Nathalie Grova
Institut national de la recherche agronomique
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Publication
Featured researches published by Nathalie Grova.
International Dairy Journal | 2002
Nathalie Grova; Cyril Feidt; Claire Laurent; Guido Rychen
Abstract The aim of this work was to characterize phenanthrene, pyrene, benzo(a)pyrene and TCDD transfer to milk, urine and faeces in lactating goats after a single oral ingestion (2.5 10 6 Bq ) of [ 14 C ] phenanthrene , [ 14 C ] pyrene , [ 14 C ] benzo[a]pyrene or [ 14 C ] 2,3,7,8-TCDD. Seven hours after [ 14 C ] PAHs oral ingestion, a radioactivity peak was detected in plasma for all compounds studied. Regarding excretion routes, three specific types of behaviour were noticed: 2,3,7,8-TCDD was mainly excreted in milk (7.8%) and a large part of radioactivity ingested remained in the organism (71.2%). Phenanthrene and pyrene presented a similar behaviour, with a low milk transfer (1.6% and 1.9%, respectively) and a high excretion through urine (40.4% and 11.4%, respectively) suggesting their metabolization. Benzo[a]pyrene was poorly absorbed (88% of the ingested part of this compound was detected in faeces) and radioactivity due to benzo[a]pyrene was not significantly detected in milk (0.2%).
European Journal of Mass Spectrometry | 2000
Nathalie Grova; Claire Laurent; Cyril Feidt; Guido Rychen; François Laurent; Eric Lichtfouse
Polycyclic aromatic hydrocarbon (PAH) levels were studied in grass and milk sampled at two farms, one located in a non-contaminated, rural area, and another located in a urban area close to PAH sources such as highways, busy roads, fuel-powered trains and a steel plant. PAH concentration were measured by gas chromatography coupled to mass spectrometry (GC-MS) using internal deuterated standards. In grasses, unexpectedly, although the sum of PAH concentrations was only slightly higher at the urban farm (83.1 ± 16.1 ng g−1) than the rural farm (51.8 ± 10.6 ng g−1), this difference was not observed for all PAH members. This absence of a striking difference of PAH levels between urban and rural grasses suggests that atmospheric PAH sources, for example, vehicle exhausts and chimney fumes, could be rapidly diluted by winds. In milk, PAH concentrations were not significantly different at urban and rural farms.
Chemosphere | 2008
Nathalie Grova; Henri Schroeder; Sophie Farinelle; Emmanuel Prodhomme; Anne Valley; Claude P. Muller
Abnormal glutamatergic transmission caused by modulation of N-methyl-D-aspartate (NMDA) receptors was demonstrated in animal models chronically exposed to various organic micropollutants. Recent developments in neurobiology have implicated these receptors in the regulation of anxiety. In order to investigate anxiety-related effects of benzo[a]pyrene (B[a]P), Balb/c mice were sub-acutely exposed to B[a]P (0.02-200 mg kg(-1) day(-1), 10 days, i.p.). Their performance was tested in the elevated-plus maze and the hole-board apparatus and the NMDA receptor expression genes (NR1, 2A and 2B subunits) was measured in eight brain regions. Mice treated with 20-200 mg kg(-1) B[a]P showed a disproportionate accumulation of B[a]P and its metabolites (in particular, the toxic 7,8-diol-B[a]P) in the blood and even more in the brain. These mice were less anxious than controls in the hole-board test and the elevated-plus maze. This observation was associated with an overexpression of the NMDA NR1 receptor gene and concomitant decreases of the NR2A and NR2B subunits expression in the hippocampus, the hypothalamus and the cerebellum. In the temporal cortex, a significant dose-related decrease of NR2A was observed whereas the other subunits remained unchanged. In conclusion, a sub-acute exposure to B[a]P (20 and 200 mg kg(-1)) reduced anxiety-related behaviour in adult mice and concomitantly impaired NMDA receptor gene expression in relevant brain regions.
