169 results on '"Robert A. Yokel"'
Search Results
2. Aluminum reproductive toxicity: a summary and interpretation of scientific reports
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Robert A. Yokel
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Physiology ,010501 environmental sciences ,Toxicology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Placenta ,medicine ,Animals ,Humans ,Testosterone ,030304 developmental biology ,0105 earth and related environmental sciences ,0303 health sciences ,Fetus ,Reproductive function ,business.industry ,Reproduction ,Malondialdehyde ,Bioavailability ,medicine.anatomical_structure ,chemistry ,Environmental Pollutants ,Animal studies ,Reproductive toxicity ,business ,Aluminum - Abstract
Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and rats was evident after exposure to ≥25-fold the amount of Al consumed in the diet. Generally, the additional daily Al systemic exposure of studies that reported statistically significant results was greater than 100-fold above the typical human daily Al dietary consumption equivalent. Male reproductive endpoints were significantly affected after exposure to lower levels of Al than females. Increased Al intake increased fetus, placenta, and testes Al concentrations, to a greater extent in the placenta than fetus, and, in some cases, more in the testes than placenta. An adverse outcome pathway (AOP) was constructed for males based on the results of the reviewed studies. The proposed AOP includes oxidative stress as the molecular initiating event and increased malondialdehyde, DNA and spermatozoal damage, and decreased blood testosterone and sperm count as subsequent key events. Recommendations for the design of future studies of reproductive outcomes following exposure to Al are provided.
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- 2020
3. Tissue Specific Fate of Nanomaterials by Advanced Analytical Imaging Techniques - A Review
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David A. Bennett, Joseph D. Brain, Jennifer Weuve, Alan Dozier, Uschi M. Graham, Günter Oberdörster, Robert A. Yokel, Ramon M. Molina, and Jayant M. Pinto
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Chemical imaging ,0303 health sciences ,Materials science ,Electron energy loss spectroscopy ,Energy-dispersive X-ray spectroscopy ,Nanoparticle ,Nanotechnology ,General Medicine ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Article ,Nanostructures ,Nanomaterials ,03 medical and health sciences ,Microscopy, Electron, Transmission ,Organ Specificity ,Scanning transmission electron microscopy ,Particle ,030304 developmental biology ,0105 earth and related environmental sciences ,Biomineralization - Abstract
A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy. These tools can be used to analyze particle location, translocation and potential reformation, ion dispersion, and in vivo synthesis of second-generation nanoparticles. Such analyses can provide in depth understanding of tissue–particle interactions and effects that are caused by the environmental “invader” nanoparticles. Analytical imaging can also distinguish phases that form due to the transformation of “invader” nanoparticles in contrast to those that are triggered by a response mechanism, including the commonly observed iron biomineralization in the form of ferritin nanoparticles. The analyses can distinguish ion species, crystal phases, and valence of parent nanoparticles and reformed or in vivo synthesized phases throughout the tissue. This article will briefly review the plethora of methods that have been developed over the last 20 years with an emphasis on the state-of-the-art techniques used to image and analyze nanoparticles in cells and highlight the sample preparation necessary for biological thin section observation in a HRSTEM. Specific applications that provide visual and chemical mapping of the local cellular environments surrounding parent nanoparticles and second-generation phases are demonstrated, which will help to identify novel nanoparticle-produced adverse effects and their associated mechanisms.
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- 2020
4. Contributors
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Jan Aaseth, Peter Aggett, Antero Aitio, Agneta Åkesson, Maria Albin, Jan Alexander, Christian B.I. Andersen, Ole Andersen, Pietro Apostoli, Michael Aschner, Rowa Bakadlag, Lars Barregard, David C. Bellinger, Ingvar A. Bergdahl, Balazs Berlinger, Alfred Bernard, Carolina Bigert, Poul Bjerregaard, Robyn Blain, Lennart K. Blomqvist, Beatrice Bocca, Stephan Bose-O'Reilly, Karin Broberg, Ronald P. Brown, Esben Budtz-Jørgensen, Samuel W. Caito, Tiffany Carle, Chien-Jen Chen, Xiao Chen, Lung-Chi Chen, C.-H. Selene J. Chou, Mitchell D. Cohen, Max Costa, Giuseppe De Palma, Alison Elder, Carl-Gustaf Elinder, Bengt Fadeel, Obaid M. Faroon, Bruce A. Fowler, Hitomi Fujishiro, Silvia Fustinoni, Lars Gerhardsson, Philippe Grandjean, Per Gustavsson, Yolanda Hedberg, Seiichiro Himeno, Xi Huang, Per A. Hultman, Ivo Iavicoli, Taiyi Jin, Robert L. Jones, Hanna L. Karlsson, Larry S. Keith, Yangho Kim, Catherine B. Klein, Michael Kleinman, David Kotelchuck, Yukinori Kusaka, Philip J. Landrigan, Per E. Leffler, Veruscka Leso, Alex Heng Li, Dominique Lison, Shan Liu, Roberto G. Lucchini, Polina Maciejczyk, Koren K. Mann, Nikki Maples-Reynolds, Michael J. Maroney, Airton C. Martins, Mary S. Matsui, Daphne B. Moffett, Lisbeth Birk Møller, M. Moiz Mumtaz, Makiko Nakano, Benoit Nemery, Koji Nogawa, Gunnar F. Nordberg, Monica Nordberg, Angelica Ortiz, Agneta Oskarsson, Elena A. Ostrakhovitch, Cezary M. Pałczyński, Natalia Pawlas, Daniela Pelclova, Maria Pesonen, K. Michael Pollard, Lothar Rink, Flavia Ruggieri, Patricia Ruiz, Harold H. Sandstead, Tiina Santonen, Kazuhiro Sato, Hiroshi Satoh, Deepak Saxena, Greet Schoeters, Bengt Sjögren, Staffan Skerfving, Donald R. Smith, Dexter W. Sullivan, Daigo Sumi, Hong Sun, Hille Suojalehto, Akiyo Tanaka, Milton Tenenbein, George D. Thurston, Francisco A. Tomei Torres, Muhammet S. Toprak, Carolyn A. Tylenda, Julian F. Tyson, Tomohiro Umemura, Margaret H. Whittaker, Jana Wolf, Wenbo Yan, Robert A. Yokel, and Rudolfs K. Zalups
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- 2022
5. Aluminum
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Robert A. Yokel and Bengt Sjögren
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- 2022
6. Simulated biological fluid exposure changes nanoceria’s surface properties but not its biological response
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Matthew L. Hancock, Marsha L. Ensor, Alexandra J. Brooks, Hemendra J. Vekaria, Eric A. Grulke, Patrick G. Sullivan, Benjamin Cherian, and Robert A. Yokel
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Cell Survival ,Surface Properties ,Cellular respiration ,Pharmaceutical Science ,chemistry.chemical_element ,02 engineering and technology ,engineering.material ,medicine.disease_cause ,030226 pharmacology & pharmacy ,Oxygen ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Oxygen Consumption ,0302 clinical medicine ,Coating ,Cell Line, Tumor ,medicine ,Zeta potential ,Humans ,Biological activity ,Resazurin ,Cerium ,General Medicine ,021001 nanoscience & nanotechnology ,Body Fluids ,Mitochondria ,Oxidative Stress ,chemistry ,A549 Cells ,engineering ,Biophysics ,Nanoparticles ,Caco-2 Cells ,0210 nano-technology ,Citric acid ,Oxidation-Reduction ,Oxidative stress ,Biotechnology - Abstract
Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce(3+) and Ce(4+), giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria’s surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria’s surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria’s surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates.
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- 2019
7. Plasma and Serum Proteins Bound to Nanoceria: Insights into Pathways by which Nanoceria may Exert Its Beneficial and Deleterious Effects
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Allan D, Butterfield, Binghui, Wang, Peng, Wu, Sarita S, Hardas, Jason M, Unrine, Eric A, Grulke, Jian, Cai, Jon B, Klein, William M, Pierce, Robert A, Yokel, and Rukhsana, Sultana
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Serum ,Proteomics ,Plasma ,Nanoceria ,Protein corona ,Article - Abstract
Nanoceria (CeO2, cerium oxide nanoparticles) is proposed as a therapeutic for multiple disorders. In blood, nanoceria becomes protein-coated, changing its surface properties to yield a different presentation to cells. There is little information on the interaction of nanoceria with blood proteins. The current study is the first to report the proteomics identification of plasma and serum proteins adsorbed to nanoceria. The results identify a number of plasma and serum proteins interacting with nanoceria, proteins whose normal activities regulate numerous cell functions: antioxidant/detoxification, energy regulation, lipoproteins, signaling, complement, immune function, coagulation, iron homeostasis, proteolysis, inflammation, protein folding, protease inhibition, adhesion, protein/RNA degradation, and hormonal. The principal implications of this study are: 1) The protein corona may positively or negatively affect nanoceria cellular uptake, subsequent organ bioprocessing, and effects; and 2) Nanoceria adsorption may alter protein structure and function, including pro- and inflammatory effects. Consequently, prior to their use as therapeutic agents, better understanding of the effects of nanoceria protein coating is warranted.
