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

Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure

International audienceExperiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems. (C) 2010 Elsevier B.V. All rights reserved

Biodistribution and Clearance of TiO2 Nanoparticles in Rats after Intravenous Injection.

Titanium dioxide (TiO2) nanoparticles are used in many applications. Due to their small size, easy body penetration and toxicological adverse effects have been suspected. Numerous studies have tried to characterize TiO2 translocation after oral, dermal or respiratory exposure. In this study, we focused on TiO2 nanoparticle biodistribution, clearance and toxicological effects after intravenous injection, considering TiO2 translocation in the blood occurs. Using ICP-OES, transmission electron microscopy, and histological methods, we found TiO2 accumulation in liver, lungs and spleen. We estimated TiO2 nanoparticles' half life in the body to about 10 days. Clinical biomarkers were also quantified for 56 days to identify potential toxicological impact on lungs, blood, liver, spleen and kidneys. Results showed absence of toxicological effects after TiO2 intravenous injection at concentrations of 7.7 to 9.4 mg/kg

Tritiated Water Exposure in Zebrafish (Danio rerio): Effects on the Early‐Life Stages

International audienceTritium, a radioactive isotope of hydrogen of natural and anthropogenic origin, is ubiquitously present in theenvironment. Effluents of nuclear centers of production are significant anthropogenic sources. With the upcoming project of thermonuclear fusion, tritium releases in the environment may increase. It is therefore important to characterize the ecologicalrisk linked to tritium. The effects of tritiated water (HTO) were therefore studied in zebrafish larvae exposed for 10 d todifferent dose rates, 1.1 × 102, 4.1 × 102, and 3.8 × 103 μGy/h for larvae corresponding, respectively, to a water contaminationof 104, 105, and 106 Bq/mL of HTO. Those dose rates were higher than 10 μGy/h, which is the threshold recommended tostart monitoring ecosystems where radiological contaminants are present. Mortality, embryo‐larval development, immune toxicity, genotoxicity, neurotoxicity, and alterations of tissues were investigated. The results showed that HTO exposure induced DNA damage and reactive oxygen species production and modulated the expression of genes involved in detoxificationprocesses. Moreover, modifications of the muscular tissues (degradation of myofibrils at 4 d post fertilization anddisorganization of mitochondria at later stages) were observed. The results differed with HTO dose rates and with developmentalstages. These results will drive future research for the development of new HTO‐sensitive biomarkers and willallow us to progress in the characterization of the modes of action of tritium in fish

Effects of gamma ionizing radiation exposure on Danio rerio embryo-larval stages - comparison with tritium exposure

International audienceThe objective was to investigate the effects of ionizing radiation induced in zebrafish early life stages by coupling responses obtained at the molecular (genotoxicity, ROS production, gene expression) and phenotypic (tissue alteration, embryo-larval development) levels. Here we present results obtained after exposure of 3 hpf larvae to 10 days of gamma irradiation at 3.3x101, 1.3x102 and 1.2x103 µGy/h. Dose rates used in these studies were chosen to be in the ‘derived consideration reference level’ (DCRL) for gamma irradiation where deleterious effects can appear in freshwater fish. Also, these dose rates were similar to the ones already tested on tritium (beta ionizing radiation) in our previous work, in order to compare both types of ionizing radiation. Results showed that gamma irradiation did not induce any effect on survival and hatching. No effect was observed on DNA damages, but ROS production was increased. Muscle damages were observed for all tested dose rates, similarly to previous results obtained with tritium (beta ionizing radiation) at similar dose rates. Some molecular responses therefore appeared to be relevant for the study of gamma ionizing radiation effects in zebrafish

Effects of depleted uranium on the reproductive success and F1 generation survival of zebrafish (Danio rerio)

Despite the well-characterized occurrence of uranium (U) in the aquatic environment, very little is known about the chronic exposure of fish to low levels of U and its potential effect on reproduction. Therefore, this study was undertaken to investigate the effects of environmental concentrations of depleted U on the reproductive output of zebrafish (Danio rerio) and on survival and development of the F1 embryo-larvae following parental exposure to U. For that purpose, sexually mature male and female zebrafish were exposed to 20 and 250 µg/L of U for 14 days and allowed to reproduce in clean water during a further 14-day period. At all sampling times, whole-body vitellogenin concentrations and gonad histology were analyzed to investigate the effects of U exposure on these reproductive endpoints. In addition, accumulation of U in the gonads and its genotoxic effect on male and female gonad cells were quantified. The results showed that U strongly affected the capability of fish to reproduce and to generate viable individuals as evidenced by the inhibition of egg production and the increased rate of mortality of the F1 embryos. Interestingly, U exposure resulted in decreased circulating concentrations of vitellogenin in females. Increased concentrations of U were observed in gonads and eggs, which were most likely responsible for the genotoxic effects seen in fish gonads and in embryos exposed maternally to U. Altogether, these findings highlight the negative effect of environmentally relevant concentrations of U which alter the reproductive capability of fish and impair the genetic integrity of F1 embryos raising further concern regarding its effect at the population level

