Diet versus maternal stores as a source of cadmium transfer to mouse fetuses and pups during gestation and lactation. J Toxicol Environ Health 40(4):531–546.  https://doi.org/10.1080/15287399309531817 CrossRefPubMedGoogle Scholar
  34. 34.
    Hart RP, Rose CS, Hamer RM (1989) Neuropsychological effects of occupational exposure to cadmium. J Clin Exp Neuropsychol 11(6):933–943.  https://doi.org/10.1080/01688638908400946 CrossRefPubMedGoogle Scholar
  35. 35.
    Viaene MK, Masschelein R, Leenders J, De Groof M, Swerts LJ, Roels HA (2000) Neurobehavioural effects of occupational exposure to cadmium: a cross sectional epidemiological study. Occup Environ Med 57(1):19–27.  https://doi.org/10.1136/oem.57.1.19 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Baranski B (1984) Behavioral alterations in offspring of female rats repeatedly exposed to cadmium oxide by inhalation. Toxicol Lett 22(1):53–61.  https://doi.org/10.1016/0378-4274(84)90045-6 CrossRefPubMedGoogle Scholar
  37. 37.
    Goncalves JF, Fiorenza AM, Spanevello RM, Mazzanti CM, Bochi GV, Antes FG, Stefanello N, Rubin MA, Dressler VL, Morsch VM, Schetinger MR (2010) N-acetylcysteine prevents memory deficits, the decrease in acetylcholinesterase activity and oxidative stress in rats exposed to cadmium. Chem Biol Interact 186(1):53–60.  https://doi.org/10.1016/j.cbi.2010.04.011 CrossRefPubMedGoogle Scholar
  38. 38.
    Ciesielski T, Weuve J, Bellinger DC, Schwartz J, Lanphear B, Wright RO (2012) Cadmium exposure and neurodevelopmental outcomes in U.S. children. Environ Health Perspect 120(5):758–763.  https://doi.org/10.1289/ehp.1104152 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Smith MJ, Pihl RO, Garber B (1982) Postnatal cadmium exposure and long term behavioral changes in the rat. Neurobehav Toxicol Teratol 4(3):283–287PubMedGoogle Scholar
  40. 40.
    Ishitobi H, Mori K, Yoshida K, Watanabe C (2007) Effects of perinatal exposure to low-dose cadmium on thyroid hormone-related and sex hormone receptor gene expressions in brain of offspring. Neurotoxicology 28(4):790–797.  https://doi.org/10.1016/j.neuro.2007.02.007 CrossRefPubMedGoogle Scholar
  41. 41.
    Nagymajtenyi L, Schulz H, Desi I (1997) Behavioural and functional neurotoxicological changes caused by cadmium in a three-generational study in rats. Hum Exp Toxicol 16(12):691–699.  https://doi.org/10.1177/096032719701601201 CrossRefPubMedGoogle Scholar
  42. 42.
    Martin P, Pognonec P (2010) ERK and cell death: cadmium toxicity, sustained ERK activation and cell death. FEBS J 277(1):39–46.  https://doi.org/10.1111/j.1742-4658.2009.07369.x CrossRefPubMedGoogle Scholar
  43. 43.
    O'Kusky J, Ye P (2012) Neurodevelopmental effects of insulin-like growth factor signaling. Front Neuroendocrinol 33(3):230–251.  https://doi.org/10.1016/j.yfrne.2012.06.002 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Turgut S, Kaptanoglu B, Turgut G, Emmungil G, Genç O (2005) Effects of cadmium and zinc on plasma levels of growth hormone, insulin-like growth factor I, and insulin-like growth factor-binding protein 3. Biol Trace Elem Res 108(1-3):197–204.  https://doi.org/10.1385/BTER:108:1-3:197 CrossRefPubMedGoogle Scholar
  45. 45.
    Luo ZC, Delvin E, Fraser WD (2010) Maternal glucose tolerance in pregnancy affects fetal insulin sensitivity. Diabet Care 33(9):2055–2061.  https://doi.org/10.2337/dc10-0819 CrossRefGoogle Scholar
  46. 46.
    Hanna LA, Clegg MS, Ellis-Hutchings RG, Niles BJ, Keen CL (2010) The influence of gestational zinc deficiency on the fetal insulin-like growth factor axis in the rat. Exp Biol Med (Maywood) 235(2):206–214.  https://doi.org/10.1258/ebm.2009.009018 CrossRefGoogle Scholar
  47. 47.
