title: An approach for manganese biomonitoring using a manganese carrier switch in serum from transferrin to citrate at slightly elevated manganese concentration.
abstract: After high-dose-short-term exposure (usually from occupational exposure) and even more under low-dose long term exposure (mainly environmental) manganese (Mn) biomonitoring is still problematic since these exposure scenarios are not necessarily reflected by a significant increase of total Mn in blood or serum. Usually, Mn concentrations of exposed and unexposed persons overlap and individual differentiation is often not possible. In this paper Mn speciation on a large sample size (n=180) was used in order to be able to differentiate between highly Mn-exposed or low or unexposed individuals at low total Mn concentration in serum (Mn(S)). The whole sample set consisted of three subsets from Munich, Emilia Romagna region in Italy and from Sweden. It turned out that also at low total Mn(S) concentrations a change in major Mn carriers in serum takes place from Mn-transferrin (Mn-Tf(S)) towards Mn-citrate (Mn-Cit(S)) with high statistical significance (p<0.000002). This carrier switch from Mn-Tf(S) to Mn-Cit(S) was observed between Mn(S) concentrations of 1.5μg/L to ca. 1.7μg/L. Parallel to this carrier change, for sample donors from Munich where serum and cerebrospinal fluid were available, the concentration of Mn beyond neural barriers - analysed as Mn in cerebrospinal fluid (Mn(C)) - positively correlates to Mn-Cit(S) when Mn(S) concentration was above 1.7μg/L. The correlation between Mn-Cit(S) and Mn(C) reflects the facilitated Mn transport through neural barrier by means of Mn-citrate. Regional differences in switch points from Mn-Tf(S) to Mn-Cit(S) were observed for the three sample subsets. It is currently unknown whether these differences are due to differences in location, occupation, health status or other aspects. Based on our results, Mn-Cit(S) determination was considered as a potential means for estimating the Mn load in brain and CSF, i.e., it could be used as a biomarker for Mn beyond neural barrier. For a simpler Mn-Cit(S) determination than size exclusion chromatography inductively coupled plasma mass spectrometry (SEC-ICP-MS), ultrafiltration (UF) of serum samples was tested for suitability, the latter possibly being a preferred choice for routine occupational medicine laboratories. Our results revealed that UF could be an alternative if methodical prerequisites and limitations are carefully considered. These prerequisites were determined to be a thorough cleaning procedure at a minimum Mn(S) concentration >1.5μg/L, as at lower concentrations a wide scattering of the measured concentrations in comparison to the standardized SEC-ICP-MS results were observed.
authors: Research Unit Analytical BioGeoChemistry, Helmholtz Center Munich - German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany. Electronic address: bernhard.michalke@helmholtz-muenchen.de.
authors: B
authors: B
authors: Michalke
authors: Research Unit Analytical BioGeoChemistry, Helmholtz Center Munich - German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany; School of Chemical Engineering, Laboratory of Inorganic and Analytical Chemistry, National Technical University of Athens, Greece.
authors: L
authors: L
authors: Aslanoglou
authors: School of Chemical Engineering, Laboratory of Inorganic and Analytical Chemistry, National Technical University of Athens, Greece.
authors: M
authors: M
authors: Ochsenkühn-Petropoulou
authors: Örebro University Hospital, Department of Occupational and Environmental Medicine, SE-70185 Örebro, Sweden.
authors: B
authors: B
authors: Bergström
authors: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
authors: A
authors: A
authors: Berthele
authors: CREAGEN - Environmental, Genetic and Nutritional Epidemiology Research Center, University of Modena and Reggio Emilia, Modena, Italy.
authors: M
authors: M
authors: Vinceti
authors: Research Unit Analytical BioGeoChemistry, Helmholtz Center Munich - German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
authors: M
authors: M
authors: Lucio
authors: Department of Analytical Chemistry and Environmental Science, Atmospheric Science Unit, Stockholm University, SE-106 90 Stockholm, Sweden.
authors: G
authors: G
authors: Lidén
mesh_terms: D019343:Citric Acid / Q000097:blood*; D004784:Environmental Monitoring; D006801:Humans; D016014:Linear Models; D008345:Manganese / Q000097:blood*; D011786:Quality Control; D012996:Solutions; D014168:Transferrin / Q000378:metabolism*; D014462:Ultrafiltration
chemical_list: D012996:Solutions; D014168:Transferrin; D019343:Citric Acid; D008345:Manganese
keywords: Biomonitoring; Manganese speciation; Mn-carrier switch; Mn-citrate; Size exclusion chromatography inductively coupled plasma mass spectrometry; Ultrafiltration