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- 2021
8. Laser irradiation as a novel alternative to detach intact particulate matter collected on air filters
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Hedieh Pazokian, Seyed-Mohammadreza Samaee, Robert A. Yokel, and Rahim Molaei
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Air Pollutants ,Environmental Engineering ,Materials science ,Health, Toxicology and Mutagenesis ,Lasers ,Extraction (chemistry) ,Public Health, Environmental and Occupational Health ,Analytical chemistry ,Single step ,General Medicine ,General Chemistry ,Particulates ,Laser ,Pollution ,law.invention ,Filter (aquarium) ,Air Filters ,law ,Environmental Chemistry ,Gravimetric analysis ,Particulate Matter ,Irradiation ,Air filter ,Environmental Monitoring - Abstract
Airborne particulate matter (PM) is collected on specific filters. For subsequent testing, the PM should be detached intact from the filter. Liquid extraction (LE), the standard method to detach PM from air filter surfaces, is challenging and can be tedious. Laser irradiation has been used to characterize PM on filters, but not to detach PM from filters for subsequent testing. A feasibility study was conducted to assess the potential of laser irradiation to detach PM from air filters. Laser-detached PM was deposited on a pre-weighed glass plate. PM detachment and collection were conducted in a single step. PM-coated air filters were subjected to visual inspection, gravimetric assessment of captured PM, and spectroscopic scanning (ATR-FTIR, SEM-EDS, and XRD) before and after laser irradiation. Laser irradiation PM detachment efficiency was up to 78 %. Functional groups, elements, and minerals of PM collected on filter surfaces disappeared or significantly decreased after irradiation, demonstrating detachment, without suffering a change in their nature. No evidence of filter fragments was found in the detached PM. Laser irradiation was i) an easy, ii) rapid, and iii) single step procedure that iv) detached PM, v) didn't detach filter fragments, vi) didn't change PM composition, and vii) is amenable to automation and high throughput. Laser irradiation to detach PM from air filters as an alternative to LE is worthy of further study and development.
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- 2021
9. Cerium dioxide, a Jekyll and Hyde nanomaterial, can increase basal and decrease elevated inflammation and oxidative stress
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Robert A. Yokel, Marsha L. Ensor, Hemendra J. Vekaria, Patrick G. Sullivan, David J. Feola, Arnold Stromberg, Michael T. Tseng, and Douglas A. Harrison
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Inflammation ,Oxidative Stress ,Arginase ,Biomedical Engineering ,Humans ,Pharmaceutical Science ,Molecular Medicine ,Medicine (miscellaneous) ,General Materials Science ,Bioengineering ,Cerium ,Nanostructures - Abstract
It was hypothesized that the catalyst nanoceria can increase inflammation/oxidative stress from the basal and reduce it from the elevated state. Macrophages clear nanoceria. To test the hypothesis, M0 (non-polarized), M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated, regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Inflammatory responses were quantified by IL-1β level, arginase activity, and RT-qPCR and metabolic changes and oxidative stress by the mito and glycolysis stress tests (MST and GST). Morphology was determined by light microscopy, macrophage phenotype marker expression, and a novel three-dimensional immunohistochemical method. Nanoceria blocked IL-1β and arginase effects, increased M0 cell OCR and GST toward the M2 phenotype and altered multiple M1- and M2-like cell endpoints toward the M0 level. M1-like cells had greater volume and less circularity/roundness. M2-like cells had greater volume than M0 macrophages. The results are overall consistent with the hypothesis.
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- 2022
10. Morphometric characteristics and time to hatch as efficacious indicators for potential nanotoxicity assay in zebrafish
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Seyed-Mohammadreza Samaee, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani, and Nafiseh Manteghi
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0301 basic medicine ,Larva ,animal structures ,Hatching ,Health, Toxicology and Mutagenesis ,Embryo ,010501 environmental sciences ,Biology ,biology.organism_classification ,01 natural sciences ,Acute toxicity ,Andrology ,03 medical and health sciences ,030104 developmental biology ,embryonic structures ,Environmental Chemistry ,Survival rate ,Zebrafish ,0105 earth and related environmental sciences - Abstract
Although the effects of nano-sized titania (nTiO2 ) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO2 exposure (i.e., the effects of nTiO2 -induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO2 (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times from 34 to 202 hpe) were recorded. Total hatching (rate at 106 hpe) was significantly and positively correlated to survival rate, but there was no direct association between nTiO2 -induced change in hatching time (hatching rate at 58 and 82 hpe) and survival rate. At 58, 82, and 106 hpe, morphometric characteristics were significantly correlated to hatching rate, suggesting that the nTiO2 -induced change in hatching time can affect larval development. The morphometric characteristics that were associated with change in hatching time were also significantly correlated to survival rate, suggesting an indirect significant influence of the nTiO2 -induced change in hatching time on survivability. These results show a significant influence of nTiO2 -induced change in hatching events on zebrafish embryo-larvae development and survivability. They also show that morphometric maldevelopments can predict later-in-life consequences (survivability) of an embryonic exposure to nTiO2 . This suggests that zebrafish can be sensitive biological predictors of nTiO2 acute toxicity. Environ Toxicol Chem 2018;37:3063-3076. © 2018 SETAC.
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- 2018
11. Correction to Some Statements about Aluminum in Sulaiman
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Robert A. Yokel
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business.industry ,Chemistry ,General Medicine ,Toxicology ,medicine.disease ,computer.software_genre ,Autism spectrum disorder ,medicine ,Humans ,Artificial intelligence ,business ,computer ,Natural language processing ,Aluminum - Published
- 2021
12. Contributors
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Jan Aaseth, Peter Aggett, Antero Aitio, Agneta Åkesson, Maria Albin, Jan Alexander, Christian B.I. Andersen, Ole Andersen, Pietro Apostoli, Michael Aschner, Rowa Bakadlag, Lars Barregard, David C. Bellinger, Ingvar A. Bergdahl, Balazs Berlinger, Alfred Bernard, Carolina Bigert, Poul Bjerregaard, Robyn Blain, Lennart K. Blomqvist, Beatrice Bocca, Stephan Bose-O'Reilly, Karin Broberg, Ronald P. Brown, Esben Budtz-Jørgensen, Samuel W. Caito, Tiffany Carle, Chien-Jen Chen, Xiao Chen, Lung-Chi Chen, C.-H. Selene J. Chou, Mitchell D. Cohen, Max Costa, Giuseppe De Palma, Alison Elder, Carl-Gustaf Elinder, Bengt Fadeel, Obaid M. Faroon, Bruce A. Fowler, Hitomi Fujishiro, Silvia Fustinoni, Lars Gerhardsson, Philippe Grandjean, Per Gustavsson, Yolanda Hedberg, Seiichiro Himeno, Xi Huang, Per A. Hultman, Ivo Iavicoli, Taiyi Jin, Robert L. Jones, Hanna L. Karlsson, Larry S. Keith, Yangho Kim, Catherine B. Klein, Michael Kleinman, David Kotelchuck, Yukinori Kusaka, Philip J. Landrigan, Per E. Leffler, Veruscka Leso, Alex Heng Li, Dominique Lison, Shan Liu, Roberto G. Lucchini, Polina Maciejczyk, Koren K. Mann, Nikki Maples-Reynolds, Michael J. Maroney, Airton C. Martins, Mary S. Matsui, Daphne B. Moffett, Lisbeth Birk Møller, M. Moiz Mumtaz, Makiko Nakano, Benoit Nemery, Koji Nogawa, Gunnar F. Nordberg, Monica Nordberg, Angelica Ortiz, Agneta Oskarsson, Elena A. Ostrakhovitch, Cezary M. Pałczyński, Natalia Pawlas, Daniela Pelclova, Maria Pesonen, K. Michael Pollard, Lothar Rink, Flavia Ruggieri, Patricia Ruiz, Harold H. Sandstead, Tiina Santonen, Kazuhiro Sato, Hiroshi Satoh, Deepak Saxena, Greet Schoeters, Bengt Sjögren, Staffan Skerfving, Donald R. Smith, Dexter W. Sullivan, Daigo Sumi, Hong Sun, Hille Suojalehto, Akiyo Tanaka, Milton Tenenbein, George D. Thurston, Francisco A. Tomei Torres, Muhammet S. Toprak, Carolyn A. Tylenda, Julian F. Tyson, Tomohiro Umemura, Margaret H. Whittaker, Jana Wolf, Wenbo Yan, Robert A. Yokel, and Rudolfs K. Zalups
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- 2021
13. Nanoceria distribution and effects are mouse-strain dependent
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Matthew L. Hancock, Michael T. Tseng, Jason M. Unrine, Arnold J. Stromberg, Uschi M. Graham, D. Allan Butterfield, Alan Dozier, Eric A. Grulke, and Robert A. Yokel
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Cerium oxide ,Surface Properties ,Biomedical Engineering ,Caspase 1 ,Nanoparticle ,02 engineering and technology ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Article ,Phosphates ,Mice ,Immune system ,Species Specificity ,Distribution (pharmacology) ,Animals ,Tissue Distribution ,0105 earth and related environmental sciences ,Mice, Inbred BALB C ,Mouse strain ,biology ,Chemistry ,Cerium ,021001 nanoscience & nanotechnology ,Ferritin ,Mice, Inbred C57BL ,Microscopy, Electron ,Oxidative Stress ,Liver ,biology.protein ,Biophysics ,Nanoparticles ,Female ,0210 nano-technology ,Spleen - Abstract
Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. OBJECTIVE: Assess nanoceria (cerium oxide, CeO2 nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. METHODS: C57BL/6 and BALB/c female mice were i.p. injected with 10mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. RESULTS: Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. Light microscopy revealed greater liver vacuolation in C57BL/6 mice and a nanoceria-induced decrease in BALB/c but not C57BL/6 mice vacuolation. Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. Electron microscopy showed intracellular nanoceria particles bioprocessed to form crystalline cerium phosphate nanoneedles. Ferritin accumulation was greatly increased proximal to the nanoceria, forming core-shell-like structures in C57BL/6 but even distribution in BALB/c mice. CONCLUSIONS: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. Nanoceria uptake, initiation of bioprocessing, and crystalline cerium phosphate nanoneedle formation were rapid. Ferritin greatly increased with a macrophage phenotype-dependent distribution. Further study will be needed to understand the mechanisms underlying the observed differences.
