Biodistribution and clearance of instilled carbon nanotubes in rat lung

<p>Abstract</p> <p>Background</p> <p>Constituted only by carbon atoms, CNT are hydrophobic and hardly detectable in biological tissues. These properties make biokinetics and toxicology studies more complex.</p> <p>Methods</p> <p>We propose here a method to investigate the biopersistence of CNT in organism, based on detection of nickel, a metal present in the MWCNT we investigated.</p> <p>Results and conclusion</p> <p>Our results in rats that received MWCNT by intratracheal instillation, reveal that MWCNT can be eliminated and do not significantly cross the pulmonary barrier but are still present in lungs 6 months after a unique instillation. MWCNT structure was also showed to be chemically modified and cleaved in the lung. These results provide the first data of CNT biopersistence and clearance at 6 months after respiratory administration.</p

Characterization of a new coculture model of alveolo-capillary barrier developed to study the translocation and the toxicity of nanoparticles

One of the vital barriers in the human body is the air-blood barrier (ABB) in the lung. With an area of approximately 140 m2 the alveoli are functionally the most important element of the lung. Therefore, we developed an in vitro model that mimics the ABB in order to assess the translocation and the toxicity of nanoparticles (NP). In order to better mimic the reality, the model is composed of 3 cell types: THP-1 differentiated-macrophages and epithelial cells (A549 or NCI-H441) cultivated on the apical membrane of an insert, and HUVEC-CS endothelial cells on the basal side. Contrary to A549 cell line, NCI-H441 cells are not type II pneumocytes, but we showed that they are able to establish reliable junctional complexes. Consequently, they are good candidates to build a model of ABB. Coculture with THP-1 macrophages revealed to be essential to assess inflammatory process close to reality because 20 nm SiO2 and TiO2 NP-exposed macrophage's conditioned medium does not trigger the same inflammatory response compared to direct treatment of epithelial cells by NP. On the other hand, coculture of NCI-H441 cells with HUVEC-CS cells was tested with different coatings (collagen, elastin, fibronectin) to determine the best conditions in terms of cell differentiation. Moreover, different insert pore-sizes were tested (0.4 um; 1 um and 3 um) and optimal sizes (0.4 um and 1 um) were chosen according to NP translocation and cell growth. Therefore, the first results with our complete model underline the importance of using macrophages to assess inflammatory and translocation process on the ABB

Effect of sub-chronic GSM exposure on glia

Low power electromagnetic elds (EMF) are suspected to produce biological e ects in the nervous system. The study of AL Mausset et al. (December 2004) showed an increase of a speci c marker of glial cells, the GFAP (Glial Fibrillary Acidic Protein), in striatum, hippocampus and cortex, 72 hours after a 15 min exposure to GSM-type radiation at a local SAR of 6 W/kg (head). This study is con rmed by Brillaud et al (2007

Neurobiological effects of repeated radiofrequency exposures in male senescent rats

The increasing use of mobile phones by aging people raises issues about the effects of radiofrequency electromagnetic fields (RF-EMF) on the aging central nervous system. Here, we tested if mobile phone RF-EMF exposures could exacerbate senescence-typical neurobiological deficits. Thus, aged (22–24 months) and young (4–6 months) adult male rats were subjected to head RF-EMF exposures (900 MHz, specific absorption rate (SAR) of 6 W/kg, 45 min/day for 1 month in restraint rockets). To assess senescence-typical neurobiological deficits, spatial memory, emotional memory, anxiety-related behavior, locomotor activity, interleukins (IL)-1β and 6, glial fibrillary acidic protein and corticosterone were measured. Aged rats presented deficits in spatial learning, exploration, anxiety-related behaviors, and increased hippocampal ILs and cortical IL-1β. Results showed that senescence-typical neurobiological deficits were not modified by RF-EMF exposures. RF-EMF-exposed rats (young and aged adults pooled) had decreased anxiety-related behaviors in the elevated plus maze. This study which is the first to assess RF-EMF exposures during late aging did not support the hypothesis of a specific cerebral vulnerability to RF-EMF during senescence. More investigations using longer RF-EMF exposures should be performed to conclude regarding the inoffensiveness of RF-EMF exposures

Impact of Cerebral Radiofrequency Exposures on Oxidative Stress and Corticosterone in a Rat Model of Alzheimer's Disease

