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Biol Trace Elem Res. 2021 Apr 08; doi: 10.1007/s12011-021-02709-y. Epub 2021 Apr 08.

Parental Lead Exposure Promotes Neurobehavioral Disorders and Hepatic Dysfunction in Mouse Offspring.

Biological trace element research

Hasan Ul Banna, Adiba Anjum, Sheta Biswas, Victor Mondal, Abu Eabrahim Siddique, Apurba Kumar Roy, Farjana Nikkon, Azizul Haque, Seiichiro Himeno, Kazi Abdus Salam, Khaled Hossain, Zahangir Alam Saud

Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
  2. Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Tangail, 1902, Bangladesh.
  3. Department of Biochemistry and Molecular Biology, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh.
  4. Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
  5. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
  6. Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, 770-8514, Japan.
  7. Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, 6205, Bangladesh. [email protected].

PMID: 33830404 DOI: 10.1007/s12011-021-02709-y

Abstract

Lead (Pb) induces neurotoxicity in both children and adults. Children are more vulnerable to Pb toxicity than adults. Little is known about the effects of Pb on the mental health of the children who are prenatally exposed. Therefore, we designed an animal experiment to compare the adverse effects of Pb on neurobehavioral and hepatic functions between Pb-exposed (Pb mice) and parental Pb-exposed (P-Pb mice) group mice. Mice were treated with Pb-acetate (10 mg/kg bodyweight/day) via drinking water. Male mice from unexposed parents treated with Pb for 90 days were defined as Pb mice, whereas male mice from Pb-exposed parents treated with Pb for further 90 days were defined as P-Pb mice. Anxiety-like behavior and spatial memory and learning were assessed by elevated plus maze and Morris water maze. Serum hepatic enzyme activities and butyrylcholinesterase activity were measured by an analyzer. P-Pb mice displayed increased anxiety-like behavior and memory and learning impairments compared to Pb mice. BChE activity was significantly decreased in P-Pb mice compared to Pb mice. Pb levels in the brains of P-Pb mice were significantly higher than those of Pb mice. The activities of serum hepatic enzymes of P-Pb mice were also higher than those of Pb mice. Additionally, histopathology data revealed that hepatic tissue injury was more pronounced in P-Pb mice than in Pb mice. Thus, the results suggest that persistent exposure to Pb from fetus to adult causes more severe neurobehavioral changes and hepatic toxicities than adult exposure only.