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- 2020
14. Nanoparticle brain delivery: a guide to verification methods
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Robert A. Yokel
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Microdialysis ,Pathology ,medicine.medical_specialty ,business.industry ,Biomedical Engineering ,Medicine (miscellaneous) ,Blood-cerebrospinal fluid barrier ,Brain ,Bioengineering ,Development ,Blood–brain barrier ,Peripheral ,Cerebrospinal fluid ,medicine.anatomical_structure ,Blood-Brain Barrier ,Parenchyma ,Extracellular ,medicine ,Animals ,Humans ,Nanoparticles ,General Materials Science ,Convection-Enhanced Delivery ,business - Abstract
Many reports conclude nanoparticle (NP) brain entry based on bulk brain analysis. Bulk brain includes blood, cerebrospinal fluid and blood vessels within the brain contributing to the blood–brain and blood–cerebrospinal fluid barriers. Considering the brain as neurons, glia and their extracellular space (brain parenchyma), most studies did not show brain parenchymal NP entry. Blood–brain and blood–cerebrospinal fluid barriers anatomy and function are reviewed. Methods demonstrating brain parenchymal NP entry are presented. Results demonstrating bulk brain versus brain parenchymal entry are classified. Studies are reviewed, critiqued and classified to illustrate results demonstrating bulk brain versus parenchymal entry. Brain, blood and peripheral organ NP timecourses are compared and related to brain parenchymal entry evidence suggesting brain NP timecourse informs about brain parenchymal entry.
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- 2020
15. Physiologically based pharmacokinetic modeling of nanoceria systemic distribution in rats suggests dose- and route-dependent biokinetics
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Robert A. Yokel, Gunnar Johanson, Tshepo Paulsen Moto, Ulrika Carlander, and Anteneh Assefa Desalegn
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Physiologically based pharmacokinetic modelling ,Biodistribution ,Pharmacokinetic modeling ,Biophysics ,Pharmaceutical Science ,Administration, Oral ,Bioengineering ,02 engineering and technology ,Absorption (skin) ,010402 general chemistry ,01 natural sciences ,Models, Biological ,Biomaterials ,Rats, Sprague-Dawley ,oral ,Pharmacokinetics ,International Journal of Nanomedicine ,Drug Discovery ,Administration, Inhalation ,Distribution (pharmacology) ,Animals ,Humans ,Tissue Distribution ,biodistribution ,Original Research ,inhalation ,Inhalation ,Chemistry ,Organic Chemistry ,General Medicine ,Cerium ,021001 nanoscience & nanotechnology ,cerium dioxide ,0104 chemical sciences ,Target dose ,instillation ,Liver ,intravenous ,Calibration ,Nanoparticles ,0210 nano-technology ,Spleen ,Biomedical engineering - Abstract
Ulrika Carlander,1 Tshepo Paulsen Moto,2 Anteneh Assefa Desalegn,1 Robert A Yokel,3 Gunnar Johanson1 1Unit of Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden; 2Faculty ofHealth Sciences, School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa; 3Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA Background: Cerium dioxide nanoparticles (nanoceria) are increasingly being used in a variety of products as catalysts, coatings, and polishing agents. Furthermore, their antioxidant properties make nanoceria potential candidates for biomedical applications. To predict and avoid toxicity, information about their biokinetics is essential. A useful tool to explore such associations between exposure and internal target dose is physiologically based pharmacokinetic (PBPK) modeling. The aim of this study was to test the appropriateness of our previously published PBPK model developed for intravenous (IV) administration when applied to various sizes of nanoceria and to exposure routes relevant for humans. Methods: Experimental biokinetic data on nanoceria (obtained from various exposure routes, sizes, coatings, doses, and tissues sampled) in rats were collected from the literature and also obtained from the researchers. The PBPK model was first calibrated and validated against IV data for 30 nm citrate coated ceria and then recalibrated for 5 nm ceria. Finally, the model was modified and tested against inhalation, intratracheal (IT) instillation, and oral nanoceria data.Results: The PBPK model adequately described nanoceria time courses in various tissues for 5 nm ceria given IV. The time courses of 30 nm ceria were reasonably well predicted for liver and spleen, whereas the biokinetics in other tissues were not well captured. For the inhalation, IT instillation, and oral exposure routes, re-optimization was difficult due to low absorption and, hence, low and variable nanoceria tissue levels. Moreover, the nanoceria properties and exposure conditions varied widely among the inhalation, IT instillation, and oral studies, making it difficult to assess the importance of different factors. Conclusion: Overall, our modeling efforts suggest that nanoceria biokinetics depend largely on the exposure route and dose. Keywords: biodistribution, cerium dioxide, inhalation, instillation, intravenous, oral
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- 2018
16. Analytical High-resolution Electron Microscopy Reveals Organ-specific Nanoceria Bioprocessing
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Joseph E. Fernback, Alan Dozier, Uschi M. Graham, Eileen Birch, Krishnamurthy Mahalingam, Michael T. Tseng, Lawrence F. Drummy, and Robert A. Yokel
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Male ,0301 basic medicine ,Nanoparticle ,02 engineering and technology ,Toxicology ,Article ,Pathology and Forensic Medicine ,Nanomaterials ,Rats, Sprague-Dawley ,03 medical and health sciences ,In vivo ,Scanning transmission electron microscopy ,Microscopy ,Animals ,Molecular Biology ,Chemistry ,Electron energy loss spectroscopy ,Cerium ,Cell Biology ,021001 nanoscience & nanotechnology ,Dark field microscopy ,Rats ,Microscopy, Electron ,030104 developmental biology ,Liver ,Transmission electron microscopy ,Biophysics ,0210 nano-technology ,Spleen - Abstract
This is the first utilization of advanced analytical electron microscopy methods, including high-resolution transmission electron microscopy, high-angle annular dark field scanning transmission electron microscopy, electron energy loss spectroscopy, and energy-dispersive X-ray spectroscopy mapping to characterize the organ-specific bioprocessing of a relatively inert nanomaterial (nanoceria). Liver and spleen samples from rats given a single intravenous infusion of nanoceria were obtained after prolonged (90 days) in vivo exposure. These advanced analytical electron microscopy methods were applied to elucidate the organ-specific cellular and subcellular fate of nanoceria after its uptake. Nanoceria is bioprocessed differently in the spleen than in the liver.
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- 2017
17. Biokinetics of nanomaterials: The role of biopersistence
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Andreas Schäffer, Gunnar Johanson, Peter Laux, Josephine Brunner, Joseph D. Brain, Thomas Gebel, Cristina Cerrillo, Heiko Kock, Andy M. Booth, Harald Jungnickel, Andreas Luch, Jutta Tentschert, Ahmed Tlili, Christian Riebeling, Robert A. Yokel, Adriënne J.A.M. Sips, Otto Creutzenberg, Irina Estrela-Lopis, and Publica
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0301 basic medicine ,Extrapulmonary organs ,Chemistry ,Materials Science (miscellaneous) ,extrapulmonary organ ,Public Health, Environmental and Occupational Health ,Biokinetics ,biokinetic ,Nanotechnology ,02 engineering and technology ,Granular biopersistent particle without known significant specific toxicity (GBP) ,021001 nanoscience & nanotechnology ,Article ,inhalation exposure ,03 medical and health sciences ,030104 developmental biology ,Inhalation ,Dosimetry ,0210 nano-technology ,Safety, Risk, Reliability and Quality ,Safety Research ,Exposure assessment - Abstract
NanoImpact : an international journal of nanosafety research 6, 69-80 (2017). doi:10.1016/j.impact.2017.03.003, Published by Elsevier, Amsterdam
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- 2017
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18. Surface-controlled dissolution rates: a case study of nanoceria in carboxylic acid solutions
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Matthew L. Hancock, Jason M. Unrine, Robert A. Yokel, Matthew J. Beck, Eric A. Grulke, and Uschi M. Graham
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chemistry.chemical_classification ,Materials Science (miscellaneous) ,Carboxylic acid ,Nanoparticle ,chemistry.chemical_element ,02 engineering and technology ,010501 environmental sciences ,021001 nanoscience & nanotechnology ,01 natural sciences ,Article ,Cerium ,Membrane ,chemistry ,Chemical engineering ,Particle size ,0210 nano-technology ,Dispersion (chemistry) ,Dissolution ,Inductively coupled plasma mass spectrometry ,0105 earth and related environmental sciences ,General Environmental Science - Abstract
Nanoparticle dissolution in local milieu can affect their ecotoxicity and therapeutic applications. For example, carboxylic acid release from plant roots can solubilize nanoceria in the rhizosphere, affecting cerium uptake in plants. Nanoparticle dispersions were dialyzed against ten carboxylic acid solutions for up to 30 weeks; the membrane passed cerium-ligand complexes but not nanoceria. Dispersion and solution samples were analyzed for cerium by inductively coupled plasma mass spectrometry (ICP-MS). Particle size and shape distributions were measured by transmission electron microscopy (TEM). Nanoceria dissolved in all carboxylic acid solutions, leading to cascades of progressively smaller nanoparticles and producing soluble products. The dissolution rate was proportional to nanoparticle surface area. Values of the apparent dissolution rate coefficients varied with the ligand. Both nanoceria size and shape distributions were altered by the dissolution process. Density functional theory (DFT) estimates for some possible Ce(IV) products showed that their dissolution was thermodynamically favored. However, dissolution rate coefficients did not generally correlate with energy of formation values. The surface-controlled dissolution model provides a quantitative measure for nanoparticle dissolution rates: further studies of dissolution cascades should lead to improved understanding of mechanisms and processes at nanoparticle surfaces.
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- 2019
19. Carboxylic Acids Accelerate Acidic Environment-Mediated Nanoceria Dissolution
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Alan Dozier, Eric A. Grulke, Uschi M. Graham, Robert A. Yokel, Matthew L. Hancock, and Jason M. Unrine
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chemistry.chemical_classification ,Aqueous solution ,Surface Properties ,Carboxylic acid ,Biomedical Engineering ,Carboxylic Acids ,02 engineering and technology ,Cerium ,010501 environmental sciences ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Toxicology ,Ligands ,01 natural sciences ,Article ,chemistry ,Microscopy, Electron, Transmission ,Solubility ,Nanoparticles ,Particle Size ,0210 nano-technology ,Dissolution ,Oxidation-Reduction ,0105 earth and related environmental sciences ,Nuclear chemistry - Abstract
Ligands that accelerate nanoceria dissolution may greatly affect its fate and effects. This project assessed carboxylic acid contribution to nanoceria dissolution in aqueous, acidic environments. Nanoceria has commercial and potential therapeutic and energy storage applications. It biotransforms in vivo. Citric acid stabilizes nanoceria during synthesis and in aqueous dispersions. In this study, citrate-stabilized nanoceria dispersions (~ four nm average primary particle size) were loaded into dialysis cassettes whose membranes passed cerium salts but not nanoceria particles. The cassettes were immersed in iso-osmotic baths containing carboxylic acids at pH 4.5 and 37 °C, or other select agents. Cerium atom material balances were conducted for the cassette and bath by sampling of each chamber and cerium quantitation by ICP-MS. Samples were collected from the cassette for high-resolution transmission electron microscopy observation of nanoceria size. In carboxylic acid solutions, nanoceria dissolution increased bath cerium concentration to > 96% of the cerium introduced as nanoceria into the cassette and decreased nanoceria primary particle size in the cassette. In solutions of citric, malic, and lactic acids and the ammonium ion ~ 15 nm ceria agglomerates persisted. In solutions of other carboxylic acids, some select nanoceria agglomerates grew to ~ one micron. In carboxylic acid solutions dissolution half-lives were 800 to 4000 h; in water and horseradish peroxidase they were ≥ 55,000 h. Extending these findings to in vivo and environmental systems, one expects acidic environments containing carboxylic acids to degrade nanoceria by dissolution; two examples would be phagolysosomes and in the plant rhizosphere.
