Thorium exerts hazardous effects on some neurotransmitters and thyroid hormones in adult male rats

Abstract

Assessment of the hazardous effects of thorium, a naturally radioactive element, on the nervous and endocrine systems, which are intimately involved in maintaining homeostasis, is important. In the present study, rats were divided into control and thorium groups and were decapitated after 2, 4, and 6 weeks. We observed that intraperitoneally injected thorium (6.3 mg/kg body weight) crossed the blood–brain barrier and was localized in the cerebellum, cerebral cortex, and hypothalamus of the rats in the given order. Thorium administration significantly decreased the GSH level and increased MDA, NO, and Fe3+ levels. Furthermore, thorium administration decreased NE and DA levels and induced fluctuations in 5-HT level. Thorium administration also increased serum TSH level, which in turn increased T4 and T3 levels. Together, these results indicate that thorium administration stimulates TSH secretion, which significantly increases T4 and T3 secretion from the thyroid gland. Moreover, these results indicate that thorium administration exerts hazardous effects on the neuroendocrine axis.

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References

  1. Abou-Donia MB, Dechkovskaia AM, Goldstein LB, Shah DU, Bullman SL, Shan WA (2002) Uranyl acetate-induced sensorimotor deficit and increased nitric oxide generation in the central nervous system in rats. Pharmacol Biochem Behav 72:881–890

    CAS  PubMed  Google Scholar 

  2. Agharanya JC (1990) Clinical usefulness of ELISA technique in the assessment of thyroid function. Weat Afr J Med 9(4):258–263

    CAS  Google Scholar 

  3. Ali M, Kumar A, Pandey BN (2014) Thorium induced cytoproliferative effect in human liver cell HepG2: role of insulin-like growth factor 1 receptor and downstream signaling. Chem Biol Interact 211:29–35

    CAS  PubMed  Google Scholar 

  4. Angoa-Pérez M, Kane MJ, Briggs DI, Herrera-Mundo N, Sykes CE, Francescutti DM, Kuhn DM (2014) Mice genetically depleted of brain serotonin do not display a depression-like behavioral phenotype. ACS Chem Neurosci 5:908–919

    PubMed  PubMed Central  Google Scholar 

  5. ATSDR (Agency for Toxic Substances and Disease Registry) (2014) Public Health Statement for Thorium

  6. Berkels R, Purol-Schnabel S, Roesen R (2004) Measurement of nitric oxide by reconversion of nitrate/nitrite to NO. Methods Mol Biol 279:1–8

    CAS  PubMed  Google Scholar 

  7. Bloom FE (2006) Neurotransmission and the central nervous system. In: the pharmacological basis of therapeutics. Lazo, JS, Parker KL (Eds). New York, The McGraw-Hill Companies, chapter 12:317–341

    Google Scholar 

  8. Briner W, Murray J (2005) Effects of short-term and long-term depleted uranium exposure on open-field behavior and brain lipid oxidation in rats. Neurotoxicol Teratol 27:135–144

    CAS  PubMed  Google Scholar 

  9. Chen HJ, Meites J (1975) Effects of biogenic amines and TRH on release of prolactin and TSH in the rat. Endocrinology 96:10–14

    CAS  PubMed  Google Scholar 

  10. Chitra KC, Latchoumycandane C, Mathur PP (2003) Induction of oxidative stress by bisphenol a in the epididymal sperm of rats. Toxicology 14:119–127

    Google Scholar 

  11. Choksi NY, Jahnke JD, Hilaire CS, Shelby M (2003) Role of thyroid hormones in human and laboratory animal reproductive health. Birth Defects Res (Part B) 68:479–491

    CAS  Google Scholar 

  12. Cicik B, Engin K (2005) The effects of cadmium on levels of glucose in serum and glycogen reserves in the liver and muscle tissues of Cyprinus carpio (L., 1758). Turk J Vet Arum Sci 29:113–117

    CAS  Google Scholar 

  13. Correa LM, Kochhann D, Becker AG, Pavanato MA, Llesuy SF, Loro VL, Raabe A, Mesko MF, Flores ÉMM, Dressler VL, Baldisserotto B (2008) Biochemistry, cytogenetics and bioaccumulation in silver catfish (Rhamdia quelen) exposed to different thorium concentrations. Aquat Toxicol 88:250–256

