Dataset Information

Consequent stages of developing a multi-compartmental mechanistic model for chronically inhaled nanoparticles pulmonary retention.

ABSTRACT: The paper retraces the development of a mechanistic multicompartmental system model describing particle retention in lungs under chronic inhalation exposures. This model was first developed and experimentally tested for various conditions of exposure to polydisperse dusts of SiO₂ or TiO₂. Later on it was successfully used as a basis for analyzing patterns in the retention of nanoparticles having different chemical compositions (Fe₂O₃, SiO₂, NiO). This is the first publication presenting the outcomes of modeling lung retention of nickel oxide nano-aerosols under chronic inhalation exposure. The most significant adaptation of the above-mentioned model to the conditions of exposure to metal-oxide nanoparticles is associated with the need to describe mathematically not only the physiological mechanisms of their elimination but also their solubilization "in vivo" bearing in mind that the relative contribution of the latter may be different for nanoparticles of different nature and predominant in some cases. Using nickel oxide as an example, it is suggested as well that damage to the physiological pulmonary clearance mechanisms by particularly toxic nanoparticles may result in lung toxicokinetics becoming nonlinear.

SUBMITTER: Katsnelson BA

PROVIDER: S-EPMC6446054 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Consequent stages of developing a multi-compartmental mechanistic model for chronically inhaled nanoparticles pulmonary retention.

Katsnelson Boris A BA Sutunkova Marina P MP Konysheva Ludmila K LK Solovyeva Svetlana N SN Minigalieva Ilzira A IA Gurvich Vladimir B VB Privalova Larissa I LI

Toxicology reports 20190327

The paper retraces the development of a mechanistic multicompartmental system model describing particle retention in lungs under chronic inhalation exposures. This model was first developed and experimentally tested for various conditions of exposure to polydisperse dusts of SiO2 or TiO2. Later on it was successfully used as a basis for analyzing patterns in the retention of nanoparticles having different chemical compositions (Fe2O3, SiO2, ...[more]

PMID: 30984565

Similar Datasets

Project description:Pulmonary exposure to high doses of nanoparticles (NP) leads to well characterized lung toxicity in addition to long-term NP retention. However, pulmonary NP accumulation and toxicity following low dose exposures are not well described. In the present study we sought to: (1) investigate particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2) and (2) determine the effects of long-term particle accumulation on pulmonary systems. Female C57BL/6 mice were exposed to rutile nano-TiO2 (primary size of 20.6 nm and surface area of 107.7 m2/g) via single intratracheal instillations of 18, 54 and 162 M-BM-5g/mouse and sampled 1, 3 and 28 days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using Nanoscale Hyperspectral Microscope. DNA microarrays, pathway-specific real-time RT-PCR (qPCR) and gene-specific qPCR arrays, and tissue protein analyses were employed to characterize pulmonary responses. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28 days post-exposure time. Retention did not correlate with the extent of inflammatory neutrophil influx into the lungs. DNA microarray analysis showed altered expression of approximately 3000 genes across all treatment groups (M-BM-11.3 fold; p<0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein levels. Although the low dose exposure failed to induce observable inflammation, significant changes in the expression of genes and proteins associated with inflammation were observed. Moreover, diminished (or absent) neutrophil influx in the low and medium dose groups was correlated with negative regulation of genes associated with ion homeostasis and muscle regulation. Gene expression changes for several inflammatory mediators have previously been noted in mice exposed to the same nano-TiO2 via inhalation. Our results suggest that retention of nano-TiO2 in the absence of inflammation and effective clearance can perturb calcium and ion homeostasis, and affect smooth muscle activities over time. This experiment consists of three different dosages of TiO2, e.g., low (18 ug), medium (54 ug) and high (162 ug), and one control. There are 3 time points for each treatment and control group, e.g., day 1, day 3 and day 28. Each dose or time point has 5-6 biological replicates. There are total 65 samples (arrays)

Project description:Pulmonary exposure to high doses of nanoparticles (NP) leads to well characterized lung toxicity in addition to long-term NP retention. However, pulmonary NP accumulation and toxicity following low dose exposures are not well described. In the present study we sought to: (1) investigate particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2) and (2) determine the effects of long-term particle accumulation on pulmonary systems. Female C57BL/6 mice were exposed to rutile nano-TiO2 (primary size of 20.6 nm and surface area of 107.7 m2/g) via single intratracheal instillations of 18, 54 and 162 µg/mouse and sampled 1, 3 and 28 days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using Nanoscale Hyperspectral Microscope. DNA microarrays, pathway-specific real-time RT-PCR (qPCR) and gene-specific qPCR arrays, and tissue protein analyses were employed to characterize pulmonary responses. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28 days post-exposure time. Retention did not correlate with the extent of inflammatory neutrophil influx into the lungs. DNA microarray analysis showed altered expression of approximately 3000 genes across all treatment groups (±1.3 fold; p<0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein levels. Although the low dose exposure failed to induce observable inflammation, significant changes in the expression of genes and proteins associated with inflammation were observed. Moreover, diminished (or absent) neutrophil influx in the low and medium dose groups was correlated with negative regulation of genes associated with ion homeostasis and muscle regulation. Gene expression changes for several inflammatory mediators have previously been noted in mice exposed to the same nano-TiO2 via inhalation. Our results suggest that retention of nano-TiO2 in the absence of inflammation and effective clearance can perturb calcium and ion homeostasis, and affect smooth muscle activities over time.

Dataset Information

Consequent stages of developing a multi-compartmental mechanistic model for chronically inhaled nanoparticles pulmonary retention.

Publications

Consequent stages of developing a multi-compartmental mechanistic model for chronically inhaled nanoparticles pulmonary retention.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets