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1.
J Toxicol Sci ; 48(7): 411-420, 2023.
Article in English | MEDLINE | ID: mdl-37394654

ABSTRACT

Multi-walled carbon nanotubes (MWCNTs), a kind of nanomaterial, are widely used in battery electrodes and composite materials, but the adverse effects associated with their accumulation in the living body have not been sufficiently investigated. MWCNTs are a fibrous material with molecules similar to asbestos fibers, and there are concerns about its effects on the respiratory system. In this study, we conducted a risk assessment by exposing mice using a previously developed nanomaterial inhalation exposure method. We quantified the exposure in the lungs by a lung burden test, evaluated the deterioration due to pneumonia using respiratory syncytial virus (RSV) infection, and measured inflammatory cytokines in bronchoalveolar lavage fluid (BALF). As a result, in the lung burden test, the amount of MWCNT in the lung increased according to the inhalation dose. In the RSV infection experiment, CCL3, CCL5, and TGF-ß, which are indicators of inflammation and lung fibrosis, were elevated in the MWCNT-exposed group. Histological examination revealed cells phagocytosing MWCNT fibers. These phagocytic cells were also seen during the recovery period from RSV infection. The present study found that MWCNT remained in the lungs for about a month or more, suggesting that the fibers may continue to exert immunological effects on the respiratory system. Furthermore, the inhalation exposure method enabled the exposure of nanomaterials to the entire lung lobe, allowing a more detailed evaluation of the effects on the respiratory system.


Subject(s)
Nanotubes, Carbon , Pneumonia , Pulmonary Fibrosis , Respiratory Syncytial Virus Infections , Mice , Animals , Nanotubes, Carbon/toxicity , Lung/pathology , Pneumonia/pathology , Bronchoalveolar Lavage Fluid , Respiratory Syncytial Viruses , Inhalation Exposure/adverse effects , Mice, Inbred C57BL
2.
Toxicol Rep ; 6: 514-520, 2019.
Article in English | MEDLINE | ID: mdl-31245279

ABSTRACT

The severity of pneumonia in respiratory syncytial virus (RSV) infection is strongly related to host immune response and external factors such as bacteria and environmental chemicals. We investigated the effect of inactivated Streptococcus pneumoniae (ISP) as non-pathogenic particles on the severity of pneumonia in RSV-infected mice. Mice were intranasally exposed to ISP before RSV infection. On day 5 post-infection, we examined tissues, virus titer, and infiltrated cells in the lungs. The ISP did not cause significant histopathological effects in the lungs of RSV infected mice, but reduced virus titer. It also reduced the ratio of lymphocyte infiltration into the lungs and consequently the ratio of macrophage increased. In addition, we found that ISP increased RANTES level in bronchoalveolar lavage fluid from RSV-infected mice on day 1 post-infection, but reduced type I interferon levels. Thus, ISP did not exacerbate pneumonia in RSV infection, rather, it might mildly reduce the severity. We characterize and discuss the inherent activity of ISP as non-pathogenic particles inducing the role of RANTES on the pneumonia in RSV infection.

3.
J Toxicol Sci ; 42(6): 789-795, 2017.
Article in English | MEDLINE | ID: mdl-29142177

ABSTRACT

To investigate the effects of perinatal exposure to tetrabromobisphenol A (TBBPA), a brominated flame retardant, on the immune system, a respiratory syncytial virus (RSV) infection mouse model was utilized. Female mice were exposed to TBBPA mixed with the diet from 10 days after conception to weaning on postnatal day 21. Offspring mice were infected intranasally with A2 strain of RSV. Although no general toxicological sign was observed, the pulmonary viral titers of offspring mice exposed to 0.1% TBBPA were significantly increased compared with the control on day 5 post-infection. TBBPA did not affect RSV growth in vitro. Histopathological analysis confirmed that the exacerbation of interstitial pneumonia was due to TBBPA- exposure in the lung tissues in RSV-infected offspring. Moreover, gene expression of interleukin (IL)-24 was shown to be elevated typically in the lung tissues of TBBPA-treated offspring by a DNA microarray and was also confirmed by immunohistopathological analysis using an anti-IL-24 antibody. Thus, developmental exposure to TBBPA affected the immune response to RSV infection, resulting in the exacerbation of pneumonia. Thus, IL-24 should be a key molecule to understand the mechanism of action of TBBPA.


Subject(s)
Disease Progression , Flame Retardants/adverse effects , Maternal Exposure/adverse effects , Pneumonia, Viral/immunology , Polybrominated Biphenyls/adverse effects , Prenatal Exposure Delayed Effects , Respiratory Syncytial Virus Infections/immunology , Animals , Cytokines/genetics , Cytokines/metabolism , Female , Gene Expression , Humans , Lung/immunology , Lung/metabolism , Male , Mice, Inbred BALB C , Pregnancy , Respiratory Syncytial Virus Infections/etiology , Tumor Cells, Cultured
4.
Environ Toxicol Pharmacol ; 39(2): 879-86, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25795424

ABSTRACT

To reveal the effects of TiO2 nanoparticles, used in cosmetics and building materials, on the immune response, a respiratory syncytial virus (RSV) infection mouse model was used. BALB/c mice were exposed once intranasally to TiO2 at 0.5mg/kg and infected intranasally with RSV five days later. The levels of IFN-γ and chemokine CCL5, representative markers of pneumonia, in the bronchoalveolar lavage fluids of RSV-infected mice had increased significantly in TiO2-exposed mice compared with the control on day 5 post-infection, but not in uninfected mice. While pulmonary viral titers were not affected by TiO2 exposure, an increase in the infiltration of lymphocytes into the alveolar septa in lung tissues was observed. Immunohistochemical analysis revealed aggregation of TiO2 nanoparticles near inflammatory cells in the severely affected region. Thus, a single exposure to TiO2 nanoparticles affected the immune system and exacerbated pneumonia in RSV-infected mice.


Subject(s)
Nanoparticles/toxicity , Pneumonia/immunology , Respiratory Syncytial Virus Infections/immunology , Titanium/toxicity , Animals , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Cell Line, Tumor , Cytokines/blood , Cytokines/immunology , Female , Humans , Lung/drug effects , Lung/immunology , Lung/virology , Mice, Inbred BALB C , Pneumonia/virology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/isolation & purification , Viral Load , Viral Proteins/analysis
5.
J Zoo Wildl Med ; 42(1): 128-30, 2011 Mar.
Article in English | MEDLINE | ID: mdl-22946383

ABSTRACT

This report describes the use of computed tomography (CT) in a nondomestic species. Postmortem CT was performed on a red kangaroo (Macropus rufus) and a diagnosis of oral osteomyelitis was made. CT examination revealed bony remodeling of the right mandible, an intraosseous lesion of the right temporal bone, muscle necrosis around the right mandible, and the absence of the right, first, upper molar tooth. Cardiac and intrahepatic gas and a distended intestine due to postmortem gas accumulation were also seen. All the lesions identified with CT were also identified by conventional necropsy, except the cardiac and intrahepatic gases. Virtopsy may be a useful procedure for the noninvasive identification of cause of death and as a guide for necropsy in animals.


Subject(s)
Macropodidae , Osteomyelitis/veterinary , Tomography, X-Ray/veterinary , Animals , Female , Osteomyelitis/pathology
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