Effect on Mouse Liver Morphology of CeO2, TiO2 and Carbon Black Nanoparticles Translocated from Lungs or Deposited Intravenously

Exposure to nanoparticles by various routes results in size-dependent translocation of nanoparticles to the systemic circulation and subsequent accumulation in the liver. The purpose of this study was to determine possible adverse effects in the liver of long-lasting nanoparticle presence in the organ. Mice exposed to a single dose (162 µg/animal equivalent to 9 mg/kg body weight) of TiO2, CeO2 or carbon black nanoparticles by intratracheal instillation or intravenous injection, resulting in relatively low or high liver burdens, were followed for 1, 28 or 180 days. Clinical appearance, feed intake, body and liver weights, hematological indices, and transaminases and alkaline phosphatase activities were unaffected by exposure. Exposure-related foreign material persisted in the liver up to 180 days after intratracheal and intravenous exposure, mainly in sinusoids, near Kupffer cells, or around blood vessels. Increased incidences of histological findings after intratracheal or intravenous exposure included: initially, prominent nuclei of Kupffer cells, the apparent increase in binucleate hepatocytes (TiO2 and carbon black) and inflammatory infiltrations (CeO2); later, cytoplasmic vacuolation, pyknosis and necrosis, especially for CeO2. Thus, neither low nor high nanoparticle burden in the liver affected enzymatic markers of liver injury, but indications of exposure-related necrotic changes, particularly for CeO2 nanoparticles, were noted.

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Exposure to carbon black nanoparticles during pregnancy aggravates lipopolysaccharide-induced lung injury in offspring: an intergenerational effect

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00545.2020 ◽

2021 ◽

Author(s):

Qianghu Tang ◽

Baijie Tu ◽

Xuejun Jiang ◽

Jun Zhang ◽

Lulu Bai ◽

...

Keyword(s):

Lung Injury ◽

Carbon Black ◽

Intratracheal Instillation ◽

Dna Methyltransferases ◽

Dna Hypermethylation ◽

Carbon Black Nanoparticles ◽

Pregnant Mice ◽

Mock Treatment ◽

Intergenerational Effect ◽

First Time

Carbon black nanoparticles (CBNPs) are one of the most frequently used nanoparticles. Exposure to CBNPs during pregnancy (PrE to CBNPs) can directly induce inflammation, lung injury and genotoxicity in dams, and results in abnormalities in offspring. However, whether exposure to CBNPs during pregnancy enhances the susceptibility of offspring to environmental stimuli remains unknown. To address this issue, in this study, we intranasally treated pregnant mice with mock or CBNPs from gestational day (GD) 9 to GD18, and F1 and F2 offspring were normally obtained. By intratracheal instillation of mice with lipopolysaccharide (LPS) to trigger a classic animal model for acute lung injury, we intriguingly found that after LPS treatment, F1 and F2 offspring after exposure during pregnancy to CBNPs both exhibited more pronounced lung injury symptoms, including more degenerative histopathological changes, vascular leakage, elevated MPO activity and activation of inflammation-related signaling transduction, compared to F1 and F2 offspring in the mock treatment group, suggesting PrE to CBNPs would aggravate LPS-induced lung injury in offspring, and this effect is intergenerational. We also observed that PrE to CBNPs upregulated the mRNA expression of DNA methyltransferases (Dnmt) 1/3a/3b and DNA hypermethylation in both F1 and F2 offspring, which might partially account for the intergenerational effect. Together, our study demonstrates for the first time that PrE to CBNPs can enhance sensitivity to LPS in both F1 and F2 offspring, and this intergenerational effect may be related to DNA hypermethylation caused by CBNPs.

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