- Published
- 2019
20. Methods to Quantify Nanomaterial Association with, and Distribution Across, the Blood-Brain Barrier In Vivo
- Author
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Robert A, Yokel
- Subjects
Blood-Brain Barrier ,Animals ,Endothelial Cells ,Capillaries ,Nanostructures ,Rats - Abstract
The role and functional anatomy of the blood-brain barrier (BBB) is summarized to enable the investigator to appropriately address evaluation of nanomaterial interaction with, and distribution across, it into brain tissue (parenchyma). Transport mechanisms across the BBB are presented, in relation to nanomaterial physicochemical properties. Measures and test substances to assess BBB integrity/disruption/permeation are introduced, along with how they are used to interpret the results obtained with the presented methods. Experimental pitfalls and misinterpretation of results of studies of brain nanomaterial uptake are briefly summarized, that can be avoided with the methods presented in this chapter. Two methods are presented. The in situ brain perfusion technique is used to determine rate and extent of nanomaterial distribution into the brain. The capillary depletion method separates brain parenchymal tissue from the endothelial cells that contribute to the BBB. It is used to verify nanomaterial brain tissue entry. These methods are best used together, the latter refining the results obtained with the former. Details of the materials and equipment needed to conduct these methods, and description of the procedures and data interpretation, are provided.
- Published
- 2018
21. Methods to Quantify Nanomaterial Association with, and Distribution Across, the Blood–Brain Barrier In Vivo
- Author
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Robert A. Yokel
- Subjects
Chemistry ,Data interpretation ,02 engineering and technology ,Brain tissue ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Blood–brain barrier ,01 natural sciences ,0104 chemical sciences ,medicine.anatomical_structure ,In vivo ,Functional anatomy ,medicine ,Distribution (pharmacology) ,0210 nano-technology ,Biomedical engineering - Abstract
The role and functional anatomy of the blood-brain barrier (BBB) is summarized to enable the investigator to appropriately address evaluation of nanomaterial interaction with, and distribution across, it into brain tissue (parenchyma). Transport mechanisms across the BBB are presented, in relation to nanomaterial physicochemical properties. Measures and test substances to assess BBB integrity/disruption/permeation are introduced, along with how they are used to interpret the results obtained with the presented methods. Experimental pitfalls and misinterpretation of results of studies of brain nanomaterial uptake are briefly summarized, that can be avoided with the methods presented in this chapter. Two methods are presented. The in situ brain perfusion technique is used to determine rate and extent of nanomaterial distribution into the brain. The capillary depletion method separates brain parenchymal tissue from the endothelial cells that contribute to the BBB. It is used to verify nanomaterial brain tissue entry. These methods are best used together, the latter refining the results obtained with the former. Details of the materials and equipment needed to conduct these methods, and description of the procedures and data interpretation, are provided.
- Published
- 2018
22. The characterization of purified citrate-coated cerium oxide nanoparticles prepared via hydrothermal synthesis
- Author
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Matthew L. Hancock, Eric J. Munson, Robert A. Yokel, Julie L. Calahan, Matthew J. Beck, Travis W. Jarrells, George A. Olaniyan, and Eric A. Grulke
- Subjects
Cerium oxide ,Chemistry ,General Physics and Astronomy ,Nanoparticle ,Infrared spectroscopy ,chemistry.chemical_element ,02 engineering and technology ,Surfaces and Interfaces ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,Surfaces, Coatings and Films ,chemistry.chemical_compound ,Cerium ,Adsorption ,Dynamic light scattering ,Zeta potential ,0210 nano-technology ,Citric acid ,Nuclear chemistry - Abstract
Hypothesis Cerium oxide nanoparticles were synthesized using a hydrothermal approach with citric acid as a stabilizing agent. Citric acid adsorption onto the nanoceria particle surface can cease particle formation and create a stable dispersion for an extended shelf life. The product was dialyzed immediately following the synthesis to remove unreacted cerium that could contribute to biological effects. Nanoparticle characterization results are expected to help identify the surface citrate bonding structure. Experiments Many characterization techniques were utilized to determine size, morphology, surface properties, and citrate complexation on the nanoceria particle surface. These included transmission electron microscopy, electron energy loss spectroscopy, dynamic light scattering, x-ray diffraction, thermogravimetric analysis, Fourier-transform infrared spectroscopy, Raman spectroscopy, UV–Vis absorption spectroscopy, zeta potential, and 13C solid-state nuclear magnetic resonance spectroscopy. Findings Primary particles were hexagonal, determined to be 4.2 nm in diameter. The hydrodynamic diameter of the dialyzed product was 10.8 nm. Each agglomerate was estimated to contain an average of 5.7 particles. The citrate coating contained 2.8 citrate molecules/nm2, corresponding to an approximate citrate monolayer. Citrate complexation with the nanoceria surface includes the central carboxyl geminal to the hydroxyl and perhaps one of its terminal carboxyl groups.
- Published
- 2021
23. Challenges in characterizing the environmental fate and effects of carbon nanotubes and inorganic nanomaterials in aquatic systems
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Peter Laux, Gunnar Johanson, Harald Jungnickel, Joseph D. Brain, Christian Riebeling, Ahmed Tlili, Jutta Tentschert, Thomas Gebel, Otto Creutzenberg, Andreas Luch, Robert A. Yokel, Andy M. Booth, Adriënne J.A.M. Sips, Irina Estrela-Lopis, Josephine Brunner, Cristina Cerrillo, Heiko Kock, Andreas Schäffer, and Publica
- Subjects
Materials science ,Materials Science (miscellaneous) ,Aquatic ecosystem ,333.7 ,Nanotechnology ,02 engineering and technology ,Carbon nanotube ,010501 environmental sciences ,021001 nanoscience & nanotechnology ,01 natural sciences ,Aquatic toxicology ,Nanomaterials ,law.invention ,Aquatic organisms ,law ,ddc:333.7 ,Potential source ,Sample preparation ,0210 nano-technology ,0105 earth and related environmental sciences ,General Environmental Science ,Environmental risk assessment - Abstract
Environmental science / Nano 5(1), 48-63 (2018). doi:10.1039/C7EN00594F, Published by Cambridge
- Published
- 2018
24. Alternating Magnetic Field-Induced Hyperthermia Increases Iron Oxide Nanoparticle Cell Association/Uptake and Flux in Blood–Brain Barrier Models
- Author
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Younsoo Bae, Robert A. Yokel, Mo Dan, and Thomas Pittman
- Subjects
Hyperthermia ,Central nervous system ,Cell ,Iron oxide ,Pharmaceutical Science ,Nanoparticle ,Vascular permeability ,Blood–brain barrier ,Ferric Compounds ,Citric Acid ,Article ,Cell Line ,Capillary Permeability ,Mice ,chemistry.chemical_compound ,Dogs ,Nuclear magnetic resonance ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Magnetite Nanoparticles ,Pharmacology ,fungi ,Organic Chemistry ,Equipment Design ,Hyperthermia, Induced ,medicine.disease ,Magnetic Fields ,medicine.anatomical_structure ,chemistry ,Blood-Brain Barrier ,Molecular Medicine ,Flux (metabolism) ,Biotechnology - Abstract
Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux.Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell(®) models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure.AMF-induced hyperthermia for 0.5 h did not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell association/uptake. It also enhanced the flux of CNA-IONPs across the two in vitro BBB models compared to conventional hyperthermia and normothermia, in the absence of cell death. Citrate-IONP flux was not observed under these conditions. AMF-induced hyperthermia also significantly enhanced paracellular pathway flux. The mechanism appears to involve more than the increased temperature surrounding the CNA-IONPs.Hyperthermia induced by AMF activation of CNA-IONPs has potential to increase the BBB permeability of therapeutics for the diagnosis and therapy of various brain diseases.
- Published
- 2014
25. Toxic and Essential Trace Element Content of Commonly Administered Pediatric Oral Medications
- Author
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Sarah E. Seger, Robert A. Yokel, and Jason M. Unrine
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Reference dose ,medicine.medical_specialty ,Minimal risk ,business.industry ,030232 urology & nephrology ,Clinical Investigations ,Guideline ,030204 cardiovascular system & hematology ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,Dietary Reference Intake ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Pharmacology (medical) ,Daily exposure ,business ,Adverse effect ,Maximum Allowable Concentration - Abstract
OBJECTIVES The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications. METHODS Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication's maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral reference dose, permissible or permitted daily exposure, provisional tolerable weekly intake, and tolerable upper intake concentrations. Exposure guidelines utilized for desired effect were adequate intake and recommended dietary allowance. RESULTS Intake of the maximum recommended daily dose by 6-month-olds for 1 week would not deliver more than the exposure guideline of any of the elements, with the exceptions of chromium in several medications and zinc in the pediatric electrolyte solution, if it was consumed for 1 week. CONCLUSIONS Consumed alone, these frequently administered pediatric oral medications would not deliver amounts of toxic elements that exceed established exposure guidelines for adverse effects, nor would most significantly contribute to adequate intake of essential elements.
