An approach to evaluate which in vitro model and exposure method is more predictive for in vivo biological responses

The growing utilization of nanomaterials (NMs) in nanotechnology products lead to a potential increase of exposure, thus raising concerns about workers and public’s health risks. The major route of exposure is inhalation, but so far occupational and environmental atmosphere are not well characterized in terms of NMs. Despite the lack of epidemiological data on the relation between exposure to NMs and human health effects, their potential toxicity has been studied on cell cultures and animal models. Among these studies, most results are from in vitro experimentations due to the difficulty to perform in vivo studies for the enormous number of existing NMs and the necessity to reduce number of animals used in experimentations (3R rules). Nevertheless, results from animal experimentations remain the most reliable. Even if, pushed by the necessity to reduce the number of animals used in experimentation, new in vitro models and exposure methods are and have been developed, suggesting the more and more relevant alternatives to animal experimentation. Thus, many studies show that newly developed co-culture or 3D in vitro models have different nanotoxicity responses compared to classical mono-culture models. Moreover, studies using new devices allowing exposure of cells to aerosols of NMs show different nanotoxicity responses compared to exposure to suspensions of NMs. However, which of these models and exposure methods is more predictive for in vivo responses is yet to be defined. In order to better define which in vitro model and which exposure method is more predictive for in vivo pulmonary nanotoxicity data, three different methodologies will be implemented

Idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) and sleep disruption : Melatonin Assessment in saliva and urine

International audienceSleep disruption is frequently reported by people with idiopathic environmental intolerance attributed to electromagnetic fields or IEI-EMF. The physiopathology of this association is not clear. We aimed to evaluate whether melatonin level was affected in IEI-EMFs patients. Melatonin levels in saliva and urine were quantified by immunoassay techniques in a session without intentional exposure to EMF. Sleep quality was assessed by questionnaires.Significant differences in PSQI and ESS scores between compared groups were observed. Likewise, a higher proportion of pathological sleep for ESS was found in IEI-EMF group. Results indicate that melatonin is not associated with different sleep troubles reported by IEI-MFs patients

Inflammation system and immunological characterization of patients suffering from electrohypersensitivity

International audienceElectrohypersensitivity (EHS) is characterized by a variety of atypical symptoms attributed to EMF exposure. Diagnostic markers are lacking and research of these biomarkers could greatly help understanding this syndrome. The present study aimed to look to the pattern of some selected biological markers of immunological system in EHS individuals. In this regard, we compared levels of immunoglobulin A, neopterin and C Reactive Protein between patient with EHS and their matched control group. In our study, we failed to show a strong marker from immunological system despite a difference in participants according to the EHS duration for neopterin (difference between subgroups between short-term and long term affected participants)

Disturbed sleep in individuals with idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) : Melatonin assessment as a biological marker

Individuals who suffer from idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) complain of a variety of adverse health effects. Troubled sleep remains a recurrent and common symptom in IEI-EMF individuals. Melatonin, a circadian hormone, plays a major role in the sleep process. In this study, we compared levels of melatonin between a sensitive group (IEI-EMF, n=30) and a non-sensitive control group (non IEI-EMF, n=25) without exposure to electromagnetic sources. Three questionnaires were used to evaluate the subjective quality and sleep quantity: the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index and the Spiegel Sleep Inventory. Melatonin was quantified in saliva and its major metabolite 6-sulfatoxymelatonin (aMT6s) in urine. Melatonin levels were compared by a two-way analysis of variance at various times between the control and IEI-EMF group. Despite significantly different sleep scores between the two groups, with a lower score in the IEI-EMF group (P0.05) and urine aMT6s (P>0.05)

Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro

International audienceThe health risks of nanoparticles remain a serious concern given their prevalence from industrial and domestic use. The primary route of titanium dioxide nanoparticle exposure is inhalation. The extent to which nanoparticles contribute to cellular toxicity is known to associate induction of oxidative stress. To investigate this problem further, the effect of titanium dioxide nanoparticles was examined on cell lines representative of alveolo-capillary barrier. The present study showed that all nanoparticle-exposed cell lines displayed ROS generation. Macrophage-like THP-1 and HPMEC-ST1.6R microvascular cells were sensitive to endogenous redox changes and underwent apoptosis, but not alveolar epithelial A549 cells. Genotoxic potential of titanium dioxide nanoparticles was investigated using the activation of γH2AX, activation of DNA repair proteins and cell cycle arrest. In the sensitive cell lines, DNA damage was persistent and activation of DNA repair pathways was observed. Moreover, western blot analysis showed that specific pathways associated with cellular stress response were activated concomitantly with DNA repair or apoptosis. Nanoparticles-induced oxidative stress is finally signal transducer for further physiological effects including genotoxicity and cytotoxicity. Within activated pathways, HSP27 and SAPK/JNK proteins appeared as potential biomarkers of intracellular stress and of sensitivity to endogenous redox changes, respectively, enabling to predict cell behavior