title: Manganese leads to an increase in markers of oxidative stress as well as to a shift in the ratio of Fe(II)/(III) in rat brain tissue.
abstract: Occupationally or environmentally caused chronic exposure to Manganese (Mn) can lead to a degeneration of dopaminergic neurons inducing a Parkinson-like complaint called manganism. Deciphering the ongoing neurodegenerative mechanisms in the affected brain is still a major task for understanding the complex modes of action. Therefore, we applied a non-toxic, oral feeding in rats simulating a chronic exposure to Mn. Analysis of brain extracts by electrospray ionization Fourier transform resonance mass spectrometry (ESI-FT-ICR-MS) revealed an increase in markers of oxidative stress like glutathione disulfide (GSSG), prostaglandins, and 15(S)-HETE, a marker of lipid peroxidation. Furthermore, acetylcholinesterase (AchE) activity and glutamate concentrations were elevated in brain samples of Mn-supplemented rats, suggesting oxidative stress in the brain tissue. Application of ion chromatography coupled to inductively coupled plasma-optical emission spectrometry (IC-ICP-OES) further showed a shift of Fe(III) towards Fe(II) in the brain samples enabling for example the action of the Fenton reaction. This is the first time that changes in the Fe-species distribution could be related to Mn-induced neuroinflammation and is therefore enlarging the knowledge of this complex neurodegenerative condition. The combination of our findings provides substantial evidence that Mn-induced neuroinflammation leads to oxidative stress triggered by multifactorial pathophysiological processes.
authors.affiliation: Research Unit Analytical Biogeochemistry, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany. Katharina.Fernsebner@helmholtz-muenchen.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fernsebner
authors.forename: Julia
authors.initials: J
authors.lastname: Zorn
authors.forename: Basem
authors.initials: B
authors.lastname: Kanawati
authors.forename: Alesia
authors.initials: A
authors.lastname: Walker
authors.forename: Bernhard
authors.initials: B
authors.lastname: Michalke
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D004435:Eating; D005290:Ferric Compounds / Q000032:analysis / Q000378:metabolism*; D005296:Ferrous Compounds / Q000032:analysis / Q000378:metabolism*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D018698:Glutamic Acid; D008345:Manganese