RESUMO
Pharmaceuticals and microplastics constitute potential hazards in aquatic systems, but their combined effects and underlying toxicity mechanisms remain largely unknown. In this study, a simultaneous characterization of bioaccumulation, associated metabolomic alterations and potential recovery mechanisms was performed. Specifically, a bioassay on Mediterranean mussels (Mytilus galloprovincialis) was carried out with polyethylene microplastics (PE-MPLs, 1 mg/L) and citalopram or bezafibrate (500 ng/L). Single and co-exposure scenarios lasted 21 days, followed by a 7-day depuration period to assess their potential recovery. PE-MPLs delayed the bioaccumulation of citalopram (lower mean at 10 d: 447 compared to 770 ng/g dw under single exposure), although reaching similar tissue concentrations after 21 d. A more limited accumulation of bezafibrate was observed overall, regardless of PE-MPLs co-exposure (Assuntos
Mytilus
, Poluentes Químicos da Água
, Animais
, Microplásticos/metabolismo
, Polietileno/metabolismo
, Bezafibrato/metabolismo
, Bezafibrato/farmacologia
, Plásticos/metabolismo
, Citalopram/metabolismo
, Citalopram/farmacologia
, Bioacumulação
, Preparações Farmacêuticas/metabolismo
, Poluentes Químicos da Água/análise
RESUMO
BACKGROUND: Phthalic acid esters are widely used in the manufacture of plastics. Numerous studies have shown that these phthalates impair testicular testosterone production in the rat. However, the scarce and contradictory data concerning humans have cast doubt over whether these compounds are also anti-androgenic in man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human testis and a human cell line. METHODS: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with DEHP or MEHP. The effects of ketoconazole, used as a reference molecule, were also assessed. RESULTS: In both models, DEHP and MEHP significantly inhibited testosterone production. The effects of both phthalates appeared to be specific for steroidogenesis, as INSL3 production by Leydig cells was not altered. Furthermore, the phthalates of interest had no effect on inhibin B production by Sertoli cells or on germ cell apoptosis. As only a small fraction of the phthalates added was found in the testis explants, and as these compounds were found to be metabolized, we estimate that the anti-androgenic effects observed occurred at concentrations of phthalates that are of the same order of magnitude as exposures reported in the literature for men. CONCLUSIONS: We provide the first evidence that DEHP and MEHP can inhibit testosterone production in the adult human testis. This is consistent with recent epidemiological findings of an inverse correlation between exposure to MEHP and testosterone concentrations.
Assuntos
Dietilexilftalato/análogos & derivados , Dietilexilftalato/toxicidade , Testículo/efeitos dos fármacos , Testosterona/biossíntese , Apoptose , Linhagem Celular , Humanos , Inibinas/biossíntese , Insulina/metabolismo , Cetoconazol/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Proteínas/metabolismo , Células de Sertoli/metabolismo , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Testículo/metabolismo , Técnicas de Cultura de TecidosRESUMO
RATIONALE: The control of forbidden anabolic practices in cattle in the European Union has become challenging since endogenous compounds such as estradiol derivatives can potentially be used as growth promoters. Due to the great difficulty in establishing a reference threshold value for endogenous steroids, the direct detection of steroid esters in hair is an efficient strategy for the detection of 'natural' steroid abuse in cattle. METHODS: The present study aimed to develop and validate according to the current European standards a specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) analytical strategy to monitor estrogen esters in bovine hair. The analysis was performed by positive ion electrospray ionisation (ESI+) after dansylation. Two acquisition modes were then assessed: single reaction monitoring and precursor ion scanning. RESULTS: The results showed that the introduction of a dansylation step strongly improves the sensitivity of the detection of estradiol-17-esters by LC/(ESI+)-MS/MS. The CCα values are in the range 1-10 ng g(-1) after optimisation, except for estradiol decanoate for which the derivatisation is not efficient. In addition, this LC/MS/MS approach makes it possible to carry out a precursor ion scan to screen for the presence of these estradiol 17-esters in hair samples. CONCLUSIONS: Based on the specific product ions, i.e. m/z 255 in native conditions or m/z 171 after dansylation, this strategy has the advantage of detecting any (un)known estradiol ester and of giving access to the [M + H](+) ion of the suspected ester through only a single analysis.
Assuntos
Cromatografia Líquida/métodos , Ésteres/análise , Estradiol/análogos & derivados , Estradiol/análise , Cabelo/química , Espectrometria de Massas em Tandem/métodos , Animais , Bovinos , Compostos de Dansil/química , Ésteres/classificação , Estradiol/classificação , União Europeia , Limite de Detecção , Reprodutibilidade dos TestesRESUMO
Exposure of aquatic organisms to antidepressants is currently well documented, while little information is available on how wild organisms cope with exposure to these pharmaceutical products. Studies on antidepressant metabolism in exposed organisms could generate information on their detoxification pathways and pharmacokinetics. The goal of this study was to enhance knowledge on the metabolism of venlafaxine (VEN)-an antidepressant frequently found in aquatic ecosystems-in Mytilus galloprovincialis, a bivalve that is present worldwide. An original tissue extraction technique based on the cationic properties of VEN was developed for further analysis of VEN and its metabolites using targeted and non-targeted approaches. This extraction method was assessed in terms of recovery and matrix effects for VEN metabolites. Commercial analytical standards were applied to characterize metabolites found in mussels exposed to 10 µg/L VEN for 3 and 7 days. Targeted and non-targeted approaches using liquid chromatography (LC) combined with high-resolution mass spectrometry (HRMS) were implemented to screen for expected metabolites based on the literature on aquatic species, and for metabolites not previously documented. Four venlafaxine metabolites were identified, namely N-desmethylvenlafaxine and O-desmethylvenlafaxine, which were clearly identified using analytical standards, and two other metabolites revealed by non-target analysis. According to the signal intensity, hydroxy-venlafaxine (OH-VEN) was the predominant metabolite detected in mussels exposed for 3 and 7 days.
Assuntos
Mytilus , Poluentes Químicos da Água , Animais , Cromatografia Líquida , Succinato de Desvenlafaxina , Ecossistema , Cloridrato de Venlafaxina , Poluentes Químicos da Água/análiseRESUMO
Sub-Saharan urban centers have to tackle high population growth, lack of sanitation infrastructures and the need for good quality water resources. To characterize the impacts of anthropization on the water resources of the capital of Cameroon (Yaoundé), a multi-disciplinary approach was used in ten sub-watersheds (peri-urban and urban) of the Méfou watershed. Pharmaceutical residues were used as tracers of surface and groundwater contamination caused by the release of domestic wastewater from pit latrines and landfills. A water use survey was conducted in the vicinity of the sampling sites to better assess water use, treatment and management. Available land use and hydro-geomorphological data completed characterization of the sub-watersheds. The combined data showed that natural features (elevation, slope, and hydrography) and human activities (land use) favor rainfall-runoff events and hence surface water contamination. Pharmaceutical monitoring revealed contamination of both surface and groundwater especially in the urban sub-watersheds. Analgesics/anti-inflammatory drugs and anti-epileptic carbamazepine were the most frequently found compounds (in up to 91% of water samples) with concentrations of acetaminophen reaching 5660â¯ng/L. In urban sub-watersheds, 50% of the groundwater sites used for drinking water were contaminated by diclofenac (476-518â¯ng/L), carbamazepine (263-335â¯ng/L), ibuprofen (141-276â¯ng/L), sulfamethoxazole (<2-1285â¯ng/L) and acetaminophen (110-111â¯ng/L), emphasizing the need for a deeper understanding of the interactions between surface and groundwater. The use of groundwater as drinking water by 68% of the total population surveyed raises concerns about population exposure and potential health risks. This case study highlights the need for strategies to limit contamination of the water resource given the predicted future expansion of Sub-Saharan urban centers.
Assuntos
Monitoramento Ambiental , Água Subterrânea/química , Preparações Farmacêuticas/análise , Poluentes Químicos da Água/análise , Poluição da Água/estatística & dados numéricos , Abastecimento de Água/estatística & dados numéricos , África do Norte , Saneamento , Qualidade da ÁguaRESUMO
Lipids represent an extended class of substances characterized by such high variety and complexity that makes their unified analyses by liquid chromatography coupled to either high resolution or tandem mass spectrometry (LC-HRMS or LC-MS/MS) a real challenge. In the present study, a new versatile methodology associating ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) have been developed for a comprehensive analysis of lipids. The use of polarity switching and "all ion fragmentation" (AIF) have been two action levels particularly exploited to finally permit the detection and identification of a multi-class and multi-analyte extended range of lipids in a single run. For identification purposes, both higher energy collision dissociation (HCD) and in-source CID (collision induced dissociation) fragmentation were evaluated in order to obtain information about the precursor and product ions in the same spectra. This approach provides both class-specific and lipid-specific fragments, enhancing lipid identification. Finally, the developed method was applied for differential phenotyping of serum samples collected from pet dogs developing spontaneous malignant mammary tumors and health controls. A biological signature associated with the presence of cancer was then successfully revealed from this lipidome analysis, which required to be further investigated and confirmed at larger scale.