Chemosphere | 2002
Claire Laurent; Cyril Feidt; Nathalie Grova; Didier Mpassi; Eric Lichtfouse; François Laurent; Guido Rychen
Polycyclic aromatic hydrocarbons (PAHs) and dioxins are lipophilic organic pollutants occurring widely in the terrestrial environment. In order to study the PAHs and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) transfer in the food chain, pigs have been fed with milk mixed either with 14C-phenanthrene, with 14C-benzo[a]pyrene or with 14C-TCDD. The analysis of portal and arterial blood radioactivity showed that both PAHs and TCDD were absorbed with a maximum concentration at 4-6 h after milk ingestion. Then, the blood radioactivity decreased to reach background levels 24 h after milk ingestion. Furthermore, the portal and arterial blood radioactivities were higher for phenanthrene (even if the injected load was the lowest) than these of benzo[a]pyrene or these of TCDD, in agreement with their lipophilicity and water solubility difference. Main 14C absorption occurred during the 1-3 h time period after ingestion for 14C-phenanthrene and during the 3-6 h time period for 14C-benzo[a]pyrene and for 14C-TCDD. 14C portal absorption rate was high for 14C-phenanthrene (95%), it was close to 33% for 14C-benzo[a]pyrene and very low for 14C-TCDD (9%). These results indicate that the three studied molecules have a quite different behaviour during digestion and absorption. Phenanthrene is greatly absorbed and its absorption occurs via the blood system, whereas benzo[a]pyrene and TCDD are partly and weakly absorbed respectively. However these two molecules are mainly absorbed via the portal vein.
Toxicology and Applied Pharmacology | 2009
Mario T. Schellenberger; Nathalie Grova; Stéphanie Willième; Sophie Farinelle; Emmanuel Prodhomme; Claude P. Muller
Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-gamma, IL-12, TNF-alpha production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P.
Chemical Research in Toxicology | 2011
Nathalie Grova; Guillaume Salquèbre; Henri Schroeder; Brice M.R. Appenzeller
An efficient and selective method for the quantitative determination of polycyclic aromatic hydrocarbons (PAHs) and their monohydroxylated metabolites (OH-PAHs) in rat brain tissue using gas chromatography tandem (triple quadrupole) mass spectrometry (GC-MS/MS) was developed and validated. The list of molecules investigated comprised the 16 PAHs from the US-EPA list and 53 of their OH-PAHs. Brain extract was submitted to enzymatic hydrolysis, followed by liquid-liquid extraction, and then purified by solid-phase extraction. Limits of quantification ranged from 0.6 to 29 pg/mg and from 0.5 to 30 pg/mg for PAHs and OH-PAHs respectively. The analysis of rat brain samples exposed to PAH mixture (0.01-1 mg/kg, 28 days, ip) demonstrated that this method allowed the detection of 16 PAHs and 28 OH-PAHs out of the 69 analytes investigated. Mean concentrations of PAHs in animal brain samples exposed to 1 mg/kg of PAH mixture ranged from 3.0 ± 2 pg/mg for benzo[b]fluoranthene to 146 ± 29 pg/mg for phenanthrene. Concomitantly, mean concentrations of OH-PAHs ranged from 0.49 ± 0.4 to 26.5 ± 23 pg/mg for 2-OH-chrysene and 1-OH-pyrene respectively. This study proves, for the first time, the bioavailability of most of the PAHs and OH-PAHs in mammalian brain tissue and should provide an important new tool for future neurotoxicological studies.
Vaccine | 2009
Nathalie Grova; Emmanuel Prodhomme; Mario T. Schellenberger; Sophie Farinelle; Claude P. Muller
Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to investigate the effect of specific antibodies on the bioavailability of this ubiquitous carcinogen and its metabolites. After metabolic activation of this prototype carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. Our results showed that this immune prophylactic strategy influences the pharmacokinetic of B[a]P and further studies to investigate their effects on chemical carcinogenesis are warranted.
Journal of Analytical Toxicology | 2017
Nicolas Beauval; Sébastien Anthérieu; Mélissa Soyez; Nicolas Gengler; Nathalie Grova; Michael Howsam; Emilie M. Hardy; Marc Fischer; Brice M.R. Appenzeller; Jean-François Goossens; Delphine Allorge; Guillaume Garçon; Jean-Marc Lo-Guidice; Anne Garat
Electronic cigarette use has raised concern worldwide regarding potential health risks and its position in tobacco cessation strategies. As part of any toxicity assessment, the chemical characterization of e-liquids and their related vapors are among fundamental data to be determined. Considering the lack of available reference methods, we developed and validated several analytical procedures in order to conduct a multicomponent analysis of six e-liquid refills and their resultant vapor emissions (generated by a smoking machine), and compared them with tobacco smoke. We combined several techniques including gas-chromatography, high and ultra-performance liquid chromatography and inductively coupled plasma with mass spectrometry or ultraviolet and flame ionization detection in order to identify the main e-liquid constituents (propylene glycol, glycerol and nicotine), as well as multiple potentially harmful components (trace elements, polycyclic aromatic hydrocarbons (PAHs), pesticides and carbonyl compounds). Regarding propylene glycol, glycerol and nicotine concentrations, the six tested e-liquids comply with the advertised composition and contain only traces of pollutants. Noticeable lower concentrations of trace elements (≤3.4 pg/mL puff), pesticides (<LOQ), PAHs (≤4.1 pg/mL puff) and carbonyls (≤2.11 ng/mL puff) were measured in e-vapors compared to those in cigarette smoke (up to 45.0 pg/mL puff, 8.7 pg/mL puff, 560.8 pg/mL puff and 1540 ng/mL puff, respectively). Although an accurate characterization of electronic cigarette emissions requires further analytical optimizations, our results have shown that vaping exposes the user to lesser amounts of selected toxic components of concern found in some representative French e-cigarette products than does smoking typical conventional cigarettes.