- Published
- 2017
26. From Dose to Response: In Vivo Nanoparticle Processing and Potential Toxicity
- Author
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Alison Elder, Alan Dozier, Lisa A. DeLouise, Gary Jacobs, Robert A. Yokel, Günter Oberdörster, M. Eileen Birch, Burtron H. Davis, Michael T. Tseng, and Uschi M. Graham
- Subjects
0301 basic medicine ,Chemistry ,Nanoparticle ,Nanotechnology ,Environmental Exposure ,02 engineering and technology ,Environment ,021001 nanoscience & nanotechnology ,Article ,Nanostructures ,Nanomaterials ,03 medical and health sciences ,Human health ,030104 developmental biology ,In vivo ,Humans ,Nanoparticles ,Manufactured nanoparticles ,0210 nano-technology ,Potential toxicity - Abstract
Adverse human health impacts due to occupational and environmental exposures to manufactured nanoparticles are of concern and pose a potential threat to the continued industrial use and integration of nanomaterials into commercial products. This chapter addresses the inter-relationship between dose and response and will elucidate on how the dynamic chemical and physical transformation and breakdown of the nanoparticles at the cellular and subcellular levels can lead to the in vivo formation of new reaction products. The dose-response relationship is complicated by the continuous physicochemical transformations in the nanoparticles induced by the dynamics of the biological system, where dose, bio-processing, and response are related in a non-linear manner. Nanoscale alterations are monitored using high-resolution imaging combined with in situ elemental analysis and emphasis is placed on the importance of the precision of characterization. The result is an in-depth understanding of the starting particles, the particle transformation in a biological environment, and the physiological response.
- Published
- 2017
27. Neurological System
- Author
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Myrtill Simkó, Mats-Olof Mattsson, and Robert A. Yokel
- Subjects
Nervous system ,Point of entry ,medicine.anatomical_structure ,business.industry ,Engineered nanomaterials ,Medicine ,In real life ,business ,Health outcomes ,Neuroscience ,Exposure data ,Neuroinflammation - Abstract
This chapter provides an overview of how engineered nanomaterials can translocate from the point of entry, especially the respiratory tract, to the circulation and possibly pass through the blood–brain barrier (BBB) and have subsequent effects on the brain. Many in vivo and in vitro studies employing metal, metal oxide, nanoscale carbon, or quantum dot nanomaterials (often at doses/concentrations far above those expected in real life) have been performed and show various effects. Thus, no firm conclusions regarding specific adverse health outcomes due to nanomaterial exposure can be drawn at this point. Other types of investigations, for example, epidemiological studies with relevance for nervous system disorders are few and inconclusive. However, there are indications that air pollution, possibly including nanosized particles, can contribute to neuroinflammation and neurodegenerative diseases. Risk assessment regarding the effects of nanomaterials on the nervous system is presently difficult to perform due to lack of specific exposure data and knowledge about the effects of low-dose and long-term exposures.
- Published
- 2017
28. Contributors
- Author
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Harri Alenius, Don Beezhold, Enrico Bergamaschi, Diana Boraschi, Hans Bouwmeester, Luisa Campagnolo, Chunying Chen, Wim H. de Jong, Shareen H. Doak, Dominic Docter, Ken Donaldson, Rodger Duffin, Albert Duschl, Maria Dusinska, Vidana Epa, Bengt Fadeel, Francesca Larese Filon, Irina Guseva Canu, Maureen R. Gwinn, Akihiro Hirose, Karin S. Hougaard, Mark A. Jepson, Jun Kanno, Shirley K. Knauer, Robert Landsiedel, Tu C. Le, Ying Liu, Xuefei Lu, Andrea Magrini, Mats-Olof Mattsson, Agnieszka Mech, Nicholas L. Mills, Nancy A. Monteiro-Riviere, Antonio Pietroiusti, Craig A. Poland, Adriele Prina-Mello, Jennifer B. Raftis, Kirsten Rasmussen, Hubert Rauscher, Elise Rundén-Pran, Ursula G. Sauer, Kai Savolainen, Jürgen Schnekenburger, Galina V. Shurin, Michael R. Shurin, Anna A. Shvedova, Myrtill Simkó, Birgit Sokull-Klüttgen, Roland H. Stauber, Lang Tran, Dana Westmeier, Dave Winkler, Robert A. Yokel, Il Je Yu, Tao Zhu, and Yong Zhu
- Published
- 2017
29. Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts
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Nataliya A. Karyakina, Calvin C. Willhite, Nagarajkumar Yenugadhati, Daniel Krewski, Ian Arnold, Franco Momoli, Robert A. Yokel, and Thomas Wisniewski
- Subjects
Central Nervous System ,Materials science ,Carcinogenesis ,Respiratory System ,chemistry.chemical_element ,Aluminum Hydroxide ,Endocrine System ,Guidelines as Topic ,Kidney ,Toxicology ,Cardiovascular System ,Risk Assessment ,Article ,Metal ,chemistry.chemical_compound ,Vaccine adjuvant ,Risk Factors ,Aluminium ,Occupational Exposure ,Aluminum Oxide ,Animals ,Humans ,Aluminum oxide ,Randomized Controlled Trials as Topic ,Dose-Response Relationship, Drug ,Metallurgy ,Europe ,Gastrointestinal Tract ,Disease Models, Animal ,Liver ,chemistry ,visual_art ,visual_art.visual_art_medium ,Nanoparticles ,Hydroxide ,Occupational exposure ,Aluminum - Abstract
Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007) . Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of "total Al"assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al(+3) to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)(+2) and Al(H2O)6 (+3)] that after complexation with O2(•-), generate Al superoxides [Al(O2(•))](H2O5)](+2). Semireduced AlO2(•) radicals deplete mitochondrial Fe and promote generation of H2O2, O2 (•-) and OH(•). Thus, it is the Al(+3)-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer's disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.
- Published
- 2014
30. Applying accelerator mass spectrometry for low-level detection of complex engineered nanoparticles in biological media
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Binghui Wang, George S. Jackson, Eric A. Grulke, and Robert A. Yokel
- Subjects
Biodistribution ,Clinical Biochemistry ,Metal Nanoparticles ,Pharmaceutical Science ,macromolecular substances ,Mass spectrometry ,Bone and Bones ,Citric Acid ,Mass Spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,In vivo ,Drug Discovery ,Animals ,Particle Size ,Spectroscopy ,Radioisotopes ,Isotope ,Chemistry ,Radiochemistry ,Brain ,Engineered nanoparticles ,Rats ,Liver ,Environmental chemistry ,Particle size ,Citric acid ,Accelerator mass spectrometry - Abstract
Complex engineered nanoparticles (CENPs), which have different core and surface components, are being developed for medicinal, pharmaceutical and industrial applications. One of the key challenges for environmental health and safety assessments of CENPs is to identify and quantity their transformations in biological environments. This study reports the effects of in vivo exposure of citrate-coated nanoalumina with different rare isotope labels on each component. This CENP was dosed to the rat and accelerator mass spectrometry (AMS) was used to quantify 26 Al, 14 C, and their ratio in the dosing material and tissue samples. For CENPs detected in the liver, the rare isotope ratio, 14 C/ 26 Al, was 87% of the dosing material's ratio. The citrate coating on the nanoalumina in the liver was stable or, if it degraded, its metabolites were incorporated with nearby tissues. However, in brain and bone where little alumina was detected, the rare isotope ratio greatly exceeded that of the dosing material. Therefore, in the animal, citrate dissociated from CENPs and redistributed to brain and bone. Tracking both the core and surface components by AMS presents a new approach for characterizing transformations of CENPs components in biological milieu or environments.
- Published
- 2014
31. Nanoceria biodistribution and retention in the rat after its intravenous administration are not greatly influenced by dosing schedule, dose, or particle shape
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Robert A. Yokel, Peng Wu, Jason M. Unrine, Binghui Wang, and Eric A. Grulke
- Subjects
Biodistribution ,Materials science ,Materials Science (miscellaneous) ,Spleen ,Mononuclear phagocyte system ,Pharmacology ,medicine.anatomical_structure ,Toxicity ,Immunology ,medicine ,Distribution (pharmacology) ,Nanorod ,Dosing ,Bone marrow ,General Environmental Science - Abstract
A 30 nm ceria was previously shown to be primarily cleared from systemic circulation into mononuclear phagocyte system organs after its intravenous (IV) administration, where it persisted for 90 days. The aims of these studies were to determine if the biodistribution, persistence, and toxicity of nanocerias are affected by dosing schedule, dose, or particle shape. Given the many demonstrated and ongoing uses of nanocerias; the multitude of applications under investigation; and the many sizes, shapes, and surface functionalizations of ceria; a better understanding of its fate is necessary to advance its safe use. Five and 30 nm cubic/polyhedral ceria and a ceria nanorod (9.9 × 264 nm average diameter and length) were IV infused into rats once. The 5 nm ceria dose was also infused daily for 5 consecutive days. The rats were terminated 1 h to 90 days later. Cerium was determined in multiple organs and blood. Compared to vehicle-infused controls, elevated cerium was seen in all sites. Liver, spleen, and bone marrow (mononuclear phagocyte system components), contained the largest percentage of the dose. When normalized to dose, and compared to results of prior work with these nanocerias, the distribution and retention of repeated and lower doses of 5 and 30 nm ceria and ceria nanorods were not greatly different from much higher doses of the 5 and 30 nm ceria. Higher doses resulted in a greater percentage of uptake by the spleen and bone marrow and a greater percentage of the ceria nanorod dose in the bone marrow 30 days after its administration than the other nanocerias. Overall these results suggest the biodistribution and retention of cerium after IV administration of different sizes, doses, dosing schedules, and nanoceria shapes are more similar than different.
