Skip to main content
Log in

Potential Role of Oxidative Stress in the Effects of Chronic Administration of Iron on Affective and Cognitive Behavior on Male Wistar Rat

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

In this work, we studied the impact of chronic iron exposure, in the form of iron sulfate (FeSo4), on affective and cognitive disorders and oxidative stress in the male Wistar rat. The treatment was carried out for 8 weeks, the rats received an intraperitoneal injection of iron at different doses: 0.25, 0.5, and 1 mg/kg. Affective and cognitive disorders are assessed in open field test (OFT), elevated plus maze (EPM), forced swimming test (FST), Morris water maze (MWM), and Y-maze. The hippocampus and prefrontal cortex of each animal were taken for biochemical examination. Our results show that iron exerts anxiogenic and depressogenic effects, which were observed first at the dose of 0.5 mg/kg and continued in a dose-dependent manner up to the maximum tested dose of 1 mg/kg. According to results from the MWM and Y-maze tests, continuous exposure to iron induces cognitive disorders that are defined by the disturbance of working memory and influences spatial learning performance causing a deficit of spatial memory retention. We noted that chronic exposure to iron can be associated with the appearance of a state of oxidative stress in the hippocampus and the prefrontal cortex demonstrated by an increase in lipid peroxidation, an increase in nitric oxide, and also by disturbances in the antioxidant defense systems following a determination of the concentrations of catalase. In conclusion, we can deduce from this work that chronic iron exposure can be related to the induction of cognitive and affective disorders and oxidative stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ (2012) Heavy metal toxicity and the environment. Mol Clin Environ Toxicol 101:133–164. https://doi.org/10.1007/978-3-7643-8340-4_6

    Article  Google Scholar 

  2. Lamtai M, Ouakki S, Zghari O, Mesfioui A, El Hessni A, Ouichou A (2019) Affective behavior dysregulation was induced by chronic administration of copper in Wistar rats. Neurosci Med 10(02):134–149. https://doi.org/10.4236/nm.2019.102009

    Article  CAS  Google Scholar 

  3. Zghari O et al (2018) Effect of chronic aluminum administration on affective and cognitive behavior in male and female rats. J Behav Brain Sci 08(04):179–196. https://doi.org/10.4236/jbbs.2018.84012

    Article  CAS  Google Scholar 

  4. Lamtai M et al (2018) Effect of chronic administration of nickel on affective and cognitive behavior in male and female rats: Possible implication of oxidative stress pathway. Brain Sci 8:8. https://doi.org/10.3390/brainsci8080141

    Article  CAS  Google Scholar 

  5. Lamtai M et al (2018) Effect of chronic administration of cadmium on anxiety-like, depression-like and memory deficits in male and female rats: possible involvement of oxidative stress mechanism. J Behav Brain Sci 08(05):240–268. https://doi.org/10.4236/jbbs.2018.85016

    Article  CAS  Google Scholar 

  6. El Brouzi MY et al (2021) Intrahippocampal effects of nickel injection on the affective and cognitive response in Wistar rat: potential role of oxidative stress. Biol Trace Elem Res 199(9):3382–3392. https://doi.org/10.1007/s12011-020-02457-5

    Article  CAS  PubMed  Google Scholar 

  7. de Lima MNM et al (2007) Desferoxamine reverses neonatal iron-induced recognition memory impairment in rats. Eur J Pharmacol 570(1–3):111–114. https://doi.org/10.1016/j.ejphar.2007.06.002

    Article  CAS  PubMed  Google Scholar 

  8. da Silva PF et al (2012) Memory impairment induced by brain iron overload is accompanied by reduced H3K9 acetylation and ameliorated by sodium butyrate. Neuroscience 200:42–49. https://doi.org/10.1016/j.neuroscience.2011.10.038

    Article  CAS  PubMed  Google Scholar 

  9. Lozoff B, Castillo M, Clark KM, Smith JB (2012) Iron-fortified vs low-iron infant formula: Developmental outcome at 10 years. Arch Pediatr Adolesc Med 166(3):208–215. https://doi.org/10.1001/archpediatrics.2011.197

    Article  PubMed  Google Scholar 

  10. Railey AM, Groeber CM, Flinn JM (2011) The effect of metals on spatial memory in a transgenic mouse model of alzheimer’s disease. J Alzheimer’s Dis 24(2):375–381. https://doi.org/10.3233/JAD-2011-101452