    Tran CD, Butler RN, Howarth GS, Philcox JC, Rofe AM, Coyle P (1999) Regional distribution and localization of zinc and metallothionein in the intestine of rats fed diets differing in zinc content. Scand J Gastroenterol 34(7):689–695CrossRefPubMedGoogle Scholar
  48. 48.
    Sato M, Bremner I (1992) Oxygen free radicals and metallothionein. Free Radic Biol Med 14(3):325–337CrossRefGoogle Scholar
  49. 49.
    Gasull T, Giralt M, Hernandez J, Martinez P, Bremner I, Hidalgo J (1994) Regulation of metallothionein concentrations in rat brain: effect of glucocorticoids, zinc, copper and endotoxin. Am J Phys 266:760–767Google Scholar
  50. 50.
    Bauer R, Demeter I, Hasemann V, Johansen JT (1980) Structural properties of the zinc site in Cu,Zn-superoxide dismutase; perturbed angular correlation of gamma ray spectroscopy on the Cu, 111Cd-superoxide dismutase derivative. Biochem Biophys Res Commun 94(4):1296–1302.  https://doi.org/10.1016/0006-291X(80)90560-4 CrossRefPubMedGoogle Scholar
  51. 51.
    Palmiter RD (2004) Protection against zinc toxicity by metallothionein and zinc transporter 1. Proc Natl Acad Sci U S A 101(14):4918–4923.  https://doi.org/10.1073/pnas.0401022101 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Ohana E, Hoch E, Keasar C, Kambe T, Yifrach O, Hershfinkel M, Sekler I (2009) Identification of the Zn2+ binding site and mode of operation of a mammalian Zn2+ transporter. J Biol Chem 284(26):17677–17686.  https://doi.org/10.1074/jbc.M109.007203 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Dufner-Beattie J, Langmade SJ, Wang F, Eide D, Andrews GK (2003) Structure, function, and regulation of a subfamily of mouse zinc transporter genes. J Biol Chem 278(50):50142–50150.  https://doi.org/10.1074/jbc.M304163200 CrossRefPubMedGoogle Scholar
  54. 54.
    Buxani-Rice S, Ueda F, Bradbury MW (1994) Transport of zinc-65 at the blood-brain barrier during short cerebrovascular perfusion in the rat: its enhancement by histidine. J Neurochem 62(2):665–672CrossRefPubMedGoogle Scholar
  55. 55.
    Ebendal T (1992) Function and evolution in the NGF family and its receptors. J Neurosci Res 32(4):461–470.  https://doi.org/10.1002/jnr.490320402 CrossRefPubMedGoogle Scholar
  56. 56.
    Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350(6315):230–232.  https://doi.org/10.1038/350230a0 CrossRefPubMedGoogle Scholar
  57. 57.
    Zhou J, Bradford HF, Stern GM (1994) The stimulatory effect of brain-derived neurotrophic factor on dopaminergic phenotype expression of embryonic rat cortical neurons in vitro. Brain Res Dev Brain Res 81:18–24CrossRefGoogle Scholar
  58. 58.
    Schmidt RH, Nickerson JM, Boatright JH (2016) Exercise as gene therapy: BDNF and DNA damage repair. Asia Pac J Ophthalmol (Phila) 5(4):309–311.  https://doi.org/10.1097/APO.0000000000000226 CrossRefGoogle Scholar
  59. 59.
    Kubo T, Nonomura T, Enokido Y, Hatanaka H (1995) Brain-derived neurotrophic factor (BDNF) can prevent apoptosis of rat cerebellar granule neurons in culture. Brain Res Dev Brain Res 85(2):249–258.  https://doi.org/10.1016/0165-3806(94)00220-T CrossRefPubMedGoogle Scholar
  60. 60.
    Nagappan G, Zaitsev E, Senatorov VV Jr, Yang J, Hempstead BL, Lu B (2009) Control of extracellular cleavage of ProBDNF by high frequency neuronal activity. Proc Natl Acad Sci U S A 106(4):1267–1272.  https://doi.org/10.1073/pnas.0807322106 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Yang XX, Zhu AN, Li FX, Zhang ZX, Li M (2013) Neurogenic locus notch homolog protein 4 and brain-derived neurotrophic factor variants combined effect on schizophrenia susceptibility. Acta Neuropsychiatr 25(06):356–360.  https://doi.org/10.1017/neu.2013.13 CrossRefPubMedGoogle Scholar
  62. 62.