    CAS  PubMed  Google Scholar 

  14. Cowart JB, Burnett WC (1994) The distribution of uranium and thorium decay series radionuclides in the environment – a review. J Environ Qual 23:651–662

    CAS  Google Scholar 

  15. Crofton KM (2007) Thyroid disrupting chemicals: mechanisms and mixtures. Int J Androl 31:209–223

    Google Scholar 

  16. DiRenzo G, Gillham B, Holmes MC, Jones MT (1979) The effect of pretreatment with intraventricular 6-hydroxydopamine on hypothalamo-pituitary adrenocortical function in the rat. J Physiol 293:5–5 IP

    Google Scholar 

  17. Dotan Y, Lichtenberg D, Pinchuk I (2004) Lipid peroxidation cannot be used as a universal criterion of oxidative stress. Prog Lipid Res 43(3):200–227

    CAS  PubMed  Google Scholar 

  18. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    CAS  PubMed  Google Scholar 

  19. Engvall E, Jonsson K, Perlmann D (1971) Enzyme-linked immunosorbent assay II. Quantitative assay of protein antigen, immunoglobulin G, by means of enzyme-labelled antigen and antibody coated tubes. Biochim Biophys Acta 252(3):427–434

    Google Scholar 

  20. FAO “Food Administration Organization” (1992) Committee for Inland fisheries of Africa. Report of the third session of the working party on pollution and Hisheries. Accra, 25–29

  21. Furukawa K, Preston D, Funamoto S, Yonehara S, Ito M, Tokuoka S, Sugiyama H, Soda M, Ozasa K, Mabuchi K (2013) Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure. Int J Cancer 132:1222–1226

    CAS  PubMed  Google Scholar 

  22. Glover SE, Traub RJ, Grimm CA, Filpy RH (2001) Distribution of natural thorium in the tissues of a whole body. Radiat Prot Dosim 97(2):153–160

    CAS  Google Scholar 

  23. Glowinski LJ, Iversen LL (1966) Regonal studies of catecholamines in the rat brain. I. Disposition of [3H] noradrenaline, [3H] dopamine and [3H] dopa in various regions of brain. J Neurochem 13:655–669

    CAS  PubMed  Google Scholar 

  24. Gonzalez-Vasconcellos I, Domke T, Kuosaite V, Esposito I, Sanli-Bonazzi B, Nathrath M, Atkinson MJ, Rosemann M (2011) Differential effects of genes of the Rb1signalling pathway on osteosarcoma incidence and latency in alpha-particle irradiated mice. Radiat Environ Biophys 50(1):135–141

    CAS  PubMed  Google Scholar 

  25. Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828

    CAS  PubMed  Google Scholar 

  26. Helaly O, Abd El-Ghany M, Borai E et al (2015) Separation of cerium, light and heavy rare earth concentrates from Egyptian crude monazite. Chem Tech Ind J 10(5):184–192

    Google Scholar 

  27. Herrera JL, Vigneulle RM, Gage T, MacVittie TJ, Nold JB, Dubois A (1995) Effect of radiation and radioprotection on small intestinal function in canines. Dig Dis Sci 40:211–218

    CAS  PubMed  Google Scholar 

  28. Ismail SA, Ali FM, Hassan HMM, Abd El-Rahman D (2015) Effect of exposure to electromagnetic fields (Emfs) on monoamine neurotransmitters of newborn rats. Biochem Physiol 4(2):1–7

    Google Scholar 

  29. Jordan D, Ponet C, Mornex R, Ponsin G (1978) Participation of serotonin in thyrotropin release: evidence for the action of serotonin on thyrotropin releasing hormone release. Endocrinology 103:414–419

    CAS  PubMed  Google Scholar 

  30. Joyce JN, Loescher SK, Marshall JF (1985) Dopamine D-2 receptors in rat caudate-putamen: the lateral to medial gradient does not correspond to dopaminergic innervation. Brain Res 338:209–218

    CAS  PubMed  Google Scholar 

  31. Jung JH, Jung J, Kim SK, Woo SH, Kang KM et al (2015) Alpha lipoic acid attenuates radiation-induced thyroid injury in rats. PLoS One 10(6):1–10