Keywords: Anxiety; Lead toxicity; Liver dysfunction; Memory impairment

References

  1. Flora G, Gupta D, Tiwari A (2012) Toxicity of lead: a review with recent updates. Interdiscip Toxicol 5(2):47–58 - PubMed
  2. Hasan MK, Shahriar A, Jim KU (2019) Water pollution in Bangladesh and its impact on public health. Heliyon 5(8):e02145 - PubMed
  3. UNICEF. Bangladesh: adolescents. Available at: http://www.unicef.org/bangladesh/children 356.htm . Accessed 6 Oct 2008 - PubMed
  4. Mitra AK, Haque A, Islam M, Bashar SA (2009) Lead poisoning: an alarming public health problem in Bangladesh. Int J Environ Res Public Health 6(1):84–95 - PubMed
  5. Kaiser R, Henderson AK, Daley WR, Naughton M, Khan MH, Rahman M, Kieszak S, Rubin CH (2001) Blood lead levels of primary school children in Dhaka, Bangladesh. Environ Health Perspect 109:563–566 - PubMed
  6. Bhuiyan MA, Islam MA, Dampare SB, Parvez L, Suzuki S (2010) Evaluation of hazardous metal pollution in irrigation and drinking water systems in the vicinity of a coal mine area of northwestern Bangladesh. J Hazard Mater 179(1-3):1065–1077 - PubMed
  7. Mostafa MG, Uddin SMH, Haque ABMH (2017) Assessment of hydro-geochemistry and groundwater quality of Rajshahi City in Bangladesh. Appl Water Sci 7:4663–4671 - PubMed
  8. WHO, Regional Office for South-East Asia (2002) Country health system profile: Bangladesh. Available from: http://www.who.int/gho/countries/bgd/country_profiles/en/ . Accessed 5 Jan 2021 - PubMed
  9. Dumková J, Smutná T, Vrlíková L, Le Coustumer P, Večeřa Z, Dočekal B, Mikuška P, Čapka L, Fictum P, Hampl A, Buchtová M (2017) Sub-chronic inhalation of lead oxide nanoparticles revealed their broad distribution and tissue-specific subcellular localization in target organs. Part Fibre Toxicol 14(1):55 - PubMed
  10. Kasten-Jolly J, Pabello N, Bolivar VJ, Lawrence DA (2012) Developmental lead effects on behavior and brain gene expression in male and female BALB/cAnNTac mice. Neurobehav Toxicol 33(5):1005–1020 - PubMed
  11. Weisskopf MG, Proctor SP, Wright RO, Schwartz J, Spiro A 3rd, Sparrow D, Nie H, Hu H (2007) Cumulative lead exposure and cognitive performance among elderly men. Epidemiology 18(1):59–66 - PubMed
  12. Basha R, Reddy GR (2010) Developmental exposure to lead and late life abnormalities of nervous system. Indian J Exp Biol 48:636–641 - PubMed
  13. Athanasopoulos D, Karagiannis G, Tsolaki M (2016) Recent findings in Alzheimer disease and nutrition focusing on epigenetics. Adv Nutr 7(5):917–927 - PubMed
  14. Gupta VK, You Y, Gupta VB, Klistorner A, Graham SL (2013) TrkB receptor signaling: implications in neurodegenerative, psychiatric and proliferative disorders. Int J Mol Sci 14(5):10122–10142 - PubMed
  15. Sanders T, Liu Y, Buchner V, Tchounwou PB (2009) Neurotoxic effects and biomarkers of lead exposure: a review. Rev Environ Health 24(1):15–45 - PubMed
  16. (2012) Committee opinion No. 533: lead screening during pregnancy and lactation. Comm Obstetr Pract Obstet Gynecol 120(2 Pt 1):416–20 - PubMed
  17. Chen XK, Yang Q, Smith G, Krewski D, Walker M, Wen SW (2006) Environmental lead level and pregnancy-induced hypertension. Environ Res 100(3):424–430 - PubMed
  18. Pal M, Sachdeva M, Gupta N, Mishra P, Yadav M, Tiwari A (2015) Lead exposure in different organs of mammals and prevention by curcumin–nanocurcumin: a review. Biol Trace Elem Res 168(2):380–391 - PubMed
  19. Zhu G, Fan G, Feng C, Li Y, Chen Y, Zhou F, Du G, Jiao H, Liu Z, Xiao X, Lin F (2013) The effect of lead exposure on brain iron homeostasis and the expression of DMT1/FP1 in the brain in developing and aged rats. Toxicol Lett 216(2-3):108–123 - PubMed
  20. Chiodo LM, Jacobson SW, Jacobson JL (2004) Neurodevelopmental effects of postnatal lead exposure at very low levels. Neurotoxicol Teratol 26(3):359–371 - PubMed