    Article  CAS  Google Scholar 

  11. Guo C, Wang T, Zheng W, Shan ZY, Teng WP, Wang ZY (2013) Intranasal deferoxamine reverses iron-induced memory deficits and inhibits amyloidogenic APP processing in a transgenic mouse model of Alzheimer’s disease. Neurobiol Aging 34(2):562–575. https://doi.org/10.1016/j.neurobiolaging.2012.05.009

    Article  CAS  PubMed  Google Scholar 

  12. Rech RL et al (2010) Reversal of age-associated memory impairment by rosuvastatin in rats. Exp Gerontol 45(5):351–356. https://doi.org/10.1016/j.exger.2010.02.001

    Article  CAS  PubMed  Google Scholar 

  13. Perez V et al (2010) Iron leads to memory impairment that is associated with a decrease in acetylcholinesterase pathways. Curr Neurovasc Res 7(1):15–22. https://doi.org/10.2174/156720210790820172

    Article  CAS  PubMed  Google Scholar 

  14. De Lima MNM et al (2005) Selegiline protects against recognition memory impairment induced by neonatal iron treatment. Exp Neurol 196(1):177–183. https://doi.org/10.1016/j.expneurol.2005.07.017

    Article  CAS  PubMed  Google Scholar 

  15. de Lima MN et al (2008) Amelioration of recognition memory impairment associated with iron loading or aging by the type 4-specific phosphodiesterase inhibitor rolipram in rats. Neuropharmacology 55(5):788–792. https://doi.org/10.1016/j.neuropharm.2008.06.025

    Article  CAS  PubMed  Google Scholar 

  16. De Lima MNM et al (2005) Recognition memory impairment and brain oxidative stress induced by postnatal iron administration. Eur J Neurosci 21(9):2521–2528. https://doi.org/10.1111/j.1460-9568.2005.04083.x

    Article  PubMed  Google Scholar 

  17. Maaroufi K, Ammari M, Jeljeli M, Roy V, Sakly M, Abdelmelek H (2009) Impairment of emotional behavior and spatial learning in adult Wistar rats by ferrous sulfate. Physiol Behav 96(2):343–349. https://doi.org/10.1016/j.physbeh.2008.10.019

    Article  CAS  PubMed  Google Scholar 

  18. Schröder N, Fredriksson A, Vianna MRM, Roesler R, Izquierdo I, Archer T (2001) Memory deficits in adult rats following postnatal iron administration. Behav Brain Res 124(1):77–85. https://doi.org/10.1016/S0166-4328(01)00236-4

    Article  PubMed  Google Scholar 

  19. Fredriksson A, Schröder N, Eriksson P, Izquierdo I, Archer T (2000) Maze learning and motor activity deficits in adult mice induced by iron exposure during a critical postnatal period. Dev Brain Res 119(1):65–74. https://doi.org/10.1016/S0165-3806(99)00160-1

    Article  CAS  Google Scholar 

  20. Fredriksson A, Schröder N, Eriksson P, Izquierdo I, Archer T (1999) Neonatal iron exposure induces neurobehavioural dysfunctions in adult mice. Toxicol Appl Pharmacol 159(1):25–30. https://doi.org/10.1006/taap.1999.8711

    Article  CAS  PubMed  Google Scholar 

  21. Nunes ES, Desai SN, Desai PV (2010) Effect of ferrous sulphate on aspartate and alanine aminotransferases of brain of Tilapia mossambica. Food Chem Toxicol 48(2):490–494. https://doi.org/10.1016/j.fct.2009.10.045

    Article  CAS  PubMed  Google Scholar 

  22. Gaasch JA, Lockman PR, Geldenhuys WJ, Allen DD, Van Der Schyf CJ (2007) Brain iron toxicity: Differential responses of astrocytes, neurons, and endothelial cells. Neurochem Res 32(7):1196–1208. https://doi.org/10.1007/S11064-007-9290-4

    Article  CAS  PubMed  Google Scholar 

  23. Hirsch EC, Brandel J-P, Galle P, Javoy-Agid F, Agid Y (1991) Iron and aluminum increase in the substantia nigra of patients with Parkinson’s disease: an X-ray microanalysis. J Neurochem 56(2):446–451. https://doi.org/10.1111/J.1471-4159.1991.TB08170.X

    Article  CAS  PubMed  Google Scholar 

  24. Dexter DT, Jenner P, Schapira AHV, Marsden CD (1992) Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia. Ann Neurol 32(1):S94–S100. https://doi.org/10.1002/ana.410320716