- Published
- 2014
32. Imatinib mesylate effects on zebrafish reproductive success: Gonadal development, gamete quality, fertility, embryo-larvae viability and development, and related genes
- Author
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Robert A. Yokel, Nader Ahmadi, Aliasghar Tehrani, and Seyed-Mohammadreza Samaee
- Subjects
Male ,0301 basic medicine ,Embryo, Nonmammalian ,media_common.quotation_subject ,Embryonic Development ,Gene Expression ,Fertility ,Toxicology ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Gonads ,Zebrafish ,media_common ,Pharmacology ,biology ,Reproductive success ,Reproduction ,Embryo ,biology.organism_classification ,Fecundity ,Spermatozoa ,030104 developmental biology ,Imatinib mesylate ,Larva ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Sperm Motility ,Female ,Folliculogenesis - Abstract
Imatinib (IM) is a tyrosine kinase (TK) inhibitor (TKI) used to treat chronic myeloid leukemia. Clinical case reports and a few laboratory mammal studies provide inconclusive evidence about its deleterious effects on reproduction. The aim of the current study was to evaluate the potential of zebrafish to characterize IM-induced effects on reproduction and clarify IM effects on reproductive success. To this end, we exposed adult zebrafish to four concentrations of IM for 30 days followed by a 30-day depuration period. IM exposure caused a concentration-dependent, irreversible, suppression of folliculogenesis, reversible decrease in sperm density and motility, decreased fecundity and fertility, but no significant change in atretic follicle abundance. We also observed IM-induced premature hatching, but no significant change in embryo-larvae survivability. However, we found significant IM-induced morphometric malformations. IM decreased expression of vegfaa and igf2a (two reproductive-, angiogenic-, and growth-related genes) in testes and ovaries. The results demonstrate IM can induce significant changes in critical reproductive endpoints and zebrafish as a suitable model organism to show effects of IM on reproduction. The findings suggest that TKI effects on reproductive success should be considered.
- Published
- 2019
33. Assessing nanoparticle risk poses prodigious challenges
- Author
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Robert C. MacPhail, Eric A. Grulke, and Robert A. Yokel
- Subjects
Government ,Engineering ,business.industry ,Disclaimer ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,computer.software_genre ,Public domain ,CLARION ,Work (electrical) ,Risk analysis (engineering) ,Hazardous waste ,Agency (sociology) ,Data mining ,business ,Risk assessment ,computer - Abstract
Risk assessment is used both formally and informally to estimate the likelihood of an adverse event occurring, for example, as a consequence of exposure to a hazardous chemical, drug, or other agent. Formal risk assessments in government regulatory agencies have a long history of practice. The precision with which risk can be estimated is inevitably constrained, however, by uncertainties arising from the lack of pertinent data. Developing accurate risk assessments for nanoparticles and nanoparticle-containing products may present further challenges because of the unique properties of the particles, uncertainties about their composition and the populations exposed to them, and how these may change throughout the particle's life cycle. This review introduces the evolving practice of risk assessment followed by some of the uncertainties that need to be addressed to improve our understanding of nanoparticle risks. Given the clarion call for life-cycle assessments of nanoparticles, an unprecedented degree of national and international coordination between scientific organizations, regulatory agencies, and stakeholders will be required to achieve this goal. WIREs Nanomed Nanobiotechnol 2013, 5:374–387. doi: 10.1002/wnan.1216 For further resources related to this article, please visit the WIREs website. This article is a U.S. Government work, and as such, is in the public domain in the United States of America. Disclaimer: This manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. The approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
- Published
- 2013
34. Metal-based nanoparticle interactions with the nervous system: the challenge of brain entry and the risk of retention in the organism
- Author
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Robert C. MacPhail, Robert A. Yokel, and Eric A. Grulke
- Subjects
Nervous system ,Biomedical Engineering ,Medicine (miscellaneous) ,Nanoparticle ,Bioengineering ,Nanotechnology ,Biology ,Blood–brain barrier ,In vitro ,medicine.anatomical_structure ,Dorsal root ganglion ,In vivo ,Parenchyma ,medicine ,Biophysics ,Organism - Abstract
This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical-chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in vivo methods, and very few human studies. The routes of uptake into the nervous system and mechanisms of nanoparticle uptake by cells are presented with examples. Brain nanoparticle uptake inversely correlates with size. The influence of shape has not been reported. Surface charge has not been clearly shown to affect flux across the blood-brain barrier. There is very little evidence for metal-based nanoparticle distribution into brain parenchyma. Metal-based nanoparticle disruption of the blood-brain barrier and adverse brain changes have been shown, and are more pronounced for spheres than rods. Study concentrations need to be put in exposure contexts. Work with dorsal root ganglion cells and brain cells in vitro show the potential for metal-based nanoparticles to produce toxicity. Interpretation of these results must consider the ability of nanoparticles to distribute across the barriers protecting the nervous system. Effects of the persistence of poorly soluble metal-based nanoparticles are of particular concern.
- Published
- 2013
35. Biodistribution and biopersistence of ceria engineered nanomaterials: size dependence
- Author
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Peng Wu, Jason M. Unrine, Uschi M. Graham, Eric A. Grulke, Robert A. Yokel, Mo Dan, and Michael T. Tseng
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Biodistribution ,Materials science ,Engineered nanomaterials ,Central nervous system ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Spleen ,Rats, Sprague-Dawley ,Parenchyma ,medicine ,Animals ,Nanotechnology ,Scattering, Radiation ,Tissue Distribution ,General Materials Science ,Tissue distribution ,Particle Size ,Size dependence ,Cerium ,Nanostructures ,Rats ,Sprague dawley ,medicine.anatomical_structure ,Liver ,Molecular Medicine - Abstract
The aims were to determine the biodistribution, translocation, and persistence of nanoceria in the brain and selected peripheral organs. Nanoceria is being studied as an anti-oxidant therapeutic. Five, 15, 30, or 55 nm ceria was iv infused into rats which were terminated 1, 20, or 720 h later. Cerium was determined in blood, brain, liver, and spleen. Liver and spleen contained a large percentage of the dose, from which there was no significant clearance over 720 h, associated with adverse changes. Very little nanoceria entered brain parenchyma. The results suggest brain delivery of nanoceria will be a challenge. From the Clinical Editor This team of investigators revealed that nanoceria, which is being studied as an anti-oxidant, has very limited uptake by the brain regardless of the range of sizes studied, suggesting major challenges in the application of this novel approach in the central nervous system.
- Published
- 2013
36. Aluminum: Properties, Presence in Food and Beverages, Fate in Humans, and Determination
- Author
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Robert A. Yokel
- Subjects
inorganic chemicals ,Materials science ,food.ingredient ,Aqueous solution ,business.industry ,Food additive ,digestive, oral, and skin physiology ,Food storage ,chemistry.chemical_element ,Portable water purification ,complex mixtures ,food ,chemistry ,Elemental analysis ,Aluminium ,Food processing ,Food science ,Digestion ,business - Abstract
The chemical form of aluminum, influenced by pH, greatly influences its behavior. Aluminum is extensively used, in water purification, in personal care products, in medications, as food additives, and in beverage and food processing and storage. Food provides the major source of daily aluminum intake for most people, typically 5–10 mg. Consumption of food with aluminum-containing food additives can greatly increase this. Beverage and food processing and storage in aluminum vessels usually increase their aluminum content, constituting
- Published
- 2016
37. Aluminum: The Toxicology of
- Author
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Robert A. Yokel
- Subjects
inorganic chemicals ,Bone disease ,business.industry ,medicine.medical_treatment ,Lung fibrosis ,Developmental toxicity ,Cancer ,Disease ,medicine.disease ,complex mixtures ,Toxicology ,medicine.anatomical_structure ,Toxicity ,medicine ,Bone marrow ,business ,Adjuvant - Abstract
The safety versus toxicity of aluminum has been and is controversial. Aluminum-induced toxicity has been demonstrated in animals, usually using exposures well beyond those encountered by humans. Aluminum-induced toxicity to humans' brain, bone, and bone marrow can occur when it is introduced directly into the bloodstream, is in dialysis fluids, or is introduced into the brain or a body cavity in very large amounts. Aluminum welding and other airborne exposures can cause adverse neurobehavioral changes and lung fibrosis. Aluminum-induced reproductive system toxicity, embryotoxicity, teratogenicity, autism spectrum disorder, and cancer have not been convincingly shown. The safety of aluminum as an adjuvant in vaccines and its contribution to Alzheimer's disease are hotly debated topics for which there is no consensus.
- Published
- 2016
38. Influence of surface charge on lysozyme adsorption to ceria nanoparticles
- Author
-
Peng Wu, Eric A. Grulke, Binghui Wang, and Robert A. Yokel
- Subjects
Materials science ,Inorganic chemistry ,General Physics and Astronomy ,Nanoparticle ,Surfaces and Interfaces ,General Chemistry ,Condensed Matter Physics ,Surfaces, Coatings and Films ,Nanomaterials ,chemistry.chemical_compound ,Adsorption ,chemistry ,Chemical engineering ,Monolayer ,Surface modification ,Surface charge ,Lysozyme ,Protein adsorption - Abstract
Understanding mechanisms for forming protein coronas on nanomaterial surfaces is essential to designing drug delivery systems and designing and interpreting the results of nanomaterial toxicity tests. The study reports the adsorption behavior of a positively charged protein, lysozyme, on cerium dioxide (ceria) nanoparticles with three different surface charges. Adsorption isotherms were modeled with the Toth and Sips equations. Isotherm loading levels were compared to monolayer coverage estimate for ‘side-on’ and ‘end-on’ lysozyme orientations as well as random packing (jamming) and maximum packing limits. Evaluation of adsorption site energy distributions (generated using the model coefficients) suggested that the negatively charged ceria surface had a very broad site energy distribution and that its surface heterogeneity controls the adsorption process. By contrast, the adsorption of lysozyme on the positively charged nanoparticles appears to be influenced by lateral effects from adsorbed protein species. The results illustrate the importance of nanoparticle surface chemistry to protein adsorption. The modeling and site energy distribution evaluations may be useful for interpreting the formation of protein coronas on nanoparticles.
