Project description:This study investigates transcriptomic differences in the lung and liver after pulmonary exposure to two Graphene based materials with similar physical properties, but different surface chemistry. Female C57BL/6 mouse were exposed by a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of graphene oxide (GO) or reduced graphene oxide (rGO). Pulmonary and hepatic transcriptional changes were compared to identify commonly and uniquely perturbed functions and pathways by GO and rGO. These changes were then related to previously analyzed endpoints. GO exposure induced more differentially expressed genes, affected more functions, and perturbed more pathways compared to rGO, both in the lung and liver.
Project description:Multi-walled carbon nanotubes (MWCNTs) are among the most promising nanomaterials because of their physical and chemical properties. However, since they are biopersistent fiber-like materials which share similarities with asbestos, concerns have arisen about their health effects. With their various industrial usages, occupational exposure to MWCNTs may occur mainly by inhalation as these nanomaterials can get aerosolised. The number of toxicological studies on CNTs has steadily increased for the last decades. Different works showed that MWCNT exposure by inhalation or intratracheal instillation could lead to pulmonary toxicity, such as lung inflammation, genotoxicity, fibrosis or lung cancer (Kasai et al. 2015, Kasai et al. 2016, Porter et al. 2013, Suzui et al. 2016). To date, only one MWCNT (MWNT-7) has been classified as possibly carcinogen to human (Group 2B) while the others have not been as classifiable as to their carcinogenicity to humans (Group 3) because of the lack of data on their carcinogenic potential (IARC 2017). Because of the wide variety of CNTs with various length, diameter or functionalisation, additional effort is required to assess their pulmonary toxicity. As a complementary approach to conventional toxicological assays, the omics methods are useful technologies for the mechanistic understanding of the toxicological effects observed following exposure to chemicals and particulate matters. Importantly, they can also be used as predictive tools for identifying the mode of action of other particles with similar physical and chemical characteristics. These molecular approaches may also be used for the discovery of exposure markers or early markers of adverse effects, before the appearance of clinical signs of a disease (Rahman et al. 2017). Several studies assessed gene expression alteration following in vivo exposure to CNTs (Poulsen et al. 2015, Snyder-Talkington et al. 2013, Ellinger-Ziegelbauer and Pauluhn 2009). These omics approaches were used to identify genes and pathways modulated in response to exposure. However, there are still too few studies to assess the link between MWCNT physico-chemical properties, global gene or protein expression profiles, and long-term effects. In a previous study, we showed that inhalation of two pristine MWCNTs, the long and thick NM-401, and the short and thin NM-403, induced alveolar neutrophilic granulocyte influx, a hallmark of inflammation, which was proportional to the lung CNT BET surface deposited dose (Gate et al. 2019). However, due to their different physical and chemical properties, one could assume that these two CNTs may have diverse toxicological profiles, but the conventional toxicology approaches used in this early work were probably not sensitive enough to identify such differences. In order to gain additional insight about their toxicological properties, in the current study, we compare the alteration induced by the two MWCNTs on the transcriptome in the lung tissue and the proteome in the broncho-alveolar lavage fluid (BALF) after rat exposure by inhalation. The omics analyses were performed from 3 days up to 180 days.