    Google Scholar 

  32. Kim HS, Paik MJ, Kim YJ, Lee G, Lee Y, Choi H, Kim BC, Pack J, Kim N, Ahn YH (2013) Effects of whole-body exposure to 915 MHz RFID on secretory functions of the thyroid system in rats. Bioelectromagnet 34(7):521–529

    CAS  Google Scholar 

  33. Kovacic P, Jacintho JD (2001) reproductive toxins, pervasive theme of oxidative stress and electron transfer. Curr Med Chem 8:863–892

    CAS  PubMed  Google Scholar 

  34. Kumar A, Mishra P, Ghosh S, Sharma P, Ali M, Pandey BN, Mishra KP (2008) Thorium-induced oxidative stress mediated toxicity in mice and its abrogation by diethylenetriamine pentaacetate. Int J Radiat Biol 84(4):337–349

    CAS  PubMed  Google Scholar 

  35. Kumar A, Ali M, Mishra P, Pandey BN, Sharma P, Mishra KP (2009) Thorium-induced neurobehavioural and neurochemical alterations in Swiss mice. Int J Radiat Biol 85(4):338–347

    CAS  PubMed  Google Scholar 

  36. Kumar A, Ali M, Pandey B, Hassan P, Mishra M (2010) Role of membrane sialic acid and glycophorin protein in thorium induced aggregation and hemolysis of human erythrocytes. Biochimie 92:869–879

    CAS  PubMed  Google Scholar 

  37. Kumar A, Ali M, Pandey B (2013) Understanding the biological effects of thorium and developing efficient strategies for its Decorporation and mitigation. Bark Newslett 335:55–56

    Google Scholar 

  38. Langmuir D, Herman JS (1980) The mobility of thorium in natural waters at low temperatures. Geochim Cosmochim Acta 44:1753–1766

    CAS  Google Scholar 

  39. Likhachev IP (1976) Pathological anatomy, etiology and pathogenesis of remote sequelae of radiation dust exposure. Arkh Patol 38:18–26 [Russian]

    CAS  PubMed  Google Scholar 

  40. Loganovsky KN, Yuryev KL (2004) EEG patterns in persons exposed to ionized radiation as a result of the Chernobyl accident. Part 2 quantitative EEG analysis in patient who had acute radiation sickness. J Neuropsychiatry Clin Neurosci 16:70–82

    PubMed  Google Scholar 

  41. Low MJ (2011) Neuroendocrinology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (eds) Williams textbook of endocrinology, 12th edn. Elsevier/Saunders, Philadelphia, pp 103–174

    Google Scholar 

  42. Marakhtanov MK, Okunev VS (2018) The collective radioactive decay of atomic nuclei initiated by an external mechanical impact: science fiction or a new class of physical processes. J Mater Sci Res 7(2):34–50

    CAS  Google Scholar 

  43. Marczenko Z (1986) Thorium in separation and spectrophotometric determination of elements. Ellis Harwood Ltd, Chichester, pp 576–580

    Google Scholar 

  44. Martin AB, Fernandez-Espejo E, Ferrer B et al (2008) Expression and function of CB1 receptor in the rat striatum: localization and effects on D1 and D2 dopamine receptor-mediated motor behaviors. Neuropsychopharmacology 33:1667–1679

    CAS  PubMed  Google Scholar 

  45. McClinton LT, Schubert J (1948) The toxicity of some zirconium and thorium salt in rats. J Pharmacol Exp Ther:1–6

  46. Morley JE, Bramme JL, Sharp B et al (1981) Neurotransmitter control of hypothalamic-pituitary-thyroid function in rats. Eur J Pharmacol 70:263–271

    CAS  PubMed  Google Scholar 

  47. Mueller GP, Simpkins J, Meites J, Moore KE (1976) Differential effects of dopamine agonists and haloperidol on the release of prolactin, thyroid stimulating hormone, growth hormone and luteinizing hormone in rats. Neuroendocrinology 20:121–135

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  49. Pagel M, Lutzoni F (2002) According for phylogenetic uncertainty in comparative studies of evaluation and adaptation. In: Laesin M, Valleriani A (eds) Biological evaluation and statical physics. Springer Verlag, Berlin

    Google Scholar 

  50. Pausescu E, Cotutiu C, Tomescu E, Patru A (1973) Electron Optic Morphological and Cytochemical Evidence in Support of a ‘Cytoplasmic’ Solution for Kidney Preservation. Eur Surg Res 5:438–453

