Manganese and iron species in Sprague–Dawley rats exposed with MnCl2∙4H2O (i.v.)

Diederich, J.; Brielmeier, Markus; Schwerdtle, Tanja; Michalke, Bernhard

doi:10.1016/j.microc.2012.03.015

Cited by 10 publications

(5 citation statements)

References 52 publications

(91 reference statements)

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“…Interestingly, in serum, we observed major effects for Mn-species formation for fractions C and E after this short exposure [ 26 ]. For transportation across neural barriers, also Mn-citrate (fraction D) seemed to be important, which is in line with previous speciation studies, where an active transport of LMM Mn-species across neural barriers was hypothesized [ 19 , 20 , 27 , 28 ]. So far it is assumed that preliminary Mn-citrate is formed during Mn exposure at certain concentrations.…”

Section: Resultssupporting

confidence: 88%

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Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats

et al. 2015

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Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography—inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization—ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism.

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Section: Resultssupporting

confidence: 88%

“…In a previous study, Diederich et al applied a single low dose Mn injection (1 mg/kg b.w., i.v. ), which revealed that, besides inorganic Mn, Mn-citrate was the predominant Mn-species in rat brain extracts of exposed animals [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats

et al. 2015

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“…This was also observed by Yokel and Crossgrove as well as by Nischwitz et al, who investigated the permeability of the BCB by means of Mn-speciation . All in all, there are indices for a carrier-mediated uptake of LMM Mn compounds (especially Mn-citrate), which is believed to lead to Mn accumulation in the brain . The results obtained herein for Mn-species in serum might enlarge these different studies on Mn-speciation.…”

Section: Results and Discussionmentioning

confidence: 60%

“…29 All in all, there are indices for a carrier-mediated uptake of LMM Mn compounds (especially Mn-citrate), which is believed to lead to Mn accumulation in the brain. 30 The results obtained herein for Mn-species in serum might enlarge these different studies on Mn-speciation. For an analysis of differences in SEC-fractions, partial leastsquare means were calculated after log transformation, and differences were calculated after Tukey−Kramer adjustment.…”

Section: Chemical Research In Toxicologymentioning

confidence: 99%

“…However, 1 h after Mn-injection transferrin showed a strong significant increase and still was significantly increased 4 days after injection when compared to that of the control (Figure 2). Hence, it seems as if transferrin is a first response for transportation of Mn after acute exposure 30 and passes this task to other serum compounds after a prolonged exposure, where other transporters like citrate become more important. Regarding the HMM fractions A and B, no significant differences between control and Mn-exposed groups were observed during subchronic feeding or 4 days after the injection of Mn.…”

Section: Chemical Research In Toxicologymentioning

confidence: 99%

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Diverse Serum Manganese Species Affect Brain Metabolites Depending on Exposure Conditions

Neth¹,

Lucio²,

Walker³

et al. 2015

Chem. Res. Toxicol.

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Occupational and environmental exposure to increased concentrations of manganese (Mn) can lead to an accumulation of this element in the brain. The consequence is an irreversible damage of dopaminergic neurons leading to a disease called manganism with a clinical presentation similar to the one observed in Parkinson's disease. Human as well as animal studies indicate that Mn is mainly bound to low molecular mass (LMM) compounds such as Mn-citrate when crossing neural barriers. The shift toward LMM compounds might already take place in serum due to elevated Mn concentrations in the body. In this study, we investigated Mn-species pattern in serum in two different animal models by size exclusion chromatography-inductively coupled plasma mass spectrometry (SEC-ICP-MS). A subchronic feeding of rats with elevated levels of Mn led to an increase in LMM compounds, mainly Mn-citrate and Mn bound to amino acids. In addition, a single i.v. injection of Mn showed an increase in Mn-transferrin and Mn bound to amino acids 1 h after injection, while species values were more or less rebalanced 4 days after the injection. Results from Mn-speciation were correlated to the brain metabolome determined by means of electrospray ionization ion cyclotron resonance Fourier transform mass spectrometry (ESI-ICR/FT-MS). The powerful combination of Mn-speciation in serum with metabolomics of the brain underlined the need for Mn-speciation in exposure scenarios instead of the determination of whole Mn concentrations in blood. The progress of Mn-induced neuronal injury might therefore be assessed on the basis of known serum Mn-species.

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Biomedical and Pharmaceutical Applications

et al. 2016

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Manganese and iron species in Sprague–Dawley rats exposed with MnCl2∙4H2O (i.v.)

Cited by 10 publications

References 52 publications

Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats

Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats

Diverse Serum Manganese Species Affect Brain Metabolites Depending on Exposure Conditions

Biomedical and Pharmaceutical Applications

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