scholarly journals Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2099 ◽  
Author(s):  
Danielle M. Felber ◽  
Yuze Wu ◽  
Ningning Zhao

The metal transporters ZIP14 and ZnT10 play key physiological roles in maintaining manganese (Mn) homeostasis. However, in vivo regulation of these two transporters by Mn is not understood. Here, we examined how dietary Mn intake regulates ZIP14 and ZnT10 by feeding mice a low-Mn diet, a control diet, or a high-Mn diet for 6 weeks. Inductively coupled plasma mass spectrometry was used to measure Mn and iron (Fe) levels. ZIP14 and ZnT10 protein levels were measured by western blot analysis. While mice on the high-Mn diet exhibited significantly higher levels of Mn in the blood, liver, and brain, the low-Mn diet group did not display matching reductions, indicating that high Mn intake is more effective in disrupting Mn homeostasis in mice. Additionally, Fe levels were only slightly altered, suggesting independent transport mechanisms for Mn and Fe. In the high-Mn diet group, ZIP14 and ZnT10 were both upregulated in the liver, as well as in the small intestine, indicating a coordinated role for these transporters in Mn excretion. Unexpectedly, this upregulation only occurred in male mice, with the exception of hepatic ZIP14, providing new insight into mechanisms behind widely observed sex differences in Mn homeostasis.

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shene Yi-Shiuan Chiou ◽  
Kai Kysenius ◽  
Yifan Huang ◽  
Mark David Habgood ◽  
Liam M. Koehn ◽  
...  

Abstract Background Little is known about the extent of drug entry into developing brain, when administered to pregnant and lactating women. Lithium is commonly prescribed for bipolar disorder. Here we studied transfer of lithium given to dams, into blood, brain and cerebrospinal fluid (CSF) in embryonic and postnatal animals as well as adults. Methods Lithium chloride in a clinically relevant dose (3.2 mg/kg body weight) was injected intraperitoneally into pregnant (E15–18) and lactating dams (birth-P16/17) or directly into postnatal pups (P0–P16/17). Acute treatment involved a single injection; long-term treatment involved twice daily injections for the duration of the experiment. Following terminal anaesthesia blood plasma, CSF and brains were collected. Lithium levels and brain distribution were measured using Laser Ablation Inductively Coupled Plasma-Mass Spectrometry and total lithium levels were confirmed by Inductively Coupled Plasma-Mass Spectrometry. Results Lithium was detected in blood, CSF and brain of all fetal and postnatal pups following lithium treatment of dams. Its concentration in pups’ blood was consistently below that in maternal blood (30–35%) indicating significant protection by the placenta and breast tissue. However, much of the lithium that reached the fetus entered its brain. Levels of lithium in plasma fluctuated in different treatment groups but its concentration in CSF was stable at all ages, in agreement with known stable levels of endogenous ions in CSF. There was no significant increase of lithium transfer into CSF following application of Na+/K+ ATPase inhibitor (digoxin) in vivo, indicating that lithium transfer across choroid plexus epithelium is not likely to be via the Na+/K+ ATPase mechanism, at least early in development. Comparison with passive permeability markers suggested that in acute experiments lithium permeability was less than expected for diffusion but similar in long-term experiments at P2. Conclusions Information obtained on the distribution of lithium in developing brain provides a basis for studying possible deleterious effects on brain development and behaviour in offspring of mothers undergoing lithium therapy.


Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 964
Author(s):  
Jana Möckel ◽  
Julia Brangsch ◽  
Carolin Reimann ◽  
Jan O. Kaufmann ◽  
Ingolf Sack ◽  
...  

Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis.


2021 ◽  
Vol 12 (3) ◽  
pp. 033-044
Author(s):  
Trupti Patil ◽  
Asmita Wele ◽  
Sangram Patil

Background: Gold bhasma [Swarnabhasma] is a ancient Ayurvedic medicine used for rejuvenation and longevity. This is a preliminary attempt to study the bioavailability of this medicine. Objectives: It was aimed to estimate comparative bioavailability of gold bhasma up to five hours after oral dose with four different anupana. Materials and methods: In this in vivo study, 30 healthy human participants were allocated randomly into five groups having six individuals each. Gold bhasma in 30 mg dose was administered orally with four different anupana viz honey [2.5 gm], black pepper-ghee combination [250 mg and 2.5 gm respectively], lactose [250 mg], glucose [250 mg], and plain to participants in each group. Blood samples were collected at 0, 1, 3 and 5 hours after dose. Gold levels in blood were assessed by inductively coupled plasma mass spectrometry [ICP-MS]. Results: Gold levels in all blood samples were in traces. Average Cmax was 0.002333 microgram of gold per liter and Tmax was at 3 hours for honey anupana, showing maximum Cmax among all groups. Conclusions: Preliminary results indicate that bioavailability of gold from gold bhasma may be less than 0.01 % upto first five hours. Gold bhasma mixed with honey resulted in attainment of maximum Cmax. It is evident that accompanying media [anupana] play an important role in absorption of gold bhasma.


2006 ◽  
Vol 78 (15) ◽  
pp. 5584-5589 ◽  
Author(s):  
Agata Michalska ◽  
Marcin Wojciechowski ◽  
Barbara Wagner ◽  
Ewa Bulska ◽  
Krzysztof Maksymiuk

2007 ◽  
Vol 334-335 ◽  
pp. 1177-1180 ◽  
Author(s):  
Bin Zhang ◽  
Xiao Li Huang ◽  
Lei Ren ◽  
Qi Qing Zhang ◽  
Mei Chee Tan ◽  
...  

We successfully synthesized near infrared (NIR) sensitive Au(shell)-Au2S(core) nanoparticles, where Au2S dielectric core was encapsulated by a thin gold shell. The cytotoxicity in vitro and biodistribution in vivo of Au-Au2S nanoparticles was studied by using NIH3T3 cells and KM mice, respectively. The quantitative analysis of Au in each tissue of mice was done by using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Au-Au2S nanoparticles (< 300 μg/ml) showed good biocompatibility. Au-Au2S nanoparticles were preferentially taken up by the liver and spleen, and ultimately eliminated mostly in the feces.


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