Comparison of single or multiple intratracheal administration for pulmonary toxic responses of nickel oxide nanoparticles in rats

Senoh, Hideki; Kano, Hirokazu; Suzuki, Michitaka; Ohnishi, Makoto; Kondo, Hitomi; Takanobu, Kenji; Umeda, Yumi; Aiso, Shigetoshi; Fukushima, Shoji

doi:10.1539/joh.16-0184-oa

Cited by 20 publications

(20 citation statements)

References 19 publications

(36 reference statements)

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“…Obviously, histological examination of lung tissues showed no significant differences between the multiple pulmonary administrations (3 times) and the single pulmonary treatment. Our results were in agreement with the previous report on single or multiple intratracheal administration for pulmonary toxic responses to nanoparticles in rats, clarifying that the single pulmonary administration was acceptable for the assessment of toxicity attributes concerning the histological examination of lung tissues . An increase of inflammation mediators in BALF indicated that the inhaled LPS might induce inflammation and lead to the secretion of proinflammatory molecules such as chemotactic cytokines and cell adhesion molecules in the lungs.…”

supporting

confidence: 92%

Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

Lin

Kankala

Tang

et al. 2018

Adv Healthcare Materials

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Pulmonary delivery of therapeutic agents has attracted increasing attention in biomedicine, as the lung is suitable to absorb large amounts of drugs due to its unique physiological characteristics, such as the high surface area (≈100 m 2 ), receipt of the entire cardiac output, thin blood-alveolar barrier, and low enzyme activity, among others. [1] In a way, insulin (INS) delivery through inhalation has been effective and well-tolerated, and provides significant glycemic control compared to the conventional, frequently administered, and invasive subcutaneous regimens. For example, Exubera was the first dry powder-based inhalation formulation of INS approved by the Pulmonary delivery of drugs has attracted increasing attention in healthcare, as the lungs are an easily accessible site for noninvasive systemic delivery of drugs. Although pulmonary inhalation of porous microparticles has been shown to sustain drug delivery, there are limited reports on efficient delivery of insulin and inhalation therapy of diabetes based on supercritical carbon dioxide (SC-CO 2 ) technology. Herein, this study reports the fabrication of insulin-loaded poly-l-lactide porous microspheres (INS-PLLA PMs) by using the SC-CO 2 technology, and their use as an inhalation delivery system potentially for diabetes therapy. Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are investigated. The PLLA PMs show negligible toxicity to lung-derived cells, resulting in no significant reduction in cell viability, as well as levels of various inflammatory mediators such as interleukin (IL)-6, IL-8, and tumor necrosis factor-α, compared with the negative control group. INS-PLLA PMs are further efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats. Together, the results demonstrate that the INS-PLLA PMs have a strong potential as an effective strategy for inhalation treatment of diabetes. Insulin Delivery

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supporting

confidence: 92%

Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

Lin

Kankala

Tang

et al. 2018

Adv Healthcare Materials

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“…Pure water has been used in previous intratracheal instillation studies 9,15,[23][24][25][26] . In the present study, while there were no notable increases in inflammatory cells or clinical markers in the BALF of rats administered pure water, intratracheal instillation of pure water induced eosinophilic infiltration in the interstitial area.…”

Section: Discussionmentioning

confidence: 99%

“…Recent toxicity studies of a variety of engineered nanomaterials have been performed using intratracheal instillation as the administration method [7][8][9][10][11][12] . The toxicity of nanomaterials depends on their size, shape, and surface properties 13 .…”

Section: Introductionmentioning

confidence: 99%

Effects of administering different vehicles via single intratracheal instillation on responses in the lung and pleural cavity of Crl:CD(SD) rats