Use of combined microscopic and spectroscopic techniques to reveal interactions between uranium and Microbacterium sp. A9, a strain isolated from the Chernobyl exclusion zone

Although uranium (U) is naturally found in the environment, soil remediation programs will become increasingly important in light of certain human activities. This work aimed to identify U(VI) detoxification mechanisms employed by a bacteria strain isolated from a Chernobyl soil sample, and to distinguish its active from passive mechanisms of interaction. The ability of the Microbacterium sp. A9 strain to remove U(VI) from aqueous solutions at 4 °C and 25 °C was evaluated, as well as its survival capacity upon U(VI) exposure. The subcellular localisation of U was determined by TEM/EDX microscopy, while functional groups involved in the interaction with U were further evaluated by FTIR; finally, the speciation of U was analysed by TRLFS. We have revealed, for the first time, an active mechanism promoting metal efflux from the cells, during the early steps following U(VI) exposure at 25 °C. The Microbacterium sp. A9 strain also stores U intracellularly, as needle-like structures that have been identified as an autunite group mineral. Taken together, our results demonstrate that this strain exhibits a high U(VI) tolerance based on multiple detoxification mechanisms. These findings support the potential role of the genus Microbacterium in the remediation of aqueous environments contaminated with U(VI) under aerobic conditions

Effets du tritium in vivo et in situ sur la santé des poissons : approche multi biomarqueurs et liens entre les échelles biologiques

International audienceLe contexte des effets biologiques de l’exposition aux rayonnements ionisants est une préoccupation majeure pour la radioprotection de l’homme et de l’environnement. Ceci a récemment été mis en exergue après l’accident de Fukushima, notamment dans le contexte de la quantification du risque pour la santé des individus et populations exposées aux faibles doses. Augmenter la connaissance des effets des faibles doses sur les espèces humaines et non-humaines permettrait de gagner en précision pour la prédiction des effets et la prise de décision.L’industrie nucléaire rejette dans l’environnement différents types de radionucléides, principalement des émetteurs gamma (137Cs, 60Co, 54Mn), mais aussi du tritium, le plus important en termes de production (200g correspondant à 7,2.106 Bq/an dans le monde). Le tritium est un isotope radioactif de l’hydrogène qui émet des rayonnements beta. Sa demi-vie est de 12,3 ans. Les rejets de tritium sont supposés augmenter dans le futur avec le développement de réacteurs basés sur la fusion nucléaire (ITER). Les écosystèmes aquatiques, habités pas de nombreuses espèces animales et végétales, représentent généralement le récepteur final d’un grand nombre de polluants, incluant des radionucléides dont le tritium. L’exposition à des niveaux élevés de radionculéides est connue pour induire de nombreuses altérations sur différentes fonctions de l’organisme, de la molécule (intégrité de l’ADN) à la population (effets sur la survie et la reproduction). Cependant, les effets de faibles niveaux d’exposition, plus pertinents d’un point de vue environnemental, sont peu connus.Cette présentation résume les différents travaux menés depuis plusieurs années à l’IRSN sur le tritium, sur différents modèles biologiques : le poisson zèbre, Danio rerio, espèce modèle facile à maintenir en laboratoire, afin de comprendre les mécanismes d’action du tritium dans le cadre d’expositions contrôlées ; et le tête de boule, Pimephales promelas, espèce autochtone du continent Nord-Américain, afin d’étudier les effets du tritium seul ou un mélange dans un contexte réel de contamination aux effluents d’un centre de recherche. L’évaluation des effets du tritium a été réalisée par l’analyse d’une batterie de biomarqueurs à différentes échelles biologiques, de la molécule à l’individu. L’analyse de l’ensemble des résultats permettra de mieux comprendre les effets du tritium, seul ou en mélange, sur la physiologie du poisson