Project description:Multi-walled carbon nanotubes (MWCNTs) are among the most promising nanomaterials because of their physical and chemical properties. However, since they are biopersistent fiber-like materials which share similarities with asbestos, concerns have arisen about their health effects. With their various industrial usages, occupational exposure to MWCNTs may occur mainly by inhalation as these nanomaterials can get aerosolised. The number of toxicological studies on CNTs has steadily increased for the last decades. Different works showed that MWCNT exposure by inhalation or intratracheal instillation could lead to pulmonary toxicity, such as lung inflammation, genotoxicity, fibrosis or lung cancer (Kasai et al. 2015, Kasai et al. 2016, Porter et al. 2013, Suzui et al. 2016). To date, only one MWCNT (MWNT-7) has been classified as possibly carcinogen to human (Group 2B) while the others have not been as classifiable as to their carcinogenicity to humans (Group 3) because of the lack of data on their carcinogenic potential (IARC 2017). Because of the wide variety of CNTs with various length, diameter or functionalisation, additional effort is required to assess their pulmonary toxicity. As a complementary approach to conventional toxicological assays, the omics methods are useful technologies for the mechanistic understanding of the toxicological effects observed following exposure to chemicals and particulate matters. Importantly, they can also be used as predictive tools for identifying the mode of action of other particles with similar physical and chemical characteristics. These molecular approaches may also be used for the discovery of exposure markers or early markers of adverse effects, before the appearance of clinical signs of a disease (Rahman et al. 2017). Several studies assessed gene expression alteration following in vivo exposure to CNTs (Poulsen et al. 2015, Snyder-Talkington et al. 2013, Ellinger-Ziegelbauer and Pauluhn 2009). These omics approaches were used to identify genes and pathways modulated in response to exposure. However, there are still too few studies to assess the link between MWCNT physico-chemical properties, global gene or protein expression profiles, and long-term effects. In a previous study, we showed that inhalation of two pristine MWCNTs, the long and thick NM-401, and the short and thin NM-403, induced alveolar neutrophilic granulocyte influx, a hallmark of inflammation, which was proportional to the lung CNT BET surface deposited dose (Gate et al. 2019). However, due to their different physical and chemical properties, one could assume that these two CNTs may have diverse toxicological profiles, but the conventional toxicology approaches used in this early work were probably not sensitive enough to identify such differences. In order to gain additional insight about their toxicological properties, in the current study, we compare the alteration induced by the two MWCNTs on the transcriptome in the lung tissue and the proteome in the broncho-alveolar lavage fluid (BALF) after rat exposure by inhalation. The omics analyses were performed from 3 days up to 180 days.
Project description:Carbon nanotubes (CNTs) are newly developed nanomaterials with unique chemical and physical properties. Exposure to airborne CNTs in occupational settings or via consumer products is expected to increase significantly within the next decade due to the vigorous synthesis and applications of these materials in numerous consumer and industrial activities. Previous studies have shown that multiwalled CNT (MWCNT) induce pulmonary inflammation and pulmonary fibrosis. In the present study, we investigated genotoxic potential of MWCNTs. Female MutaMouse were exposed to 42.7 ug/mouse or 128 ug/mouse doses of MWCNTs Mitsui XNRi-7 or NM 401 once a week for four consecutive weeks. Doses were administered via intratracheal instillation. Lung tissues were collected 56 days post-exposure. Bronchoalveolar lavage(BAL) fluid cellularity, BAL and lung tissue DNA damage (COMET assay), lacz mutation frequency and global gene expression changes in lung tissue were determined.
Project description:Physical exercise is a cornerstone for preventing diet-induced obesity, while it is unclear whether physical exercise could offset high-fat, high-calories diet (HFCD)-induced cardiac dysfunction. Here, mice were fed with HFCD and simultaneously subjected to physical exercise. As expected, physical exercise prevented HFCD-induced whole-body fat deposition. However, physical exercise exacerbated HFCD-induced cardiac damage. Further metabolomic analysis results showed that physical exercise induced circulating lipid redistribution, leading to excessive cardiac lipid uptake and lipotoxicity. Our study provides valuable insights into the cardiac effects of exercise in mice fed with HFCD, suggesting that counteracting the negative effect of HFCD by simultaneous physical exercise might be detrimental. Moreover, inappropriate physical exercise may damage certain organs even though it leads to weight loss and overall metabolic benefits. Of note, the current findings are based on animal experiments, the generalizability of these findings beyond this specific diet and mouse strain remains to be further explored.
Project description:Activation of the innate immune system via pattern recognition receptors (PRRs) is key to generate lasting adaptive immunity. PRRs detect unique chemical patterns associated with invading microorganism, but if and how the physical properties of PRR ligands influence development of the immune response remains unknown. Through the study of fungal mannans we show that the physical form of PRR ligands dictates the immune response. Soluble mannans are immunosilent in the periphery but elicit a potent pro-inflammatory response in the draining lymph node (dLN). By modulating the physical form of mannans, we developed a formulation that targets both the periphery and dLN. When combined with viral glycoprotein antigens, this mannan formulation broadens epitope recognition, elicits potent antigen-specific neutralizing antibodies, and confers protection against viral infections of the lung. Thus, the physical properties of microbial ligands determine the outcome of the immune response and can be harnessed for vaccine development.