Journal of Chromatography A | 2014
Nathalie Grova; Guillaume Salquèbre; Emilie M. Hardy; Henri Schroeder; Brice M.R. Appenzeller
Since exposure to benzo[a]pyrene is suspected to be associated with several health issues, significant efforts have been made to develop efficient strategies for the assessment of human exposure to this ubiquitous compound. In this context, a method was developed for the analysis of four tetrahydroxylated-benzo[a]pyrene isomers resulting from the hydrolysis of their respective diol-epoxide precursors which are involved in DNA-adduct formation. The analytical sensitivity necessary to reach environmental levels of concentration was obtained by using gas chromatography-tandem mass spectrometry. The recovery determined at the four concentration levels were estimated in average at 83% for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±), 29% for benzo[a]pyrene-r-7,t-8,t-9,t-10-tetrahydrotetrol(±), and 82% for benzo[a]pyrene-r-7,t-8,C-9,c-10-tetrahydrotetrol(±). The coefficient of determination of the calibration curve was above 0.997 for all the analytes investigated and the limit of quantification ranged from 0.5 to 2 adduct/10(8) nucleotides. The precision was between 5.3% and 22.3%. The suitability of the method was firstly evaluated by the analysis of DNA isolated from white blood cells of rats submitted after controlled exposure to benzo[a]pyrene. The four targeted tetra-OH-benzo[a]pyrenes as well as two unknown isomers were detected in all the treated animals. Benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol(±) appeared as the most abundant isomer in both treated and control animals followed by benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±). The method was afterwards applied to the analysis of DNA isolated from white blood cells of human volunteers. The results confirmed that this method was sufficiently sensitive to monitor environmental levels of exposure since all the specimens analyzed were above the limit of quantification for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol(±) and two of them were positive for benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol(±), thereby highlighting interspecies differences in the nature of the tetrahydroxylated-benzo[a]pyrene isomers formed. This study confirms the necessity to focus on all the tetrahydroxylated-benzo[a]pyrene isomers, which could be indicators of benzo[a]pyrene-associated toxicity related to an individuals own metabolism, rather than limit to a single form.
PLOS ONE | 2013
Julie Peiffer; Frédéric Cosnier; Nathalie Grova; Hervé Nunge; Guillaume Salquèbre; Marie Josèphe Decret; B. Cossec; Guido Rychen; Brice M.R. Appenzeller; Henri Schroeder
Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and may contribute to the neurobehavioral alterations induced by the environmental exposure of humans to PAHs. Since no data are available on fluorene neurotoxicity, this study was conducted in adult rats to assess the behavioral toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group) were exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive days, whereas the control animals were exposed to non-contaminated air. At the end of the exposure, animals were tested for activity and anxiety in an open-field and in an elevated-plus maze, for short-term memory in a Y-maze, and for spatial learning in an eight-arm maze. The results showed that the locomotor activity and the learning performances of the animals were unaffected by fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety than controls in the open-field, but not in the elevated-plus maze, which is probably due to a possible difference in the aversive feature of the two mazes. In the same animals, increasing blood and brain levels of fluorene monohydroxylated metabolites (especially the 2-OH fluorene) were detected at both concentrations (1.5 and 150 ppb), demonstrating the exposure of the animals to the pollutant and showing the ability of this compound to be metabolized and to reach the cerebral compartment. The present study highlights the possibility for a 14-day fluorene exposure to induce some specific anxiety-related behavioral disturbances, and argues in favor of the susceptibility of the adult brain when exposed to volatile fluorene.
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École nationale supérieure d'agronomie et des industries alimentaires
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