  21. Vigeh M, Yokoyama K, Kitamura F, Afshinrokh M, Beygi A, Niroomanesh S (2010) Early pregnancy blood lead and spontaneous abortion. Women Health 50(8):756–766 - PubMed
  22. Dursun A, Yurdakok K, Yalcin SS, Tekinalp G, Aykut O, Orhan G, Morgil GK (2016) Maternal risk factors associated with lead, mercury and cadmium levels in umbilical cord blood, breast milk and newborn hair. J Matern Fetal Neonatal Med 29(6):954–961 - PubMed
  23. Liu J, Liu X, Wang W, McCauley L, Pinto-Martin J, Wang Y, Li L, Yan C, Rogan WJ (2014) Blood lead levels and children’s behavioral and emotional problems: a cohort study. JAMA Pediatr 168(8):737–745 - PubMed
  24. Hauptman M, Bruccoleri R, Woolf AD (2017) An update on childhood lead poisoning. Clin Pediatr Emerg Med 18(3):181–192 - PubMed
  25. Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, Canfield RL, Dietrich KN, Bornschein R, Greene T, Rothenberg SJ, Needleman HL, Schnaas L, Wasserman G, Graziano J, Roberts R (2005) Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ Health Perspect 113(7):894–899 - PubMed
  26. Canfield RL, Henderson CR, Jr Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP (2003) Intellectual impairment in children with blood lead concentrations below 10 μg/dL. N Engl J Med 348:1517–1526 - PubMed
  27. Jarrar BM, Taib NT (2012) Histological and histochemical alterations in the liver induced by lead chronic toxicity. Saudi J Biol Sci 19(2):203–210 - PubMed
  28. Khan DA, Qayyum S, Saleem S, Khan FA (2008) Lead-induced oxidative stress adversely affects health of the occupational workers. Toxicol Ind Health 24(9):611–618 - PubMed
  29. Feng Y, Wang N, Ye X, Li H, Feng Y, Cheung F, Nagamatsu T (2011) Hepatoprotective effect and its possible mechanism of Coptidisrhizoma aqueous extract on carbon tetrachloride-induced chronic liver hepatotoxicity in rats. J Ethnopharmacol 138:683–690 - PubMed
  30. Singal AK, Jampana SC, Weinman SA (2011) Antioxidants as therapeutic agents for liver disease. Liver Int 31(10):1432–1448 - PubMed
  31. Rashid H, Mahboob A, Ahmed T (2017) Role of cholinergic receptors in memory retrieval depends on gender and age of memory. Behav Brain Res 331:233–240 - PubMed
  32. Aktar S, Jahan M, Alam S, Mohanto NC, Arefin A, Rahman A, Haque A, Himeno S, Hossain K, Saud ZA (2017) Individual and combined effects of arsenic and lead on behavioral and biochemical changes in mice. Biol Trace Elem Res 177(2):288–296 - PubMed
  33. Seddik L, Bah TM, Aoues A, Brnderdour M, Silmani M (2010) Dried leaf extract protects against lead-induced neurotoxicity in Wistar rats. Eur J Sci Res 42(1):139–151 - PubMed
  34. Biswas S, Banna HU, Jahan M, Anjum A, Siddique AE, Roy A, Nikkon F, Salam KA, Haque A, Himeno S, Hossain K, Saud ZA (2020) In vivo evaluation of arsenic-associated behavioral and biochemical alterations in F - PubMed
  35. Xu Y, Li G, Han C, Sun L, Zhao R, Cui S (2005) Protective effects of Hippophae rhamnoides L. juice on lead-induced neurotoxicity in mice. Biol Pharm Bull 28(3):490–494 - PubMed
  36. Mishra M, Acharya UR (2004) Protective action of vitamins on the spermatogenesis in lead-treated Swiss mice. J Trace Elem Med Biol 18(2):173–178 - PubMed
  37. Kasten-Jolly J, Lawrence DA (2017) Sex-specific effects of developmental lead exposure on the immune-neuroendocrine network. Toxicol Appl Pharmacol 334:142–157 - PubMed
  38. Singh G, Singh V, Sobolewski M, Cory-Slechta DA, Schneider JS (2018) Sex-dependent effects of developmental lead exposure on the brain. Front Genet 9:89 - PubMed
  39. Richter SH, Kästner N, Loddenkemper DH, Kaiser S, Sachser N (2016) A time to wean? Impact of weaning age on anxiety-like behaviour and stability of behavioural traits in full adulthood. PLoS One 11(12):e0167652 - PubMed