Numano¹,

Morioka²,

Higuchi³

et al. 2020

J Toxicol Pathol

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Intratracheal instillation is the introduction of a substance directly into the trachea. Intratracheal instillation has been used to investigate the lung toxicity of several chemicals and requires the suspension or dissolution of test material in a vehicle for even dispersal throughout the lung. Importantly, the toxicities of vehicles used in intratracheal instillation studies are generally considered to be insignificant. Hence, evaluating the influence of different vehicles on the lung due to intratracheal instillation is crucial. We examined the toxic effects of pure water, saline, phosphate buffered saline (PBS), 0.5% Kolliphor ® P188 (KP188), 0.1% Tween 20 in saline, and 1.0% BSA in PBS. These vehicles were administered to male Crl:CD(SD) rats by a single intratracheal instillation. On day 3, broncho-alveolar lavage fluid (BALF) from the right lung was collected and processed for cell counting and biochemical analysis, while the left lung was used for histopathological examination. Accumulation of alveolar macrophages was observed in all vehicletreated groups but was minimal in the group administered saline, somewhat higher in the groups administered pure water, PBS, 0.1% Tween 20, and 1% BSA, and notably higher in the group administered 0.5% KP188. The results from BALF analysis indicated that intratracheal instillation of 0.5% KP188 also induced alveolar damage. Additionally, administering pure water did not appear to cause tissue damage. Eosinophil infiltration in the interstitial regions was histopathologically observed. Altogether, the results of this study are helpful for the selection of appropriate vehicles for use in intratracheal instillation studies.

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“…Previous studies indicated the NiO-NPs caused damage in lung and liver and induce pulmonary inflamations via reactive oxygen species (ROS) (Chang et al, 2017;Li et al, 2018;Marzban et al, 2017;Senoh et al, 2017;Shinohara et al, 2017;Yu et al, 2017;Dumala et al, 2018;Ogami et al, 2009). In vitro researches confirmed with the in vivo studies that the NiO-NPs induced an increase in ROS and caused oxidative damage in the cells (Abudayyak et al 2017a;Åkerlund et al, 2018;Di Bucchianico et al, 2018;Mohamed et al, 2018;Saquib et al, 2018).…”

Section: Tablementioning

confidence: 99%

“…Additionally, NiO-NPs are thought to be more toxic than that of fine particles because they have high solubility and release (Horie et al, 2011). Researches have mainly focused on their pulmonary toxicity, and reported that the particles induced oxidative stress and inflammatory responses in airway system (Capasso et al, 2014;Chang et al, 2017;Horie et al, 2011;Li et al, 2018;Marzban et al, 2017;Morimoto et al, 2011;Senoh et al, 2017;Yu et al, 2017). The NiO-NPs were detected in the intestinal tissue after pulmonary exposure (Shinohara et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Intestinal Epithelial Cell Toxicity Induced By Nickel Oxide Nanoparticles

Asadi¹,

Güzel²,

Özhan³

2019

tjps

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INTRODUCTION: The superior properties of nickel oxide nanoparticles (NiO-NPs) lead to wide uses in various fields; however, there has been little comprehensive knowledge about their toxicity, especially oral exposure. Because there was no study on the intestinal toxicity of NiO-NPs, the toxicity of The NiO-NPs (average size 15.0 nm) was investigated in Caco-2 (human intestinal epithelial) cells. METHODS: Following identification of their particle size distribution and cellular uptake potential, the risk of NiO-NPs' exposure have been evaluated with the crucial toxicity features including the cellular morphologic changes, the cyto-and genotoxic potentials, oxidative damage and apoptotic induction. RESULTS: According to our results, NiO-NPs caused 50% decrease in cell viability at 351.6 µg/mL, and induced DNA damage and oxidative damage at 30-150 µg/mL. It was observed that apoptosis could be the main cell death pathway at in intestinal cells exposed to NiO-NPs. DISCUSSION AND CONCLUSION: The exposure to NiO-NPs could be hazardous to the gastrointestinal system, the results should rise the concerns about using NiO-NPs in food-contacts appliance and NiO-NPs containing wastes. Further in vivo and in vitro research should be conducted to explain the specific mechanism of these particles and reduce their risk to the human.

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Comparison of single or multiple intratracheal administration for pulmonary toxic responses of nickel oxide nanoparticles in rats

Cited by 20 publications

References 19 publications

Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes

Effects of administering different vehicles via single intratracheal instillation on responses in the lung and pleural cavity of Crl:CD(SD) rats

Intestinal Epithelial Cell Toxicity Induced By Nickel Oxide Nanoparticles

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