    Article  CAS  PubMed  Google Scholar 

  25. Riederer P et al (1989) Transition metals, ferritin, glutathione, and ascorbic acid in Parkinsonian brains. J Neurochem 52(2):515–520. https://doi.org/10.1111/J.1471-4159.1989.TB09150.X

    Article  CAS  PubMed  Google Scholar 

  26. Dexter DT et al (1987) Increased nigral iron content in postmortem parkinsonian brain. The Lancet 330(8569):1219–1220. https://doi.org/10.1016/S0140-6736(87)91361-4

    Article  Google Scholar 

  27. Figueiredo LS, De Lima MNM (2013) Role of brain iron accumulation in cognitive dysfunction: Evidence from animal models and human studies. J Alzheimer’s Dis 34(4):797–812. https://doi.org/10.3233/JAD-121996

    Article  CAS  Google Scholar 

  28. Berg D et al (2001) Brain iron pathways and their relevance to Parkinson’s disease. J Neurochem 79(2):225–236. https://doi.org/10.1046/j.1471-4159.2001.00608.x

    Article  CAS  PubMed  Google Scholar 

  29. Belkacemi A, Ramassamy C (2012) Time sequence of oxidative stress in the brain from transgenic mouse models of Alzheimer’s disease related to the amyloid-β cascade. Free Radic Biol Med 52(3):593–600. https://doi.org/10.1016/j.freeradbiomed.2011.11.020

    Article  CAS  PubMed  Google Scholar 

  30. Milward EA et al (2010) A cross-sectional community study of serum iron measures and cognitive status in older adults. J Alzheimer’s Dis 20(2):617–623. https://doi.org/10.3233/JAD-2010-1402

    Article  CAS  Google Scholar 

  31. Smith MA et al (2010) Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J Alzheimer’s Dis 19(1):353–372. https://doi.org/10.3233/JAD-2010-1239

    Article  CAS  Google Scholar 

  32. Carola V, D’Olimpio F, Brunamonti E, Mangia F, Renzi P (2002) Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav Brain Res 134(1–2):49–57. https://doi.org/10.1016/S0166-4328(01)00452-1

    Article  PubMed  Google Scholar 

  33. Durand M et al (1999) Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis in SHR and WKY rats. Neuropharmacology 38(6):893–907. https://doi.org/10.1016/S0028-3908(99)00009-X

    Article  CAS  PubMed  Google Scholar 

  34. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14(3):149–167. https://doi.org/10.1016/0165-0270(85)90031-7

    Article  CAS  PubMed  Google Scholar 

  35. Brown NS et al (2000) Thyroid hormone resistance and increased metabolic rate in the RXR-γ- deficient mouse. J Clin Invest 106(1):73–79. https://doi.org/10.1172/JCI9422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Porsolt RD (2000) Animal models of depression: utility for transgenic research. Rev Neurosci 11(1):53–58. https://doi.org/10.1515/REVNEURO.2000.11.1.53

    Article  CAS  PubMed  Google Scholar 

  37. Hughes RN (2004) The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neurosci Biobehav Rev 28(5):497–505. https://doi.org/10.1016/j.neubiorev.2004.06.006

    Article  CAS  PubMed  Google Scholar 

  38. Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11(1):47–60. https://doi.org/10.1016/0165-0270(84)90007-4

    Article  CAS  PubMed  Google Scholar 

  39. Kahloula K, Adli DEH, Slimani M, Terras H, Achour S (2014) Effet de l’exposition chronique au nickel sur les fonctions neurocomportementales chez les rats Wistar pendant la période de développement. Toxicol Anal Clin 26(4):186–192. https://doi.org/10.1016/j.toxac.2014.09.056

    Article  Google Scholar 

  40. Chao CC, Anderson WR, Hu S, Gekker G, Martella A, Peterson PK (1993) Activated microgila inhibit multiplication of toxoplasma gondii via a nitric oxide mechanism. Clin Immunol Immunopathol 67(2):178–183. https://doi.org/10.1006/clin.1993.1062

    Article  CAS  PubMed  Google Scholar 

  41. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 186:421–431. https://doi.org/10.1016/0076-6879(90)86135-I

    Article  CAS  PubMed  Google Scholar 

  42. Freitas RM, Sousa FCF, Vasconcelos SMM, Viana GSB, Fonteles MMF (2004) Pilocarpine-induced status epilepticus in rats: lipid peroxidation level, nitrite formation, GABAergic and glutamatergic receptor alterations in the hippocampus, striatum and frontal cortex. Pharmacol Biochem Behav 78(2):327–332. https://doi.org/10.1016/J.PBB.2004.04.004