Background: Alzheimer's disease (AD) is the most common type of neurodegenerative disease leading to dementia. Several studies suggested that mobile phone radiofrequency electromagnetic field (RF-EMF) exposures modified AD memory deficits in rodent models. Objective: Here we aimed to test the hypothesis that RF-EMF exposure may modify memory through corticosterone and oxidative stress in the Samaritan rat model of AD. Methods: Long-Evans male rats received intracerebroventricular infusion with ferrous sulphate, amyloid-beta 1-42 peptide, and buthionine-sufloximine (AD rats) or with vehicle (control rats). To mimic cell phone use, RF-EMF were exposed to the head for 1 month (5 days/week, in restraint). To look for hazard thresholds, high brain averaged specific absorption rates (BASAR) were tested: 1.5 W/Kg (15 min), 6 W/Kg (15 min), and 6 W/Kg (45 min). The sham group was in restraint for 45 min. Endpoints were spatial memory in the radial maze, plasmatic corticosterone, heme oxygenase-1 (HOl), and amyloid plaques. Results: Results indicated similar corticosterone levels but impaired memory performances and increased cerebral staining of thioflavine and of HOl in the sham AD rats compared to the controls. A correlative increase of cortical HOl staining was the only effect of RF-EMF in control rats. In AD rats, RF-EMF exposures induced a correlative increase of hippocampal HO1 staining and reduced corticosterone. Discussion: According to our data, neither AD nor control rats showed modified memory after RF-EMF exposures. Unlike control rats, AD rats showed higher hippocampal oxidative stress and reduced corticosterone with the higher BASAR. This data suggests more fragility related to neurodegenerative disease toward RF-EMF exposures

Assessment of an in vitro model of pulmonary barrier to study the translocation of nanoparticles

International audienceAs the lung is one of the main routes of exposure to manufactured nanoparticles, we developed an in vitro model resembling the alveolo-capillary barrier for the study of nanoparticle translocation. In order to provide a relevant and ethical in vitro model, cost effective and easy-to-implement human cell lines were used. Pulmonary epithelial cells (Calu-3 cell line) and macrophages (THP-1 differentiated cells) were cultivated on the apical side and pulmonary endothelial cells (HPMEC-ST1.6R cell line) on the basal side of a microporous polyester membrane (Transwell). Translocation of non-functionalized (51 and 110 nm) and aminated (52 nm) fluorescent polystyrene (PS) nanobeads was studied in this system. The use of Calu-3 cells allowed high transepithelial electrical resistance (TEER) values (>1000 O cm2) in co-cultures with or without macrophages. After 24 h of exposure to non-cytotoxic concentrations of non-functionalized PS nanobeads, the relative TEER values (%/t0) were significantly decreased in co-cultures. Epithelial cells and macrophages were able to internalize PS nanobeads. Regarding translocation, Transwell membranes per se limit the passage of nanoparticles between apical and basal side. However, small non-functionalized PS nanobeads (51 nm) were able to translocate as they were detected in the basal side of co-cultures. Altogether, these results show that this co-culture model present good barrier properties allowing the study of nanoparticle translocation but research effort need to be done to improve the neutrality of the porous membrane delimitating apical and basal sides of the model

Alteration of adaptive behaviors of progeny after maternal mobile phone exposure

International audienceExposure of pregnant women to radiofrequency (RF) devices raises questions on their possible health consequences for their progeny. We examined the hazard threshold of gestational RF on the progeny's glial homeostasis, sensory-motor gating, emotionality, and novelty seeking and tested whether maternal immune activation would increase RF toxicity. Pregnant dams were daily restrained with loop antennas adjoining the abdomen (fetus body specific absorption rates (SAR): 0, 0.7, or 2.6 W/kg) and received three lipopolysaccharide (LPS) intra-peritoneal injections (0 or 80 mu g/kg). Scores in the prepulse startle inhibition, fear conditioning, open field, and elevated plus maze were assessed at adolescence and adulthood. Glial fibrillary acidic protein (GFAP) and interleukines-1 beta (ILs) were quantified. LPS induced a SAR-dependent reduction of the prepulse startle inhibition in adults. Activity in the open field was reduced at 2.6 W/kg at adolescence. GFAP and ILs, emotional memory, and anxiety-related behaviors were not modified. These data support the hypothesis that maternal immune activation increased the developmental RF exposure-induced long-term neurobiological impairments. These data support the fact that fetuses who receive combined environmental exposures with RF need special attention for protection

GFAP expression in the rat brain following sub-chronic exposure to a 900 MHz electromagnetic field signal

International audienceMethods: Sprague-Dawley rats were exposed for 45 min/day at a brain-averaged specific absorption rate (SAR) = 1.5 W/kg or 15 min/day at a SAR = 6 W/kg for five days per week during an eight-week period. GFAP expression was measured by the immunocytochemistry method in the following rat brain areas: Prefrontal cortex, cerebellar cortex, dentate gyrus of the hippocampus, lateral globus pallidus of the striatum, and the caudate putamen. Results: Compared to the sham-treated rats, those exposed to the sub-chronic GSM (Global System for mobile communications) signal at 1.5 or 6 W/kg showed an increase in GFAP levels in the different brain areas, three and ten days after treatment. Conclusion: Our results show that sub-chronic exposures to a 900 MHz EMF signal for two months could adversely affect rat brain (sign of a potential gliosis)