The Effect of High Dose Oral Manganese Exposure on Copper, Iron and Zinc Levels in Rats

Overview

Journal Biometals

Specialty Biochemistry

Date 2016 Mar 19

PMID 26988220

Citations 10

Authors

Courtney J Mercadante

Carolina Herrera

Michael A Pettiglio

Melanie L Foster

Laura C Johnson

David C Dorman

Thomas B Bartnikas

Affiliations

Soon will be listed here.

Abstract

Manganese is an essential dietary nutrient and trace element with important roles in mammalian development, metabolism, and antioxidant defense. In healthy individuals, gastrointestinal absorption and hepatobiliary excretion are tightly regulated to maintain systemic manganese concentrations at physiologic levels. Interactions of manganese with other essential metals following high dose ingestion are incompletely understood. We previously reported that gavage manganese exposure in rats resulted in higher tissue manganese concentrations when compared with equivalent dietary or drinking water manganese exposures. In this study, we performed follow-up evaluations to determine whether oral manganese exposure perturbs iron, copper, or zinc tissue concentrations. Rats were exposed to a control diet with 10 ppm manganese or dietary, drinking water, or gavage exposure to approximately 11.1 mg manganese/kg body weight/day for 7 or 61 exposure days. While manganese exposure affected levels of all metals, particularly in the frontal cortex and liver, copper levels were most prominently affected. This result suggests an under-appreciated effect of manganese exposure on copper homeostasis which may contribute to our understanding of the pathophysiology of manganese toxicity.

Citing Articles

Sex-specific associations between co-exposure to multiple metals and externalizing symptoms in adolescence and young adulthood.

Oluyemi K, Rechtman E, Invernizzi A, Gennings C, Renzetti S, Patrono A Environ Res. 2024; 250:118443.

PMID: 38365053 PMC: 11102844. DOI: 10.1016/j.envres.2024.118443.

Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents.

Invernizzi A, Rechtman E, Oluyemi K, Renzetti S, Curtin P, Colicino E Front Neurosci. 2023; 17:1098441.

PMID: 36814793 PMC: 9939635. DOI: 10.3389/fnins.2023.1098441.

Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model.

Areecheewakul S, Adamcakova-Dodd A, Haque E, Jing X, Meyerholz D, OShaughnessy P Part Fibre Toxicol. 2022; 19(1):40.

PMID: 35698146 PMC: 9195454. DOI: 10.1186/s12989-022-00480-z.

Determining the effects of manganese source and level on growth performance and carcass characteristics of growing-finishing pigs.

Kerkaert H, Woodworth J, DeRouchey J, Dritz S, Tokach M, Goodband R Transl Anim Sci. 2021; 5(2):txab067.

PMID: 34386713 PMC: 8355436. DOI: 10.1093/tas/txab067.

Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis.

Baesler J, Michaelis V, Stiboller M, Haase H, Aschner M, Schwerdtle T Mol Nutr Food Res. 2021; 65(8):e2001176.

PMID: 33641237 PMC: 8224813. DOI: 10.1002/mnfr.202001176.

References

Tarohda T, Ishida Y, Kawai K, Yamamoto M, Amano R . Regional distributions of manganese, iron, copper, and zinc in the brains of 6-hydroxydopamine-induced parkinsonian rats. Anal Bioanal Chem. 2005; 383(2):224-34. DOI: 10.1007/s00216-005-3423-x. View

Ehrnstorfer I, Geertsma E, Pardon E, Steyaert J, Dutzler R . Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport. Nat Struct Mol Biol. 2014; 21(11):990-6. DOI: 10.1038/nsmb.2904. View

Mullin E, Wegst-Uhrich S, Ding D, Manohar S, Muthaiah V, Salvi R . Effect of manganese treatment on the accumulation on biologically relevant metals in rat cochlea and brain by inductively coupled plasma mass spectrometry. Biometals. 2015; 28(6):1009-16. DOI: 10.1007/s10534-015-9885-1. View

Butterworth R . Metal toxicity, liver disease and neurodegeneration. Neurotox Res. 2010; 18(1):100-5. DOI: 10.1007/s12640-010-9185-z. View

Bouchard M, Sauve S, Barbeau B, Legrand M, Brodeur M, Bouffard T . Intellectual impairment in school-age children exposed to manganese from drinking water. Environ Health Perspect. 2010; 119(1):138-43. PMC: 3018493. DOI: 10.1289/ehp.1002321. View