  40. Koehl M, Lemaire V, Vallée M, Abrous N, Piazza PV, Mayo W, Maccari S, Le Moal M (2001) Long term neurodevelopmental and behavioral effects of perinatal life events in rats. Neurotox Res 3(1):65–83 - PubMed
  41. Schneider P, Ho YJ, Spanagel R, Pawlak CR (2011) A novel elevated plus-maze procedure to avoid the one-trial tolerance problem. Front Behav Neurosci 5:43 - PubMed
  42. Carobrez AP, Bertoglio LJ (2005) Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on. Neurosci Biobehav Rev 29(8):1193–1205 - PubMed
  43. Caldarone BJ, King SL, Picciotto MR (2008) Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice. Neurosci Lett 439(2):187–191 - PubMed
  44. Barnhart CD, Yang D, Lein PJ (2015) Using the Morris water maze to assess spatial learning and memory in weanling mice. PLoS One 10(4):e0124521 - PubMed
  45. Woreta TA, Alqahtani SA (2014) Evaluation of abnormal liver tests. Med Clin 98(1):1–6 - PubMed
  46. Anjum A, Biswas S, Rahman M, Rahman A, Siddique AE, Karim Y, Aktar S, Nikkon F, Haque A, Himeno S, Hossain K, Saud ZA (2019) Butyrylcholinesterase-a potential plasma biomarker in manganese-induced neurobehavioral changes. Environ Sci Pollut Res 26(7):6378–6387 - PubMed
  47. Dong MX, Xu XM, Hu L, Liu Y, Huang YJ, Wei YD (2017) Serum butyrylcholinesterase activity: a biomarker for Parkinson’s disease and related dementia. Biomed Res Int 2017:1524107 - PubMed
  48. Biswas S, Anjum A, Banna HU, Rahman M, Siddique AE, Karim Y, Nikkon F, Haque A, Hossain K, Saud ZA (2019) Manganese attenuates the effects of arsenic on neurobehavioral and biochemical changes in mice co-exposed to arsenic and manganese. Environ Sci Pollut Res 26(28):29257–29266 - PubMed
  49. Noman AS, Dilruba S, Mohanto NC, Rahman L, Khatun Z, Riad W, Al Mamun A, Alam S, Aktar S, Chowdhury S, Saud ZA, Rahman Z, Hossain K, Haque A (2015) Arsenic-induced histological alterations in various organs of mice. J Cytol Histol 6(3):323 - PubMed
  50. Mason LH, Harp JP, Han DY (2014) Pb neurotoxicity: neuropsychological effects of lead toxicity. Biomed Res Int 2014:840547 - PubMed
  51. Barkur RR, Bairy LK (2015) Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development. Int J Occup Med Environ Health 28(3):533–544 - PubMed
  52. Kahloula K, Slimani M, Aoues A (2009) Behavioural and neurochemical studies of perinatal lead exposed in rat Wistar. Eur J Sci Res 35:603–661 - PubMed
  53. Leret ML, Millan JAS, Antonio MT (2003) Perinatal exposure to lead and cadmium affects anxiety-like behavior. Toxicology 186(1-2):125–130 - PubMed
  54. Darvesh S (2016) Butyrylcholinesterase as a diagnostic and therapeutic target for Alzheimer’s disease. Curr Alzheimer Res 13(10):1173–1177 - PubMed
  55. Santarpia L, Grandone I, Contaldo F, Pasanisi F (2013) Butyrylcholinesterase as a prognostic marker: a review of the literature. J Cachexia Sarcopenia Muscle 4(1):31–39 - PubMed
  56. Bono GF, Simão-Silva DP, Batistela MS, Josviak ND, Dias PF, Nascimento GA, Souza RL, Piovezan MR, Souza RK, Furtado-Alle L (2015) Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer’s disease in a Southern Brazilian population. Neurochem Int 81:57–62 - PubMed
  57. Lockridge O (2015) Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses. Pharm Ther 148:34–46 - PubMed
  58. Peres TV, Schettinger MR, Chen P, Carvalho F, Avila DS, Bowman AB, Aschner M (2016) Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies. BMC Pharmacol Toxicol 17(1):57 - PubMed
  59. Darvesh S, Reid GA (2016) Reduced fibrillar β-amyloid in subcortical structures in a butyrylcholinesterase-knockout Alzheimer disease mouse model. Chem Biol Interact 259:307–312 - PubMed
  60. Reid GA, Darvesh S (2015) Butyrylcholinesterase-knockout reduces brain deposition of fibrillar β-amyloid in an Alzheimer mouse model. Neuroscience 298:424–435 - PubMed
