TY  - JOUR
A1  - Lohren, Hanna
A1  - Blagojevic, Lara
A1  - Fitkau, Romy
A1  - Ebert, Franziska
A1  - Schildknecht, Stefan
A1  - Leist, Marcel
A1  - Schwerdtle, Tanja
T1  - Toxicity of organic and inorganic mercury species in human neurons and human astrocytes
JF  - Journal of trace elements in medicine and biology
N2  - Organic mercury (Hg) species exert their toxicity primarily in the central nervous system. The food relevant Hg species methylmercury (MeHg) has been frequently studied regarding its neurotoxic effects in vitro and in vivo. Neurotoxicity of thiomersal, which is used as a preservative in medical preparations, is to date less characterised. Due to dealkylation of organic Hg or oxidation of elemental Hg, inorganic Hg is present in the brain albeit these species are not able to readily cross the blood brain barrier. This study compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and thiomersal as well as inorganic mercury chloride (HgCl2) in differentiated human neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in their degree and mechanism of toxicity in those two types of brain cells. Generally, neurons are more susceptible to Hg species induced cytotoxicity as compared to astrocytes. This might be due to the massive cellular mercury uptake in the differentiated neurons. The organic compounds exerted stronger cytotoxic effects as compared to inorganic HgCl2. In contrast to HgCl2 exposure, organic Hg compounds seem to induce the apoptotic cascade in neurons following low-level exposure. No indicators for apoptosis were identified for both inorganic and organic mercury species in astrocytes. Our studies clearly demonstrate species-specific toxic mechanisms. A mixed exposure towards all Hg species in the brain can be assumed. Thus, prospectively coexposure studies as well as cocultures of neurons and astrocytes could provide additional information in the investigation of Hg induced neurotoxicity.
KW  - Methylmercury
KW  - Thiomersal
KW  - Mercuric mercury
KW  - Human differentiated neurons
KW  - Cytotoxicity
KW  - Apoptosis
Y1  - 2015
U6  - https://doi.org/10.1016/j.jtemb.2015.06.008
SN  - 0946-672X
VL  - 32
SP  - 200
EP  - 208
PB  - Elsevier
CY  - Jena
ER  - 
TY  - JOUR
A1  - Lohren, Hanna
A1  - Bornhorst, Julia
A1  - Fitkau, Romy
A1  - Pohl, Gabriele
A1  - Galla, Hans-Joachim
A1  - Schwerdtle, Tanja
T1  - Effects on and transfer across the blood-brain barrier in vitro-Comparison of organic and inorganic mercury species
JF  - BMC pharmacology & toxicology
N2  - Background: Transport of methylmercury (MeHg) across the blood-brain barrier towards the brain side is well discussed in literature, while ethylmercury (EtHg) and inorganic mercury are not adequately characterized regarding their entry into the brain. Studies investigating a possible efflux out of the brain are not described to our knowledge. Methods: This study compares, for the first time, effects of organic methylmercury chloride (MeHgCl), EtHg-containing thiomersal and inorganic Hg chloride (HgCl2) on as well as their transfer across a primary porcine in vitro model of the blood-brain barrier. Results: With respect to the barrier integrity, the barrier model exhibited a much higher sensitivity towards HgCl2 following basolateral incubation (brain-facing side) as compared to apical application (blood-facing side). These HgCl2 induced effects on the barrier integrity after brain side incubation are comparable to that of the organic species, although MeHgCl and thiomersal exerted much higher cytotoxic effects in the barrier building cells. Hg transfer rates following exposure to organic species in both directions argue for diffusion as transfer mechanism. Inorganic Hg application surprisingly resulted in a Hg transfer out of the brain-facing compartment. Conclusions: In case of MeHgCl and thiomersal incubation, mercury crossed the barrier in both directions, with a slight accumulation in the basolateral, brain-facing compartment, after simultaneous incubation in both compartments. For HgCl2, our data provide first evidence that the blood-brain barrier transfers mercury out of the brain.
KW  - Organic mercury
KW  - Inorganic mercury
KW  - Methylmercury
KW  - Thiomersal
KW  - Mercuric mercury
KW  - In vitro blood-brain barrier model
Y1  - 2016
U6  - https://doi.org/10.1186/s40360-016-0106-5
SN  - 2050-6511
VL  - 17
SP  - 422
EP  - 433
PB  - BioMed Central
CY  - London
ER  -