Dataset Information

Nanoceria distribution and effects are mouse-strain dependent.

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 10 mg/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.

SUBMITTER: Yokel RA

PROVIDER: S-EPMC8496957 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:EXPERIMENT: Microarray expression profiles derived from the cranial neural folds (headfold) of neurulation-stage mouse embryos 3.0h after maternal alcohol exposure on 8 d.p.c. ANIMAL MODEL: Pregnancies from 2 substrains of C57BL/6 mice that differ in relative risk of Fetal Alcohol Syndrome (FAS): C57BL/6J (B6J) high-risk condition, and C57BL/6NCrl (B6N) low-risk condition. EXPOSURE: Dams dosed with ethanol (EtOH) by intraperitoneal injection at 2.9 g EtOH per kg body weight. Controls received vehicle (saline) alone. A third group of dams received EtOH + 4.0 mg/kg PK11195, a specific high-affinity ligand to the 18 KDa mitochondrial peripheral benzodiazepine receptor site. INTERVAL: High blood alcohol content must be sustained in dams for several hours to invoke FAS and is traditionally accomplished by a double injection of EtOH 4.0h apart. Since these embryos were harvested for genetic analysis 1h before dams would have gotten the second alcohol injection, the interval represents a snapshot of the critical response, prior to the second maternal injection that invokes greater risk. Counter-exposure to PK11195 significantly lowers the adverse response of B6J embryos to EtOH. PLATFORM: Two independent assays run. The first dataset (PE), run April 2002 – January 2003, used samples pooled from 2 litters (PE) and the platform was a two-channel MPS621 array (http://www.lifesciences.perkinelmer.com/). This platform has 4800 sequence-verified gene elements derived from over 50 different human cDNA libraries reflecting a variety of well-annotated cellular processes and disease pathways. The second dataset (AF), run between May 2005 – November 2005, used samples pooled from 1 litter and the platform was Affymetrix GeneChip® Mouse Genome 430A 2.0 Array (http://www.affymetrix.com/). The MG430A 2.0 platform has 45,102 oligonucleotide probe cells representing approximately 14,000 well-characterized genes in the draft mouse genome assembly. The corresponding GEO samples are GSM12218 - GSM12227 for the two-channel PE arrays, and GSM136067 - GSM136078 for the one-channel AF arrays. Keywords = fetal alcohol syndrome Keywords = alcohol-related birth defects Keywords = EtOH Keywords = PK11195 Keywords = embryo Keywords = strain differences Keywords: Ordered

Project description:EXPERIMENT: Microarray expression profiles derived from the cranial neural folds (headfold) of neurulation-stage mouse embryos 3.0h after maternal alcohol exposure on 8 d.p.c. ANIMAL MODEL: Pregnancies from 2 substrains of C57BL/6 mice that differ in relative risk of Fetal Alcohol Syndrome (FAS): C57BL/6J (B6J) high-risk condition, and C57BL/6NCrl (B6N) low-risk condition. EXPOSURE: Dams dosed with ethanol (EtOH) by intraperitoneal injection at 2.9 g EtOH per kg body weight. Controls received vehicle (saline) alone. A third group of dams received EtOH + 4.0 mg/kg PK11195, a specific high-affinity ligand to the 18 KDa mitochondrial peripheral benzodiazepine receptor site. INTERVAL: High blood alcohol content must be sustained in dams for several hours to invoke FAS and is traditionally accomplished by a double injection of EtOH 4.0h apart. Since these embryos were harvested for genetic analysis 1h before dams would have gotten the second alcohol injection, the interval represents a snapshot of the critical response, prior to the second maternal injection that invokes greater risk. Counter-exposure to PK11195 significantly lowers the adverse response of B6J embryos to EtOH. PLATFORM: Two independent assays run. The first dataset (PE), run April 2002 â January 2003, used samples pooled from 2 litters (PE) and the platform was a two-channel MPS621 array (http://www.lifesciences.perkinelmer.com/). This platform has 4800 sequence-verified gene elements derived from over 50 different human cDNA libraries reflecting a variety of well-annotated cellular processes and disease pathways. The second dataset (AF), run between May 2005 â November 2005, used samples pooled from 1 litter and the platform was Affymetrix GeneChipÂ® Mouse Genome 430A 2.0 Array (http://www.affymetrix.com/). The MG430A 2.0 platform has 45,102 oligonucleotide probe cells representing approximately 14,000 well-characterized genes in the draft mouse genome assembly. The corresponding GEO samples are GSM12218 - GSM12227 for the two-channel PE arrays, and GSM136067 - GSM136078 for the one-channel AF arrays. Keywords = fetal alcohol syndrome Keywords = alcohol-related birth defects Keywords = EtOH Keywords = PK11195 Keywords = embryo Keywords = strain differences Keywords: Ordered Assay of early mouse embryos during pathogenesis of Fetal Alcohol Syndrome (FAS). Replicate RNA samples were arrayed by one-channel oligonucleotide (Affymetrix) or two-channel cDNA (Perkin-Elmer) platforms.

Project description:This critical review evolved from a SNO Special Workshop on Nanoceria panel presentation addressing the toxicological risks of nanoceria: accumulation, target organs, and issues of clearance; how exposure dose/concentration, exposure route, and experimental preparation/model influence the different reported effects of nanoceria; and how can safer by design concepts be applied to nanoceria? It focuses on the most relevant routes of human nanoceria exposure and uptake, disposition, persistence, and resultant adverse effects. The pulmonary, oral, dermal, and topical ocular exposure routes are addressed as well as the intravenous route, as the latter provides a reference for the pharmacokinetic fate of nanoceria once introduced into blood. Nanoceria reaching the blood is primarily distributed to mononuclear phagocytic system organs. Available data suggest nanoceria's distribution is not greatly affected by dose, shape, or dosing schedule. Significant attention has been paid to the inhalation exposure route. Nanoceria distribution from the lung to the rest of the body is less than 1% of the deposited dose, and from the gastrointestinal tract even less. Intracellular nanoceria and organ burdens persist for at least months, suggesting very slow clearance rates. The acute toxicity of nanoceria is very low. However, large/accumulated doses produce granuloma in the lung and liver, and fibrosis in the lung. Toxicity, including genotoxicity, increases with exposure time; the effects disappear slowly, possibly due to nanoceria's biopersistence. Nanoceria may exert toxicity through oxidative stress. Adverse effects seen at sites distal to exposure may be due to nanoceria translocation or released biomolecules. An example is elevated oxidative stress indicators in the brain, in the absence of appreciable brain nanoceria. Nanoceria may change its nature in biological environments and cause changes in biological molecules. Increased toxicity has been related to greater surface Ce3+, which becomes more relevant as particle size decreases and the ratio of surface area to volume increases. Given its biopersistence and resulting increased toxicity with time, there is a risk that long-term exposure to low nanoceria levels may eventually lead to adverse health effects. This critical review provides recommendations for research to resolve some of the many unknowns of nanoceria's fate and adverse effects.

Dataset Information

Nanoceria distribution and effects are mouse-strain dependent.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets