Search

Carbon nanotubes (CNTs) are speculated to cause mesothelioma by persistent inflammation, oxidative stress, tissue injury, and genotoxicity. To investigate the pleural response to CNTs, we exposed C57BL/6 mice by intrapleural injection of 0.2 or 5 µg multiwalled CNTs (MWCNT-7, NM-401, and NM-403) or single-walled CNTs (NM-411). Inflammatory response, cellular reactive oxygen species (ROS) production of pleural lavage cells, and genotoxicity in cells from the mesothelial surface were assessed at days 1 and 90 after the exposure. Long and rigid types of MWCNTs (MWCNT-7 and NM-401) caused acute inflammation, characterized by influx of macrophages, neutrophils, and eosinophils into the pleural cavity. The inflammation was still evident at 90 days after the exposure, although it had reduced dramatically. The cellular ROS production was increased at day 90 after the exposure to MWCNT-7 and NM-401. The short and tangled type of MWCNT (ie NM-403) did not cause pleural inflammation or ROS production in pleural fluid cells. The exposure to NM-411 did not cause consistent inflammation responses or cellular ROS production. Levels of DNA strand breaks and DNA oxidation damage were unaltered, except for NM-411-exposed mice that had increased levels of DNA strand breaks at 90 days after the exposure. In conclusion, the long and rigid CNTs caused prolonged inflammatory response and increased ROS production in pleural lavage cells, yet it was not reflected in higher levels of DNA damage in pleural tissue. [ABSTRACT FROM AUTHOR]

Ambient air pollution including ozone and especially particulate matter represents important causes of cardiovascular disease. However, there is limited knowledge on indoor air dust with respect to this risk and the potential interactions between dust and ozone. Here, we exposed 23 healthy elderly subjects for 5.5 h, to either clean air, house dust at 275 µg/m³ (diameter < 2.5 µm), ozone at 100 ppb or combined house dust and ozone in a double-blinded randomized cross-over study. The combined house dust and ozone exposure was associated with a 48% (95% CI 24%-65%) decrease as compared with the clean air exposure, in CD34+KDR+ late endothelial progenitor cells (EPCs) per leukocyte in the blood shortly after exposure, whereas none of the single exposures resulted in a significant effect. The combined exposure also increased reactive oxygen species production capacity in granulocytes and monocytes as well as an up-regulation of interleukin-8 mRNA levels in leukocytes. Ozone alone reduced the gene expression of tumor necrosis factor and C-C motif chemokine ligand 2, while dust alone showed no effects. The combined exposure to house dust and ozone also reduced levels of oxidized purines in DNA consistent with concomitant up-regulation of mRNA of the repair enzyme 8-oxoguanine DNA glycosylase. The reduction in late EPCs can be an indicator of cardiovascular risk caused by the combination of pulmonary oxidative stress induced by ozone and the inflammatory potential of the house dust. These data were corroborated with in vitro findings from exposed human macrophages and endothelial cells. [ABSTRACT FROM AUTHOR]

This study investigated a number of biomarkers, associated with systemic inflammation as well as genotoxicity, in 53 young and healthy subjects participating in a course to become firefighters, while wearing personal protective equipment (PPE). The exposure period consisted of a 3-day training course where the subjects participated in various live-fire training exercises. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The personal exposure was measured as dermal polycyclic aromatic hydrocarbon (PAH) concentrations and urinary excretion of 1-hydroxypyrene (1-OHP). The subjects were primarily exposed to particulate matter (PM) in by-stander positions, since the self-contained breathing apparatus effectively prevented pulmonary exposure. There was increased dermal exposure to pyrene (68.1%, 95% CI: 52.5%, 83.8%) and sum of 16 polycyclic aromatic hydrocarbons (ΣPAH; 79.5%, 95% CI: 52.5%, 106.6%), and increased urinary excretion of 1-OHP (70.4%, 95% CI: 52.5%; 106.6%) after the firefighting exercise compared with the mean of two control measurements performed 2 weeks before and 2 weeks after the firefighting course, respectively. The level of Fpg-sensitive sites in peripheral blood mononuclear cells (PBMCs) was increased by 8.0% (95% CI: 0.02%, 15.9%) compared with control measurements. The level of DNA strand breaks was positively associated with dermal exposure to pyrene and ΣPAHs and urinary excretion of 1-OHP. Fpg-sensitive sites were only associated positively with PAHs. Biomarkers of inflammation and lung function showed no consistent response. In summary, the study demonstrated that PAH exposure during firefighting activity was associated with genotoxicity in PBMCs. [ABSTRACT FROM AUTHOR]

Silver (Ag) nanoparticles (NPs) are currently among one of the most widely used nanomaterials. This in turn, implies an increased risk of human and environmental exposure. Alcohol abuse is a global issue with millions of people in the general population affected by the associated adverse effects. The excessive consumption of alcohol is a prominent cause of chronic liver disease which manifest in multiple disorders. In this study, the adverse health effects of Ag NP exposure were investigated in models of alcoholic hepatic disease in vitro and in vivo. The data showed that Ag NP induced hepatic health effects were aggravated in the alcohol pretreated mice in comparison to controls with regards to an organ specific inflammatory response, changes in blood biochemistry, acute phase response and hepatic pathology. In addition, alcoholic disease influenced the organ's ability for recovery post-NP challenge. Additionally, it is demonstrated that the in vivo data correlated well with in vitro findings where ethanol pretreatment of hepatocytes resulted in significantly increased inflammatory response post-Ag NP exposure. To the best of our knowledge this is the first study of its kind to investigate nano-sized material-induced hepatic pathology in models representative of susceptible individuals (those with pre-existing alcohol liver disease) within the population. This is an area of research in the field of nanotoxicology, and in particular with regard to NP risk assessment that is almost entirely overlooked. [ABSTRACT FROM AUTHOR]

Accumulating evidences indicate that pulmonary exposure to carbon nanotubes (CNTs) is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of 2 types of multiwalled CNTs (MWCNTs) in apolipoprotein E−/− mice, wild-type mice, and cultured cells. The ApoE−/− mice had accelerated plaque progression in aorta after 5 intracheal instillations of MWCNT (25.6 μg/mouse weekly for 5 weeks). The exposure was associated with pulmonary inflammation, lipid peroxidation, and increased expression of inflammatory, oxidative stress, DNA repair, and vascular activation response genes. The level of oxidatively damaged DNA in lung tissue was unaltered, probably due to increased DNA repair capacities. Despite upregulation of inflammatory genes in the liver, effects on systemic cytokines and lipid peroxidation were minimal. The exposure to MWCNTs in cultured human endothelial cells increased the expression of cell adhesion molecules (ICAM1 and VCAM1). In cocultures, there was increased adhesion of monocytes to endothelial cells after exposure to MWCNT. The exposure to both types of MWCNT was also associated with increased lipid accumulation in monocytic-derived foam cells, which was dependent on concomitant oxidative stress because the antioxidant N-acetylcysteine inhibited the lipid accumulation. Collectively, our results indicate that exposure to MWCNT is associated with accelerated progression of atherosclerosis, which could be related to both increased adherence of monocytes onto the endothelium and oxidative stress-mediated transformation of monocytes to foam cells. [ABSTRACT FROM PUBLISHER]

Wood combustion is a significant source of ambient particulate matter (PM) in many regions of the world. Exposure occurs through inhalation or ingestion after deposition of wood smoke particulate matter (WSPM) on crops and food. We investigated effects of ambient PM and WSPM by intragastric or intratracheal exposure in terms of oxidative stress, inflammation, genotoxicity, and DNA repair after 24 h in liver and lung tissue of rats. Rats were exposed to WSPM from high or low oxygen combustion and ambient PM collected in areas with and without many operating wood stoves or carbon black (CB) at the dose of 0.64 mg/kg body weight. The levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine, 1,N6-etheno-2′-deoxyadenosine, and 1-N2-etheno-2′-deoxyguanosine (ɛdG) were significantly increased with 23% (95% confidence interval [CI]: 0.1–45%), 54% (95% CI:18–90%), and 73% (95% CI: 31–134%) in the liver of rats exposed orally to CB, respectively. Rats orally exposed to PM from the wood stove area and low oxygen combustion WSPM (LOWS) had 35% (95% CI: 0.1–71%) and 45% (95% CI: 10–82%) increased levels of ɛdG in the liver, respectively. No significant differences were observed for bulky DNA adducts. Increased gene expression of proinflammatory cytokines, heme oxygenase-1, and oxoguanine DNA glycosylase 1 was observed in the liver following intragastric exposure and in the lung following instillation in particular of LOWS. Exposure to LOWS also increased the proportion of neutrophils in BAL fluid. These results indicate that WSPM and CB exert the strongest effect in terms of oxidative stress–induced response, inflammation, and genotoxicity in the organ closest to the port of entry. [ABSTRACT FROM AUTHOR]