  61. Antonio MT, Corredor L, Leret ML (2003) Study of the activity of several brain enzymes like markers of the neurotoxicity induced by perinatal exposure to lead and/or cadmium. Toxicol Lett 143(3):331–340 - PubMed
  62. Reddy GR, Devi CB, Chetty CS (2007) Developmental lead neurotoxicity: alterations in brain cholinergic system. Neuro Toxicol 28(2):402–407 - PubMed
  63. Sun L, Zhao ZY, Hu J, Zhou XL (2005) Potential association of lead exposure during early development of mice with alteration of hippocampus nitric oxide levels and learning memory. Biomed Environ Sci 18(6):375–378 - PubMed
  64. Yadav RS, Chandravanshi LP, Shukla RK, Sankhwar ML, Ansari RW, Shukla PK, Pant AB, Khanna VK (2011) Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats. Neurotoxicology 32(6):760–768 - PubMed
  65. Rodríguez VM, Carrizales L, Jiménez-Capdeville ME, Dufour L, Giordano M (2001) The effects of sodium arsenite exposure on behavioral parameters in the rat. Brain Res Bull 55(2):301–308 - PubMed
  66. Rodríguez VM, Jiménez-Capdeville ME, Giordano M (2003) The effects of arsenic exposure on the nervous system. Toxicol Lett 145(1):1–18 - PubMed
  67. Flora SJ, Mittal M, Mishra D (2009) Co-exposure to arsenic and fluoride on oxidative stress, glutathione linked enzymes, biogenic amines and DNA damage in mouse brain. J Neurol Sci 285(1-2):198–205 - PubMed
  68. Wang J, Wu J, Zhang Z (2006) Oxidative stress in mouse brain exposed to lead. Ann Occup Hyg 50(4):405–409 - PubMed
  69. Patki G, Solanki N, Atrooz F, Allam F, Salim S (2013) Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res 1539:73–86 - PubMed
  70. Allam F, Dao AT, Chugh G, Bohat R, Jafri F, Patki G, Mowrey C, Asghar M, Alkadhi KA, Salim S (2013) Grape powder supplementation prevents oxidative stress-induced anxiety-like behavior, memory impairment, and high blood pressure in rats. J Nutr 143(6):835–842 - PubMed
  71. Zhao ZH, Zheng G, Wang T, Du K, Han X, Luo Z, Shen X, Chen J (2018) Low-level gestational lead exposure alters dendritic spine plasticity in the hippocampus and reduces learning and memory in rats. Sci Rep 8(1):3533 - PubMed
  72. Ahmad F, Salahuddin M, Alsamman K, AlMulla AA, Salama KF (2018) Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation. Neuropsychiatr Dis Treat 14:3289–3298 - PubMed
  73. Buffington SA, Huang W, Costa-Mattioli M (2014) Translational control in synaptic plasticity and cognitive dysfunction. Annu Rev Neurosci 37(1):17–38 - PubMed
  74. Neal AP, Stansfield KH, Worley PF, Tompson RE, Guilarte TR (2010) Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: potential role of NMDA receptor-dependent BDNF signaling. Toxicol Sci 116(1):249–263 - PubMed
  75. Piñeiro-Carrero VM, Piñeiro EO (2004) Liver. Liver Pediatr 113:1097–1106 - PubMed
  76. Nehru B, Kaushal S (1993) Alterations in the hepatic enzymes following experimental lead poisoning. Biol Trace Elem Res 38(1):27–34 - PubMed
  77. Taib NT, Jarrar BM, Mubarak M (2004) Ultrastructural alterations in hepatic tissues of white rats (Rattus norvegicus) induced by lead experimental toxicity. Saudi J Biol Sci 11(1):11–20 - PubMed
  78. Shinozoka H, Ohmura T, Katyal S, Zedda A, Ledda-Columbano G, Columbano A (1996) Possible roles of nonparenchymal cells in hepatocyte proliferation induced by lead nitrate and by tumor necrosis factor alpha. Hepatology 23(8):1572–1577 - PubMed
  79. Faulk C, Barks A, Liu K, Goodrich JM, Dolinoy DC (2013) Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice. Epigenomics 5(5) - PubMed
  80. Dou JF, Farooqui Z, Faulk CD, Barks AK, Jones T, Dolinoy DC, Bakulski KM (2019) Perinatal lead (Pb) exposure and cortical neuron-specific DNA methylation in male mice. Genes (Basel) 10(4):274 - PubMed

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