- Published
- 2012
39. The Pharmacokinetics and Toxicology of Aluminum in the Brain
- Author
-
Robert A. Yokel
- Subjects
inorganic chemicals ,Chemistry ,General Engineering ,Glutamate receptor ,Neurotoxicity ,Pharmacology ,Blood–brain barrier ,medicine.disease ,complex mixtures ,medicine.anatomical_structure ,Cerebrospinal fluid ,Toxicity ,Extracellular fluid ,Blood plasma ,medicine ,General Earth and Planetary Sciences ,Choroid plexus ,General Environmental Science - Abstract
The chemical forms (species) of aluminum in blood plasma and brain extracellular fluid are considered, as they are the candidates for brain aluminum uptake and efflux. The blood-brain barrier is the primary site of brain aluminum up- take. The mechanism of brain uptake of aluminum transferrin, long thought to be mediated by transferrin-receptor medi- ated endocytosis, requires further investigation. Brain Al citrate uptake has been attributed to the sodium-independent L- glutamate/L-cystine exchanger system, system Xc-. Reports have suggested aluminum can compromise blood-brain barrier in- tegrity, however the studies were conducted with aluminum concentrations greatly exceeding those seen in human blood plasma. Aluminum appeared in cerebrospinal fluid suggesting it can cross the choroid plexus and in brain after intranasal appli- cation suggesting it can be taken up by cranial nerves, but neither of these routes has been definitively demonstrated. Brain aluminum efflux appears to be carrier-mediated, however the mechanism has not been identified. A small increase in brain aluminum seems sufficient to produce neurotoxicity. Once aluminum enters the brain it persists there for a very long time; es- timates of the half-life range from 20% of the lifespan to greater than the lifespan. Al persistence in bone, which maintains the majority of the body burden, may influence brain Al, due to equilibrium among the body's organs. Chelation therapy with des- ferrioxamine has been shown to reduce some manifestations of aluminum toxicity although it may increase redistribution of aluminum to the brain to increase aluminum-induced neurotoxicity. An orally-effective aluminum chelator that is an improve- ment over desferrioxamine has not yet been demonstrated. Although a non-essential metal, there are mechanisms enabling aluminum to get into the brain, accumulating over the lifespan, and creating the potential to contribute to many neurodegenera- tive disorders.
- Published
- 2012
40. Physicochemical properties of engineered nanomaterials that influence their nervous system distribution and effects
- Author
-
Robert A. Yokel
- Subjects
0301 basic medicine ,Nervous system ,Chemistry ,Engineered nanomaterials ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Nanotechnology ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Nervous System ,Nanostructures ,03 medical and health sciences ,Surface coating ,030104 developmental biology ,medicine.anatomical_structure ,medicine ,Molecular Medicine ,Distribution (pharmacology) ,Humans ,General Materials Science ,Tissue Distribution ,Tissue distribution ,0210 nano-technology - Abstract
This critical review examines in vitro and in vivo evidence for the influence of engineered nanomaterial (ENM) physicochemical properties on their distribution into, and effects on, the nervous system. Nervous system applications of ENMs; exposure routes and potential for uptake; the nervous system and its barriers to ENM uptake; and the mechanisms of uptake into the nervous system and overcoming those barriers are summarized. The findings of English-language publications of studies that included at least two variations of an ENM physicochemical property and reported results of their pharmacokinetic and/or pharmacodynamic interaction with the nervous system that differed as a function of ENM physicochemical property(ies) are summarized in Supplementary Materials. A summary conclusion is drawn for each of the physicochemical properties on the strength of the evidence that it influences ENM-nervous system interaction.
- Published
- 2015
41. Manganese Flux Across the Blood–Brain Barrier
- Author
-
Robert A. Yokel
- Subjects
ATPase ,chemistry.chemical_element ,Calcium ,Blood–brain barrier ,Mice ,Cellular and Molecular Neuroscience ,ATP hydrolysis ,medicine ,Animals ,Humans ,Cation Transport Proteins ,Manganese ,biology ,Chemistry ,Calcium channel ,Neurotoxicity ,Metabolism ,medicine.disease ,Mitochondria ,Rats ,Trace Elements ,medicine.anatomical_structure ,Neurology ,Biochemistry ,Blood-Brain Barrier ,biology.protein ,Molecular Medicine ,Female ,Calcium Channels ,Efflux - Abstract
Manganese (Mn) is essential for brain growth and metabolism, but in excess can be a neurotoxicant. The chemical form (species) of Mn influences its kinetics and toxicity. Significant Mn species entering the brain are the Mn(2+) ion and Mn citrate which, along with Mn transferrin, enter the brain by carrier-mediated processes. Although the divalent metal transporter (DMT-1) was suggested to be a candidate for brain Mn uptake, brain Mn influx was not different in Belgrade rats, which do not express functional DMT-1, compared to controls. Brain Mn influx was not sodium dependent or dependent on ATP hydrolysis, but was reduced by mitochondrial energy inhibitors. Mn and Fe do not appear to compete for brain uptake. Brain Mn uptake appears to be mediated by a Ca uptake mechanism, thought to not be a p-type ATPase, but a store-operated calcium channel. Efflux of Mn from the brain was found to be slower than markers used as membrane impermeable reference compounds, suggesting diffusion mediates brain Mn efflux. Owing to carrier-mediated brain Mn influx and diffusion-mediated efflux, slow brain Mn clearance and brain Mn accumulation with repeated excess exposure would be predicted, and have been reported. This may render the brain susceptible to Mn-induced neurotoxicity from excessive Mn exposure.
- Published
- 2009
42. Biodistribution and oxidative stress effects of a systemically-introduced commercial ceria engineered nanomaterial
- Author
-
Uschi M. Graham, Michael T. Tseng, D. Allan Butterfield, Peng Wu, Rebecca L. Florence, Jason M. Unrine, Robert A. Yokel, Sarita S. Hardas, Eric A. Grulke, and Rukhsana Sultana
- Subjects
Biodistribution ,Materials science ,Biomedical Engineering ,Neurotoxicity ,Spleen ,Mononuclear phagocyte system ,Toxicology ,medicine.disease_cause ,medicine.disease ,Blood–brain barrier ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Biochemistry ,medicine ,Biophysics ,Fluorescein ,Oxidative stress ,Evans Blue - Abstract
The objective was to characterize the biodistribution of nanoscale ceria from blood and its effects on oxidative stress endpoints. A commercial 5% crystalline ceria dispersion in water (average particle size ~31±4 nm) was infused intravenously into rats (0, 50, 250 and 750 mg/kg), which were terminated 1 or 20 h later. Biodistribution in rat tissues was assessed by microscopy and ICP-AES/MS. Oxidative stress effects were assessed by protein-bound 4-hydroxy 2-trans-nonenal (HNE), protein-bound 3-nitrotyrosine (3-NT), and protein carbonyls. Evans blue (EB)-albumin and Na fluorescein (Na2F) were given intravenously as blood-brain barrier integrity markers. The initial ceria t½ in blood was ~7 min. Brain EB and Na2F increased some at 20 h. Microscopy revealed peripheral organ ceria agglomerations but little in the brain. Spleen Ce concentration was >liver >blood >brain. Reticuloendothelial tissues cleared ceria. HNE was significantly increased in the hippocampus at 20 h. Protein carbonyl and 3-NT changes were...
- Published
- 2009
43. Aluminum bioavailability from tea infusion
- Author
-
Rebecca L. Florence and Robert A. Yokel
- Subjects
Male ,Food intake ,Biological Availability ,Toxicology ,Systemic circulation ,Article ,Pharmacokinetics ,Animals ,Food science ,Salp ,Radioisotopes ,Tea ,biology ,Chemistry ,Spectrophotometry, Atomic ,General Medicine ,biology.organism_classification ,Rats, Inbred F344 ,Rats ,Bioavailability ,Data Interpretation, Statistical ,Environmental chemistry ,Sodium aluminum phosphate ,Toxicity ,Dietary Proteins ,Perfusion ,Aluminum ,Food Science - Abstract
The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer (26)Al. (26)Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous (27)Al infusion. Oral Al bioavailability (F) was calculated from the area under the (26)Al, compared to (27)Al, serum concentration x time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F=0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F=0.1-0.3%), but greater than acidic SALP in a biscuit (F=0.1%). Time to maximum serum (26)Al concentration was 1.25, 1.5, 8 and 4.8h, respectively. These results of oral Al bioavailability x daily consumption by the human suggest tea can provide a significant amount of the Al that reaches systemic circulation. This can allow distribution to its target organs of toxicity, the central nervous, skeletal and hematopoietic systems. Further testing of the hypothesis that Al contributes to Alzheimer's disease may be more warranted with studies focusing on total average daily food intake, including tea and other foods containing appreciable Al, than drinking water.
- Published
- 2008
44. Aluminium Toxicokinetics: An Updated MiniReview
- Author
-
Patrick J. McNamara and Robert A. Yokel
- Subjects
Pharmacology ,chemistry ,business.industry ,Aluminium ,Health, Toxicology and Mutagenesis ,Environmental chemistry ,Medicine ,Toxicokinetics ,chemistry.chemical_element ,Toxicology ,business - Published
- 2008
45. Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese
- Author
-
Robert A. Yokel, C.L. Hicks, and Rebecca L. Florence
- Subjects
Male ,Absorption (pharmacology) ,food.ingredient ,Sodium ,Biological Availability ,chemistry.chemical_element ,Toxicology ,Systemic circulation ,Mass Spectrometry ,Article ,Phosphates ,food ,Pharmacokinetics ,Cheese ,Animals ,Food science ,Aluminum Compounds ,Salp ,Radioisotopes ,biology ,Spectrophotometry, Atomic ,Food additive ,General Medicine ,biology.organism_classification ,Sodium Compounds ,Rats, Inbred F344 ,Rats ,Bioavailability ,chemistry ,Area Under Curve ,Data Interpretation, Statistical ,Emulsifying Agents ,Sodium aluminum phosphate ,Environmental chemistry ,Food Additives ,Aluminum ,Food Science - Abstract
Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability results were intermediate to previously reported results from drinking water (F approximately 0.3%) and acidic-SALP incorporated into a biscuit (F approximately 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human's daily Al intake ( approximately 95% and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.