Assuntos
Neoplasias da Mama/sangue , Cromatografia Líquida de Alta Pressão/métodos , Lipídeos/análise , Lipídeos/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Cães , FemininoRESUMO
Metabolic fingerprinting is an untargeted approach which has not yet been undertaken to investigate cheese. This study is a proof of concept, concerning the ability of mass spectrometry (MS) metabolic fingerprinting to investigate modifications induced by bacterial metabolism in cheese over time. An ultrafiltrated milk concentrate was used to manufacture model cheeses inoculated with Lactococcus lactis LD61. Metabolic fingerprints were acquired after 0, 8 and 48h from two different fractions of the metabolome: the water-soluble fraction using liquid chromatography-high resolution-MS and a volatile fraction using gas chromatography-MS. Metabolic fingerprints differed significantly over time. Forty-five metabolites were identified, including well-known cheese metabolites, such as 12 amino acids and 25 volatile metabolites, and less studied ones, such as four vitamins, uric acid, creatine and l-carnitine. These results showed the relevance of cheese MS fingerprinting to generate new findings and to detect even slight differences between two conditions.
Assuntos
Queijo/análise , Queijo/microbiologia , Lactococcus lactis/metabolismo , Espectrometria de Massas/métodos , Metabolômica/métodos , Animais , Lactococcus lactis/química , Leite/química , Leite/microbiologia , Modelos BiológicosRESUMO
The occurrence of the main steroid hormones (oestrone, 17alpha-oestradiol, 17beta-oestradiol, 17alpha-testosterone, 17beta-testosterone, dehydroepiandrosterone, 4-androstenedione), especially in milk and eggs, was investigated. An analytical method based on GC-MS/MS was developed for steroid measurement at an ultra-trace level in food products. The limits of detection for oestrogens were about 5 and 30 ng kg(-1) in milk and eggs, respectively. For androgens, the limits of detection were around 10 and 50 ng kg(-1) in milk and eggs, respectively. The method was applied to milk and egg samples collected in a French supermarket. In milk, oestrone was found at levels between 100 and 300 ng l(-1), while 17beta-oestradiol levels were estimated to be near 20 ng l(-1). 17alpha-testosterone was found to be from 50 ng l(-1) in skimmed milk to 85 ng l(-1) in whole milk. In egg samples, oestrone and 17beta-oestradiol were found at 1.5 and 0.9 microg kg(-1), respectively, while 17alpha-oestradiol was found to be in lower concentrations (i.e. around 0.55 microg kg(-1)). Regarding androgens, 17alpha- and 17beta-testosterone were estimated at 1.9 and 1.3 microg kg(-1), respectively. These results represent a first attempt to estimate the food exposure to steroid hormones. In the future, the collection of additional data should permit the comparison between this exogenous dietary intake and the daily endogenous production in pre-pubertal children as a basis of risk assessment regarding endocrine disruption linked to these molecules for this critical population.
Assuntos
Androgênios/análise , Ovos/análise , Estrogênios/análise , Leite/química , Animais , Criança , Disruptores Endócrinos/análise , França , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Concentração Máxima PermitidaRESUMO
A comparative study of the cranial morphologies of cetaceans and of rodents that use their incisors for burrowing brings out morphological convergences concerning the supra-occipital bone. These phyletically very remote groups are both subject to the same mechanical constraint, viz. the need for the spinal column to be aligned with the anteroposterior axis of the skull. This constraint, which is related to swimming in cetaceans and burrowing in rodents, entails three major points of convergence: 1) a clearly backward facing foramen magnum; 2) a shortened or even greatly shortened neck, sometimes with cervical vertebrae fused together; and 3) an uprighted or even forward tilted supra-occipital bone.
Assuntos
Cetáceos/anatomia & histologia , Osso Occipital/anatomia & histologia , Roedores/anatomia & histologia , Crânio/anatomia & histologia , Animais , Filogenia , Coluna Vertebral/anatomia & histologiaRESUMO
A study of voles (Arvicolidae, Rodentia) from Gansu (China) designed to identify a potential host of Echinococcus multilocularis, responsible for human alveolar echinococcosis, leads to a general analysis of Microtus limnophilus population karyotypes, M1 of M. oeconomus populations from all of Eurasia and of M. limnophilus of Mongolia. The Microtus of Gansu belonging to the nominal subspecies M. limnophilus limnophilus (2n = 38; NF = 58) differs markedly in size and shape of M1 from the M. limnophilus of Mongolia, which must therefore be considered as a new subspecies M. limnophilus of malygini nov. ssp. (2n = 38; NF = 60) and the M. oeconomus of Mongolia should be ranked as M. oeconomus kharanurensis nov. ssp. (2n = 30; NF = 60).