Zheng G, Chen J, Zheng W . Relative contribution of CTR1 and DMT1 in copper transport by the blood-CSF barrier: implication in manganese-induced neurotoxicity. Toxicol Appl Pharmacol. 2012; 260(3):285-93. PMC: 3336026. DOI: 10.1016/j.taap.2012.03.006. View

Moldovan N, Al-Ebraheem A, Miksys N, Farquharson M, Bock N . Altered transition metal homeostasis in mice following manganese injections for manganese-enhanced magnetic resonance imaging. Biometals. 2013; 26(1):179-87. DOI: 10.1007/s10534-012-9605-z. View

Salvador G, Uranga R, Giusto N . Iron and mechanisms of neurotoxicity. Int J Alzheimers Dis. 2011; 2011:720658. PMC: 3014724. DOI: 10.4061/2011/720658. View

Fitsanakis V, Zhang N, Avison M, Gore J, Aschner J, Aschner M . The use of magnetic resonance imaging (MRI) in the study of manganese neurotoxicity. Neurotoxicology. 2006; 27(5):798-806. DOI: 10.1016/j.neuro.2006.03.001. View

10.

Guilarte T, Burton N, Verina T, Prabhu V, Becker K, Syversen T . Increased APLP1 expression and neurodegeneration in the frontal cortex of manganese-exposed non-human primates. J Neurochem. 2008; 105(5):1948-59. PMC: 4335763. DOI: 10.1111/j.1471-4159.2008.05295.x. View

11.

Verina T, Schneider J, Guilarte T . Manganese exposure induces α-synuclein aggregation in the frontal cortex of non-human primates. Toxicol Lett. 2012; 217(3):177-83. PMC: 3638947. DOI: 10.1016/j.toxlet.2012.12.006. View

12.

Borras M . Hormone dependency of splenic iron stores in the rat: effect of oestrogens on the recuperation of reserves in ferrodeficient subjects. Lab Anim. 1998; 32(3):290-7. DOI: 10.1258/002367798780559275. View

13.

Oulhote Y, Mergler D, Barbeau B, Bellinger D, Bouffard T, Brodeur M . Neurobehavioral function in school-age children exposed to manganese in drinking water. Environ Health Perspect. 2014; 122(12):1343-50. PMC: 4256698. DOI: 10.1289/ehp.1307918. View

14.

Fu X, Zhang Y, Jiang W, Monnot A, Bates C, Zheng W . Regulation of copper transport crossing brain barrier systems by Cu-ATPases: effect of manganese exposure. Toxicol Sci. 2014; 139(2):432-51. PMC: 4064014. DOI: 10.1093/toxsci/kfu048. View

15.

Wasserman G, Liu X, Parvez F, Ahsan H, Levy D, Factor-Litvak P . Water manganese exposure and children's intellectual function in Araihazar, Bangladesh. Environ Health Perspect. 2006; 114(1):124-9. PMC: 1332667. DOI: 10.1289/ehp.8030. View

16.

Dusek P, Roos P, Litwin T, Schneider S, Flaten T, Aaseth J . The neurotoxicity of iron, copper and manganese in Parkinson's and Wilson's diseases. J Trace Elem Med Biol. 2014; 31:193-203. DOI: 10.1016/j.jtemb.2014.05.007. View

17.

Foster M, Bartnikas T, Johnson L, Herrera C, Pettiglio M, Keene A . Pharmacokinetic evaluation of the equivalency of gavage, dietary, and drinking water exposure to manganese in F344 rats. Toxicol Sci. 2015; 145(2):244-51. PMC: 4490190. DOI: 10.1093/toxsci/kfv047. View

18.

Racette B . Manganism in the 21st century: the Hanninen lecture. Neurotoxicology. 2013; 45:201-7. PMC: 3992192. DOI: 10.1016/j.neuro.2013.09.007. View

19.

Woolf A, Wright R, Amarasiriwardena C, Bellinger D . A child with chronic manganese exposure from drinking water. Environ Health Perspect. 2002; 110(6):613-6. PMC: 1240879. DOI: 10.1289/ehp.02110613. View

20.

Nong A, Taylor M, Clewell 3rd H, Dorman D, Andersen M . Manganese tissue dosimetry in rats and monkeys: accounting for dietary and inhaled Mn with physiologically based pharmacokinetic modeling. Toxicol Sci. 2008; 108(1):22-34. DOI: 10.1093/toxsci/kfn264. View