scholarly journals Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

2019 ◽  
Vol 94 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Sam Kacew ◽  
A. Wallace Hayes

AbstractTetrabromobisphenol A (2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol, CAS no. 79-94-7) (TBBPA) is an effective brominated flame retardant present in many consumer products whose effectiveness is attributable to its ability to retard flames and consequently save human lives. Toxicokinetic studies revealed that TBBPA when absorbed via the gastrointestinal tract is rapidly metabolized to glucuronide or sulfate metabolites which are rapidly eliminated by the kidney. TBBPA does not accumulate in the body and there is no evidence that the parent compound is present in the brain. Although this brominated flame retardant was detected in human breast milk and serum, there was no evidence that TBBPA reached the brain in in vivo animal studies as reflected by the absence of neuropathological, neurotoxic, or behavioral alterations indicating that the central nervous system is not a target tissue. These animal investigations were further supported by use of the larval/embryo observations that TBBPA did not produce behavioral changes in a larval/embryo zebrafish a model of chemical-induced neurotoxicity. Although some protein expressions were increased, deceased or not affected in the blood–brain barrier indicating no evidence that TBBPA entered the brain, the changes were contradictory, or gender related, and behavior was not affected supporting that this compound was not neurotoxic. Taken together, TBBPA does not appear to target the brain and is not considered as a neurotoxicant.

Chemosphere ◽  
2011 ◽  
Vol 85 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Timothée Debenest ◽  
Anne-Nöelle Petit ◽  
François Gagné ◽  
Mohan Kohli ◽  
Nien Nguyen ◽  
...  

2006 ◽  
Vol 44 (8) ◽  
pp. 1408-1413 ◽  
Author(s):  
Y. Tada ◽  
T. Fujitani ◽  
N. Yano ◽  
H. Takahashi ◽  
K. Yuzawa ◽  
...  

2013 ◽  
Vol 304 (3) ◽  
pp. C240-C247 ◽  
Author(s):  
Amy S. Yu ◽  
Bruce A. Hirayama ◽  
Gerald Timbol ◽  
Jie Liu ◽  
Ana Diez-Sampedro ◽  
...  

Na+-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood-brain barrier (BBB), in vivo delivery of the probe into the brain was achieved after opening of the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum, hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex, and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia prompt the speculation that SGLTs may play an essential role in glucose utilization under stress such as ischemia. The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes.


2018 ◽  
Vol 27 (8) ◽  
pp. 1203-1209
Author(s):  
Bok-Nam Park ◽  
Tae Sung Lim ◽  
Joon-Kee Yoon ◽  
Young-Sil An

Purpose: The purpose of this study was to investigate how intravenously injected bone marrow-derived mesenchymal stem cells (BMSCs) are distributed in the body of an Alzheimer’s disease (AD) animal model. Methods: Stem cells were collected from bone marrow of mice and labeled with Indium-111 (111In). The 111In-labeled BMSCs were infused intravenously into 3×Tg-AD mice in the AD group and non-transgenic mice (B6129SF2/J) as controls. Biodistribution was evaluated with a gamma counter and gamma camera 24 and 48 h after injecting the stem cells. Results: A gamma count of the brain showed a higher distribution of labeled cells in the AD model than in the control group at 24 (p = .0004) and 48 h (p = .0016) after injection of the BMSCs. Similar results were observed by gamma camera imaging (i.e., brain uptake in the AD model was significantly higher than that in the control group). Among the other organs, uptake by the spleen was the highest in both groups. More BMSCs were found in the lungs of the control group than in those of the AD group. Conclusions: These results suggest that more intravenously infused BMSCs reached the brain in the AD model than in the control group, but the numbers of stem cells reaching the brain was very small.


2019 ◽  
Vol 6 (3) ◽  
pp. 970-980 ◽  
Author(s):  
Liping Fang ◽  
Ru Liu ◽  
Ling Xu ◽  
Ji Li ◽  
Li-Zhi Huang ◽  
...  

Green rusts (GRs) interlayered with Cl−, SO42−, and CO32− were used to reduce tetrabromobisphenol A (TBBPA), which is the most widely used brominated flame retardant.


2007 ◽  
Vol 408 (3) ◽  
pp. 407-415 ◽  
Author(s):  
Oluseye A. Ogunbayo ◽  
Francesco Michelangeli

TBBPA (tetrabromobisphenol A) is currently the most widely used type of BFR (brominated flame retardant) employed to reduce the combustibility of a large variety of electronic and other manufactured products. Recent studies have indicated that BFRs, including TBBPA, are bio-accumulating within animal and humans. BFRs including TBBPA have also been shown to be cytotoxic and potentially endocrine-disrupting to a variety of cells in culture. Furthermore, TBBPA has specifically been shown to cause disruption of Ca2+ homoeostasis within cells, which may be the underlying cause of its cytotoxicity. In this study, we have demonstrated that TBBPA is a potent non-isoform-specific inhibitor of the SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) (apparent Ki 0.46–2.3 μM), thus we propose that TBBPA inhibition of SERCA contributes in some degree to Ca2+ signalling disruption. TBBPA binds directly to the SERCA without the need to partition into the phospholipid bilayer. From activity results and Ca2+-induced conformational results, it appears that the major effect of TBBPA is to decrease the SERCA affinity for Ca2+ (increasing the Kd from approx. 1 μM to 30 μM in the presence of 10 μM TBBPA). Low concentrations of TBBPA can quench the tryptophan fluorescence of the SERCA and this quenching can be reversed by BHQ [2,5-di-(t-butyl)-1,4-hydroquinone] and 4-n-nonylphenol, but not thapsigargin, indicating that TBBPA and BHQ may be binding to similar regions in the SERCA.


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