    CAS  PubMed  Google Scholar 

  51. Peng C, Ma Y, Ding Y et al (2017) Influence of speciation of thorium on toxic effects to green algae Chlorella pyrenoidosa. Int J Mol Sci 18:1–10

    Google Scholar 

  52. Perrone S, Santacroce A, Longini M, Proietti F, Bazzini F, Buonocore G (2018) The free radical diseases of prematurity: from cellular mechanisms to bedside. Oxidative Med Cell Longev 2018:1–14

    Google Scholar 

  53. Rezk MM (2018) A neuro-comparative study between single/successive thorium dose intoxication and alginate treatment. Biol Trace Elem Res 185:414–423

    CAS  PubMed  Google Scholar 

  54. Rezk MM, Mohamed AA, Ammar AA (2018) Thorium harmful impacts on the physiological parameters of the adult male albino rats and their mitigation using the alginate. Toxicol Environ Health Sci 10(5):253–260

    Google Scholar 

  55. Schlemmer HP, Liebermann D, Naser V, Van Kaick G (2000) Locoregional late effects of paravascular Thorotrast deposits: results of the German Thorotrast study. J Neuroradiol 27(4):253–263

    CAS  PubMed  Google Scholar 

  56. Sharp B, Morley JE, Carlson HE et al (1980) Morphine suppression of thyrotropin is dopamine dependent. Clin Res 28:26A

    Google Scholar 

  57. Toichuev R, Toichueva G, Madykova J et al (2013) Characteristics of the level of thyroid hormones without clinical manifestations of goiter in population living in uranium biogeochemical. Environ Health Perspect 2013(1):1–20

    Google Scholar 

  58. Veado MARV, Arantes IA, Oliveira AH, Almeida MRMG, Miguel RA, Severo MI, Cabaleiro HL (2006) Metal pollution in the environment of Minas Gerais state – Brazil. Environ Monit Assess 117:157–172

    CAS  PubMed  Google Scholar 

  59. Vijayan E, Krulich L, McCann SM (1978) Catecholaminergic regulation in TSH and growth hormone release in ovariectomized and ovariectomized steroid-primed rats. Neuroendocrinology 26:176

    Google Scholar 

  60. Villegas G, Fernandez J (1966) Permeability to thorium dioxide of the intercellular spaces of the frog cerebral hemisphere. Expe Neurol 15:18–36

    CAS  Google Scholar 

  61. Yaeesh S, Jamal Q, Shah A, Gilani A (2010) Antihepatotoxic activity of Saussurea lappa extract on D-galactosamine and lipopolysaccharide-induced hepatitis in mice. Phytother Res 24:229–S232

    Google Scholar 

  62. Yamamoto Y, Kurachi M, Yamaguchi K, Oda T (2007) Stimulation of multiple cytokine production in mice by alginate oligosaccharides following intraperitoneal administration. Carbohydr Res 342(8):1133–1137

    CAS  PubMed  Google Scholar 

  63. Yamamoto Y, Chikawa J, Uegaki Y, Usuda N, Kuwahara Y, Fukumoto M (2009) Histological type of Thorotrast-induced liver tumors associated with the translocation of deposited radionuclides. Cancer Sci 11(2):336–340

    Google Scholar 

  64. Yellepeddi V (2015) Principal of drug therapy. In: Whalen K, Finkel R, Panavelil TA (eds) Lippincott illustrated reviews: pharmacology, sixth edn. Philadelphia, Baltimore, pp P1–P25

    Google Scholar 

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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MA, MR, and AE conceived and designed research. AE and SE conducted experiments. MR, AE, and OF contributed new reagents or analytical tools. SE, AE, and SE analyzed data. MA, MR, and AE wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Mohamed M. Rezk.

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The investigation protocol was approved by the ethics committee of nuclear material authority, which is performed in accordance with the ethical standards laid down in the US guidelines (NIH Publication no. 85-23, amended in 1985).

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Abdel-Rahman, M., Rezk, M.M., Abdel Moneim, A.E. et al. Thorium exerts hazardous effects on some neurotransmitters and thyroid hormones in adult male rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 167–176 (2020). https://doi.org/10.1007/s00210-019-01718-y

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Keywords

  • Thorium
  • Neurotransmitters
  • Thyroid
  • Rats