- Published
- 2008
46. Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells
- Author
-
Sanjit K. Dhar, Robert A. Yokel, Rebecca L. Florence, Vasudevan Bakthavatchalu, Peng Wu, Yumin Chen, Eric A. Grulke, Michael T. Tseng, Daret K. St. Clair, Hsin-Sheng Yang, and Swatee Dey
- Subjects
Cancer Research ,bcl-X Protein ,Apoptosis ,Superoxide dismutase ,Mice ,Sirtuin 1 ,Proliferating Cell Nuclear Antigen ,Aluminum Oxide ,Animals ,Sirtuins ,Neoplastic transformation ,Viability assay ,Cancer Biology ,Cell Proliferation ,Skin ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Superoxide Dismutase ,Cell growth ,Activator (genetics) ,Epithelial Cells ,General Medicine ,Cell biology ,Proliferating cell nuclear antigen ,Transcription Factor AP-1 ,Cell Transformation, Neoplastic ,chemistry ,Biochemistry ,Carcinogens ,biology.protein ,Nanoparticles ,Reactive Oxygen Species - Abstract
The physicochemical properties of nanomaterials differ from those of the bulk material of the same composition. However, little is known about the underlying effects of these particles in carcinogenesis. The purpose of this study was to determine the mechanisms involved in the carcinogenic properties of nanoparticles using aluminum oxide (Al(2)O(3)/alumina) nanoparticles as the prototype. Well-established mouse epithelial JB6 cells, sensitive to neoplastic transformation, were used as the experimental model. We demonstrate that alumina was internalized and maintained its physicochemical composition inside the cells. Alumina increased cell proliferation (53%), proliferating cell nuclear antigen (PCNA) levels, cell viability and growth in soft agar. The level of manganese superoxide dismutase, a key mitochondrial antioxidant enzyme, was elevated, suggesting a redox signaling event. In addition, the levels of reactive oxygen species and the activities of the redox sensitive transcription factor activator protein-1 (AP-1) and a longevity-related protein, sirtuin 1 (SIRT1), were increased. SIRT1 knockdown reduces DNA synthesis, cell viability, PCNA levels, AP-1 transcriptional activity and protein levels of its targets, JunD, c-Jun and BcL-xl, more than controls do. Immunoprecipitation studies revealed that SIRT1 interacts with the AP-1 components c-Jun and JunD but not with c-Fos. The results identify SIRT1 as an AP-1 modulator and suggest a novel mechanism by which alumina nanoparticles may function as a potential carcinogen.
- Published
- 2008
47. Evaluation of 1-methyl-3,4-hydroxypyridinecarboxylic acids as possible bidentate chelating agents for iron(III): Metal–ligand solution chemistry
- Author
-
Haitao Li, Annalisa Dean, Valerio Di Marco, Robert A. Yokel, and G. Giorgio Bombi
- Subjects
Denticity ,Aqueous solution ,chelation therapy ,medicine.diagnostic_test ,Chemistry ,Ligand ,Inorganic chemistry ,Potentiometric titration ,iron ,Carboxylate ligands ,potentiometry ,UV-Vis ,solution chemistry ,Inorganic Chemistry ,Metal ,Spectrophotometry ,visual_art ,Materials Chemistry ,medicine ,visual_art.visual_art_medium ,Chelation ,Physical and Theoretical Chemistry ,Stoichiometry - Abstract
The chemical interactions of 1-methyl-3-hydroxy-4-pyridinecarboxylic acid (1M3H4P) and 1-methyl-4-hydroxy-3-pyridinecarboxylic acid (1M4H3P) with Fe(III) were investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations and UV–Vis spectrophotometry. A large number of complexes were formed in solution with stoichiometry FeL x H y , x = 1, 2, 3 and y = 0, −1, −2. In view of a possible application to Fe(III) chelation therapy, the efficiencies of the ligands to chelate the metal ion were evaluated in vitro at physiological pH. 1M3H4P and 1M4H3P show a lower complexation efficiency with Fe(III) than that of other available chelators, but higher than that of their non-methylated analogs 3H4P and 4H3P.
- Published
- 2007
48. In Vivo Processing of Ceria Nanoparticles inside Liver: Impact on Free-Radical Scavenging Activity and Oxidative Stress
- Author
-
Alan Dozier, Eric A. Grulke, D. Allan Butterfield, Jason M. Unrine, Sarita S. Hardas, Rukhsana Sultana, Burtron H. Davis, Uschi M. Graham, Michael T. Tseng, Jacek B. Jasinski, and Robert A. Yokel
- Subjects
Free Radical Scavenging Activity ,Chemistry ,Nanoparticle ,Nanotechnology ,General Chemistry ,medicine.disease_cause ,Redox ,Article ,In vivo ,Biophysics ,medicine ,Solubility ,Cytotoxicity ,Oxidative stress - Abstract
The cytotoxicity of ceria ultimately lies in its electronic structure, which is defined by the crystal structure, composition, and size. Despite previous studies focused on ceria uptake, distribution, biopersistance, and cellular effects, little is known about its chemical and structural stability and solubility once sequestered inside the liver. Mechanisms will be presented that elucidate the in vivo transformation in the liver. In vivo processed ceria reveals a particle-size effect towards the formation of ultrafines, which represent a second generation of ceria. A measurable change in the valence reduction of the second-generation ceria can be linked to an increased free-radical scavenging potential. The in vivo processing of the ceria nanoparticles in the liver occurs in temporal relation to the brain cellular and protein clearance responses that stem from the ceria uptake. This information is critical to establish a possible link between cellular processes and the observed in vivo transformation of ceria. The temporal linkage between the reversal of the pro-oxidant effect (brain) and ceria transformation (liver) suggests a cause-effect relationship.
- Published
- 2015
49. Aluminum
- Author
-
Robert A. Yokel, Bengt Sjögren, Anders Iregren, and Johan Montelius
- Subjects
inorganic chemicals ,Gastrointestinal tract ,Inhalation ,business.industry ,Developmental toxicity ,Physiology ,Urine ,Dialysis Encephalopathy ,medicine.disease ,complex mixtures ,Excretion ,Aluminum can ,Pulmonary fibrosis ,medicine ,business - Abstract
Aluminum is ubiquitous in the environment. Its proportion of the Earth’s crust is about 8%. Aluminum can be absorbed from the gastrointestinal tract and from the lungs. Excretion is mainly through the kidneys, probably as aluminum citrate. Aluminum is a well-known neurotoxicant. Significant accumulation in the human body has been related to the presence of aluminum in dialysis fluids and the concomitant intake of aluminum-containing drugs by those with significant renal impairment and to occupational exposure in some industrial settings. Accumulation in patients with renal impairment has resulted in dialysis encephalopathy that was often fatal; this problem is now well recognized and usually avoided. Neurotoxic effects have been observed in welders with aluminum urine concentrations around 100 μg/L. The upper reference limit among nonexposed individuals is 16 μg/L urine. There is no consensus on whether human studies provide sufficient evidence for an association between aluminum and Alzheimer disease. Occupational exposure to aluminum powder has resulted in pulmonary fibrosis. Asthma has been associated with the inhalation of aluminum sulfate, aluminum fluoride, and potassium aluminum tetrafluoride, and exposure to the complex environment in potrooms during electrolytic aluminum production. Cancer and ischemic heart disease have been observed among aluminum production workers. However, it is unlikely that aluminum is the cause of these diseases. Reproductive and developmental toxicity are presented in Chapter 20. Recent reviews on aluminum were written by Krewski et al. (2007), Riihimaki and Aitio (2012), Willhite et al. (2012), DECOS (2010), and NEG (2011).
- Published
- 2015
50. List of Contributors
- Author
-
Jan Aaseth, Peter Aggett, Antero Aitio, Jan Alexander, Shegufta Ameer, Christian B.I. Andersen, Ole Andersen, Pietro Apostoli, Michael Aschner, Farida Louise Assem, Lars Barregård, David C. Bellinger, Ingvar A. Bergdahl, Maths Berlin, Balázs Berlinger, Alfred Bernard, Carolina Bigert, Poul Bjerregaard, Robyn Blain, Karin Broberg, Jason Brocato, Ronald P. Brown, Esben Budtz-Jørgensen, Samuel W. Caito, Simona Catalani, C.-J. Chen, C.-H. Selene, J. Chou, Max Costa, Todd Davidson, John W. Eaton, Alison Elder, Carl -Gustaf Elinder, Dag G. Ellingsen, Hisham A. El-Masri, Karin Engström, Bengt Fadeel, Obaid M. Faroon, Bruce A. Fowler, Silvia Fustinoni, Lars Gerhardsson, Philippe Grandjean, Per Gustavsson, James S. Holler, Per Hultman, Ivo Iavicoli, Anders Iregren, Marek Jakubowski, Taiyi Jin, Robert L. Jones, Hanna L. Karlsson, George Kazantzis, Qindong Ke, Larry S. Keith, Mirja Kiilunen, Yangho Kim, Catherine Klein, Michael Kleinman, David Kotelchuck, Yukinori Kusaka, Philip J. Landrigan, Sverre Langård, Freda Laulicht, Per E. Leffler, Veruscka Leso, Dominique Lison, Roberto G. Lucchini, Nikki Maples-Reynolds, Daphne B. Moffett, Lisbeth Birk Møller, Johan Montelius, Moiz M. Mumtaz, Koji Nogawa, Gunnar F. Nordberg, Monica Nordberg, Agneta Oskarsson, Elena A. Ostrakhovich, Cezary PałczyŃski, K. Michael Pollard, Prem Ponka, Candace M. Prusiewicz, Patricia Ruiz, Harold H. Sandstead, Tiina Santonen, Marko ŠariĆ, Kazuhiro Sato, Hiroshi Satoh, Mary J. Sexton, Bengt Sjögren, Staffan Skerfving, Donald R. Smith, Dexter W. Sullivan, Jonas Tallkvist, Milton Tenenbein, Muhammet S. Toprak, Carolyn Tylenda, Tomohiro Umemura, Richard P. Wedeen, Robert A. Yokel, and Rudolfs K. Zalups
- Published
- 2015
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