    Article  CAS  PubMed  Google Scholar 

  43. Aebi H (1984) Catalase in vitro. Methods Enzymol. 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

    Article  CAS  PubMed  Google Scholar 

  44. Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92(2):180–185. https://doi.org/10.1007/BF00177912

    Article  CAS  PubMed  Google Scholar 

  45. Elferchichi M, Maaroufi K, Ammari M, Sakly M, Abdelmelek H (2015) Effects of combined ferrous sulfate administration and exposure to static magnetic field on brain oxidative stress and emotional behavior. Arch Ital Biol 153(1):37–45. https://doi.org/10.4449/aib.v153i1.1481

    Article  PubMed  Google Scholar 

  46. Chtourou Y, Ben Slima A, Gdoura R, Fetoui H (2015) Naringenin mitigates iron-induced anxiety-like behavioral impairment, mitochondrial dysfunctions, ectonucleotidases and acetylcholinesterase alteration activities in rat hippocampus. Neurochem Res 40(8):1563–1575. https://doi.org/10.1007/s11064-015-1627-9

    Article  CAS  PubMed  Google Scholar 

  47. Abel EL (1994) A further analysis of physiological changes in rats in the forced swim test. Physiol Behav 56(4):795–800. https://doi.org/10.1016/0031-9384(94)90245-3

    Article  CAS  PubMed  Google Scholar 

  48. Kim J, Wessling-Resnick M (2014) Iron and mechanisms of emotional behavior. J Nutr Biochem 25(11):1101–1107. https://doi.org/10.1016/j.jnutbio.2014.07.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sengstock GJ, Olanow CW, Dunn AJ, Barone S, Arendash GW (1994) Progressive changes in striatal dopaminergic markers, nigral volume, and rotational behavior following iron infusion into the rat substantia Nigra. Exp Neurol 130(1):82–94. https://doi.org/10.1006/exnr.1994.1187

    Article  CAS  PubMed  Google Scholar 

  50. Voigt JP, Rex A, Sohr R, Fink H (1999) Hippocampal 5-HT and NE release in the transgenic rat TGR(mREN2)27 related to behavior on the elevated plus maze. Eur Neuropsychopharmacol 9(4):279–285. https://doi.org/10.1016/S0924-977X(98)00031-5

    Article  CAS  PubMed  Google Scholar 

  51. Felt BT et al (2006) Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats. Behav Brain Res 171(2):261–270. https://doi.org/10.1016/j.bbr.2006.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Burhans MS, Dailey C, Wiesinger J, Murray-Kolb LE, Jones BC, Beard JL (2006) Iron deficiency affects acoustic startle response and latency, but not prepulse inhibition in young adult rats. Physiol Behav 87(5):917–924. https://doi.org/10.1016/j.physbeh.2006.02.014

    Article  CAS  PubMed  Google Scholar 

  53. Beard JL, Erikson KM, Jones BC (2002) Neurobehavioral analysis of developmental iron deficiency in rats. Behav Brain Res 134(1–2):517–524. https://doi.org/10.1016/S0166-4328(02)00092-X

    Article  CAS  PubMed  Google Scholar 

  54. Salvador GA, Uranga RM and Giusto NM (2011) Iron and mechanisms of neurotoxicity. Int J Alzheimers Dis 2011. https://doi.org/10.4061/2011/720658.

  55. Stankiewicz JM, Brass SD (2009) Role of iron in neurotoxicity: a cause for concern in the elderly? Curr Opin Clin Nutr Metab Care 12(1):22–29. https://doi.org/10.1097/MCO.0b013e32831ba07c

    Article  CAS  PubMed  Google Scholar 

  56. Squire LR (2004) Memory systems of the brain: a brief history and current perspective. Neurobiol Learn Mem 82(3):171–177. https://doi.org/10.1016/j.nlm.2004.06.005

    Article  PubMed  Google Scholar 

  57. Squire LR, Wixted JT, Clark RE (2007) Recognition memory and the medial temporal lobe: A new perspective. Nat Rev Neurosci 8(11):872–883. https://doi.org/10.1038/nrn2154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. De-Mello N, Souza-Junior IQ, Carobrez AP (2005) Pilocarpine prevents age-related spatial learning impairments in rats. Behav Brain Res 158(2):263–268. https://doi.org/10.1016/j.bbr.2004.09.006