    Hwang JJ, Park MH, Choi SY, Koh JY (2005) Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases. J Biol Chem 280(12):11995–12001.  https://doi.org/10.1074/jbc.M403172200 CrossRefPubMedGoogle Scholar
  63. 63.
    ZQ X, Sun Y, Li HY, Lim Y, Zhong JH, Zhou XF (2011) Endogenous proBDNF is a negative regulator of migration of cerebellar granule cells in neonatal mice. Eur J Neurosci 33:1376–1384CrossRefGoogle Scholar
  64. 64.
    Mackenzie GG, Keen CL, Oteiza PI (2006) Microtubules are required for NF-kappaB nuclear translocation in neuroblastoma IMR-32 cells: modulation by zinc. J Neurochem 99(2):402–415.  https://doi.org/10.1111/j.1471-4159.2006.04005.x CrossRefPubMedGoogle Scholar
  65. 65.
    Adamo AM, Zago MP, Mackenzie GG, Aimo L, Keen CL, Keenan A, Oteiza PI (2010) The role of zinc in the modulation of neuronal proliferation and apoptosis. Neurotox Res 17(1):1–14.  https://doi.org/10.1007/s12640-009-9067-4 CrossRefPubMedGoogle Scholar
  66. 66.
    Knapska E, Kaczmarek L (2004) A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK? Prog Neurobiol 74(4):183–211.  https://doi.org/10.1016/j.pneurobio.2004.05.007 CrossRefPubMedGoogle Scholar
  67. 67.
    Veyrac A, Besnard A, Caboche J, Davis S, Laroche S (2014) The transcription factor Zif268/Egr1, brain plasticity, and memory. Prog Mol Biol Transl Sci 122:89–129.  https://doi.org/10.1016/B978-0-12-420170-5.00004-0 CrossRefPubMedGoogle Scholar
  68. 68.
    Zawia NH, Sharan R, Brydie M, Oyama T, Crumpton T (1998) Sp1 as a target site for metal-induced perturbations of transcriptional regulation of developmental brain gene expression. Brain Res Dev Brain Res 107(2):291–298.  https://doi.org/10.1016/S0165-3806(98)00023-6 CrossRefPubMedGoogle Scholar
  69. 69.
    Eom KS, Cheong JS, Lee SJ (2016) Structural analyses of zinc finger domains for specific interactions with DNA. J Microbiol Biotechnol 28:2019–2029CrossRefGoogle Scholar
  70. 70.
    Goldenberg RL, Tamura T, Neggers Y, Copper RL, Johnston KE, DuBard MB, Hauth JC (1995) The effect of zinc supplementation on pregnancy outcome. JAMA 274(6):463–468.  https://doi.org/10.1001/jama.1995.03530060037030 CrossRefPubMedGoogle Scholar
  71. 71.
    Chowanadisai W, Kelleher SL, Lonnerdal B (2005) Maternal zinc deficiency reduces NMDA receptor expression in neonatal rat brain, which persists into early adulthood. J Neurochem 94(2):510–519.  https://doi.org/10.1111/j.1471-4159.2005.03246.x CrossRefPubMedGoogle Scholar
  72. 72.
    Carageorgiou H, Tzotzes V, Sideris A, Tsakiris A (2005) Cadmium effects on brain acetylcholinesterase activity and antioxidant status of adult rats: modulation by zinc, calcium and L-cysteine co-administration. Basic Clin Pharmacol Toxicol 97(5):320–324.  https://doi.org/10.1111/j.1742-7843.2005.pto_174.x CrossRefPubMedGoogle Scholar
  73. 73.
    Braga MM, Dick T, Losch de Oliveira D, Rocha JB (2012) Cd modifies hepatic Zn deposition and modulates delta-ALA-D activity and MT levels by distinct mechanisms. J Appl Toxicol 32(1):20–25.  https://doi.org/10.1002/jat.1648 CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.LR11ES41: Génétique, Biodiversité et Valorisation des Bioressources, Institut de BiotechnologieUniversité de MonastirMonastirTunisia
  2. 2.Laboratoire de Biochimie et Toxicologie EnvironnementaleISASousseTunisia
  3. 3.Institut de BiotechnologieImed MESSAOUDIMonastirTunisia

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