TY - JOUR A1 - Witt, Barbara A1 - Stiboller, Michael A1 - Raschke, Stefanie A1 - Friese, Sharleen A1 - Ebert, Franziska A1 - Schwerdtle, Tanja T1 - Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers JF - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS N2 - Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases. KW - Copper KW - Astrocytes KW - Toxicity KW - Mitochondria KW - ROS KW - Trace elements Y1 - 2021 U6 - https://doi.org/10.1016/j.jtemb.2021.126711 SN - 1878-3252 VL - 65 PB - Elsevier CY - München ER - TY - JOUR A1 - Lechleitner, Franziska A. A1 - Baldini, James U. L. A1 - Breitenbach, Sebastian Franz Martin A1 - Fohlmeister, Jens Bernd A1 - McIntyre, Cameron A1 - Goswami, Bedartha A1 - Jamieson, Robert A. A1 - van der Voort, Tessa S. A1 - Prufer, Keith A1 - Marwan, Norbert A1 - Culleton, Brendan J. A1 - Kennett, Douglas J. A1 - Asmerom, Yemane A1 - Polyak, Victor A1 - Eglinton, Timothy I. T1 - Hydrological and climatological controls on radiocarbon concentrations in a tropical stalagmite JF - Geochimica et cosmochimica acta : journal of the Geochemical Society and the Meteoritical Society N2 - Precisely-dated stalagmites are increasingly important archives for the reconstruction of terrestrial paleoclimate at very high temporal resolution. In-depth understanding of local conditions at the cave site and of the processes driving stalagmite deposition is of paramount importance for interpreting proxy signals incorporated in stalagmite carbonate. Here we present a sub-decadally resolved dead carbon fraction (DCF) record for a stalagmite from Yok Balum Cave (southern Belize). The record is coupled to parallel stable carbon isotope (delta C-13) and U/Ca measurements, as well as radiocarbon (C-14) measurements from soils overlying the cave system. Using a karst carbon cycle model we disentangle the importance of soil and karst processes on stalagmite DCF incorporation, revealing a dominant host rock dissolution control on total DCF. Covariation between DCF, delta C-13, and U/Ca indicates that karst processes are a common driver of all three parameters, suggesting possible use of delta C-13 and trace element ratios to independently quantify DCF variability. A statistically significant multi-decadal lag of variable length exists between DCF and reconstructed solar activity, suggesting that solar activity influenced regional precipitation in Mesoamerica over the past 1500 years, but that the relationship was non-static. Although the precise nature of the observed lag is unclear, solar-induced changes in North Atlantic oceanic and atmospheric dynamics may play a role. (C) 2016 Elsevier Ltd. All rights reserved. KW - Stalagmite KW - Tropics KW - Radiocarbon KW - Trace elements KW - Hydroclimate Y1 - 2016 U6 - https://doi.org/10.1016/j.gca.2016.08.039 SN - 0016-7037 SN - 1872-9533 VL - 194 SP - 233 EP - 252 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Drobyshev, Evgenii J. A1 - Solovyev, Nikolay D. A1 - Gorokhovskiy, Boris M. A1 - Kashuro, Vadim A. T1 - Accumulation Patterns of Sub-chronic Aluminum Toxicity Model After Gastrointestinal Administration in Rats JF - Biological Trace Element Research N2 - Although aluminum chronic neurotoxicity is well documented, there are no well-established experimental protocols of Al exposure. In the current study, toxic effects of sub-chronic Al exposure have been evaluated in outbreed male rats (gastrointestinal administration). Forty animals were used: 10 were administered with AlCl3 water solution (2 mg/kg Al per day) for 1 month, 10 received the same concentration of AlCl3 for 3 month, and 20 (10 per observation period) saline as control. After 30 and 90 days, the animals underwent behavioral tests: open field, passive avoidance, extrapolation escape task, and grip strength. At the end of the study, the blood, liver, kidney, and brain were excised for analytical and morphological studies. The Al content was measured by inductively coupled plasma mass-spectrometry. Essential trace elements-Co, Cr, Cu, Fe, Mg, Mn, Mo, Se, and Zn-were measured in whole blood samples. Although no morphological changes were observed in the brain, liver, or kidney for both exposure terms, dose-dependent Al accumulation and behavioral differences (increased locomotor activity after 30 days) between treatment and control groups were indicated. Moreover, for 30 days exposure, strong positive correlation between Al content in the brain and blood for individual animals was established, which surprisingly disappeared by the third month. This may indicate neural barrier adaptation to the Al exposure or the saturation of Al transport into the brain. Notably, we could not see a clear neurodegeneration process after rather prolonged sub-chronic Al exposure, so probably longer exposure periods are required. KW - Aluminum KW - Neurotoxicity KW - Rats KW - Per oral administration KW - Sub-chronic exposure KW - Trace elements Y1 - 2018 U6 - https://doi.org/10.1007/s12011-018-1247-8 SN - 0163-4984 SN - 1559-0720 VL - 185 IS - 2 SP - 384 EP - 394 PB - Humana Press Inc. CY - Totowa ER - TY - JOUR A1 - Bornhorst, Julia A1 - Kipp, Anna P. A1 - Haase, Hajo A1 - Meyer, Soeren A1 - Schwerdtle, Tanja T1 - The crux of inept biomarkers for risks and benefits of trace elements JF - Trends in Analytical Chemistry N2 - Nowadays, the role of trace elements (TE) is of growing interest because dyshomeostasis of selenium (Se), manganese (Mn), zinc (Zn), and copper (Cu) is supposed to be a risk factor for several diseases. Thereby, research focuses on identifying new biomarkers for the TE status to allow for a more reliable description of the individual TE and health status. This review mirrors a lack of well-defined, sensitive, and selective biomarkers and summarizes technical limitations to measure them. Thus, the capacity to assess the relationship between dietary TE intake, homeostasis, and health is restricted, which would otherwise provide the basis to define adequate intake levels of single TE in both healthy and diseased humans. Besides that, our knowledge is even more limited with respect to the real life situation of combined TE intake and putative interactions between single TE. KW - Trace elements KW - Copper KW - Zinc KW - Manganese KW - Selenium KW - Biomarker KW - Inductively coupled plasma mass spectrometry KW - Hyphenated techniques KW - Isotope ratios Y1 - 2018 U6 - https://doi.org/10.1016/j.trac.2017.11.007 SN - 0165-9936 SN - 1879-3142 VL - 104 SP - 183 EP - 190 PB - Elsevier CY - Oxford ER -