    Article  CAS  PubMed  Google Scholar 

  59. Bohnen NI et al (2005) Cognitive correlates of alterations in acetylcholinesterase in Alzheimer’s disease. Neurosci Lett 380(1–2):127–132. https://doi.org/10.1016/j.neulet.2005.01.031

    Article  CAS  PubMed  Google Scholar 

  60. Rouault TA, Cooperman S (2006) Brain iron metabolism. Semin Pediatr Neurolog 13(3):142–148. https://doi.org/10.1016/j.spen.2006.08.002

    Article  Google Scholar 

  61. Ben-Shachar D, Youdim MBH (1991) Intranigral iron injection induces behavioral and biochemical ‘Parkinsonism’ in rats. J Neurochem 57(6):2133–2135. https://doi.org/10.1111/j.1471-4159.1991.tb06432.x

    Article  CAS  PubMed  Google Scholar 

  62. Sengstock GJ, Olanow CW, Menzies RA, Dunn AJ, Arendash GW (1993) Infusion of iron into the rat substantia nigra: nigral pathology and dose-dependent loss of striatal dopaminergic markers. J Neurosci Res 35(1):67–82. https://doi.org/10.1002/jnr.490350109

    Article  CAS  PubMed  Google Scholar 

  63. Viktorinova A (2018) Iron-mediated oxidative cell death is a potential contributor to neuronal dysfunction induced by neonatal hemolytic hyperbilirubinemia. Arch Biochem Biophys 654(April):185–193. https://doi.org/10.1016/j.abb.2018.07.022

    Article  CAS  PubMed  Google Scholar 

  64. Budni P, De Lima MNM, Polydoro M, Moreira JCF, Schroder N, Dal-Pizzol F (2007) Antioxidant effects of selegiline in oxidative stress induced by iron neonatal treatment in rats. Neurochem Res 32(6):965–972. https://doi.org/10.1007/s11064-006-9249-x

    Article  CAS  PubMed  Google Scholar 

  65. Glei DA, Goldman N, Chuang YL, Weinstein M (2007) Do chronic stressors lead to physiological dysregulation? Testing the theory of allostatic load. Psychosom Med 69(8):769–776. https://doi.org/10.1097/PSY.0b013e318157cba6

    Article  PubMed  Google Scholar 

  66. Chiueh CC (2001) Iron overload, oxidative stress, and axonal dystrophy in brain disorders. Pediatr Neurol 25(2):138–147. https://doi.org/10.1016/S0887-8994(01)00266-1

    Article  CAS  PubMed  Google Scholar 

  67. Dhakshinamoorthy V, Manickam V, Perumal E (2017) Neurobehavioural toxicity of iron oxide nanoparticles in mice. Neurotox Res 32(2):187–203. https://doi.org/10.1007/s12640-017-9721-1

    Article  CAS  PubMed  Google Scholar 

  68. Kokoszko A, Dabrowski J, Lewiński A, Karbownik-Lewińska M (2008) Protective effects of GH and IGF-I against iron-induced lipid peroxidation in vivo. Exp Toxicol Pathol 60(6):453–458. https://doi.org/10.1016/j.etp.2008.04.012

    Article  CAS  PubMed  Google Scholar 

  69. Valko M, Morris H, Cronin M (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208. https://doi.org/10.2174/0929867053764635

    Article  CAS  PubMed  Google Scholar 

  70. Dal-Pizzol F et al (2001) Neonatal iron exposure induces oxidative stress in adult Wistar rat. Dev Brain Res 130(1):109–114. https://doi.org/10.1016/S0165-3806(01)00218-8

    Article  CAS  Google Scholar 

  71. Gutteridge JMC, Halliwell B (2000) Free radicals and antioxidants in the year 2000. A historical look to the future. Ann NY Acad Sci 899:136–147. https://doi.org/10.1111/J.1749-6632.2000.TB06182.X

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Rezqaoui Ayoub and Ibouzine-dineLaila. The first draft of the manuscript was written by Reqaoui Ayoub and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ayoub Rezqaoui.

Ethics declarations

Ethics Approval and Consent to Participate

All animal experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Animal Ethics Committee (Local Institutional Research Committee).

Competing Interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rezqaoui, A., Ibouzine-dine, L., Elhamzaoui, A. et al. Potential Role of Oxidative Stress in the Effects of Chronic Administration of Iron on Affective and Cognitive Behavior on Male Wistar Rat. Biol Trace Elem Res 201, 4812–4826 (2023). https://doi.org/10.1007/s12011-023-03560-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-023-03560-z

Keywords

Navigation