RESUMEN
Excessive organophosphate flame retardant (OPFR) use in consumer products has been reported to increase human disease susceptibility. However, the adverse effects of tris(2-chloroethyl) phosphate (TCEP) (a chlorinated alkyl OPFR) on the heart remain unknown. In this study, we tested whether cardiac fibrosis occurred in animal models of TCEP (10 mg/kg b.w./day) administered continuously by gavage for 30 days and evaluated the specific role of sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). First, we confirmed that TCEP could trigger cardiac fibrosis by histopathological observation and cardiac fibrosis markers. We further verified that cardiac fibrosis occurred in animal models of TCEP exposure accompanied by SERCA2a, SERCA2b and SERCA2c downregulation. Notably, inductively coupled plasma-mass spectrometry (ICP-MS) analysis revealed that the cardiac concentrations of Ca2+ increased by 45.3% after TCEP exposure. Using 4-Isopropoxy-N-(2-methylquinolin-8-yl)benzamide (CDN1163, a small molecule SERCA activator), we observed that Ca2+ overload and subsequent cardiac fibrosis caused by TCEP were both alleviated. Simultaneously, the protein levels of endoplasmic reticulum (ER) markers (protein kinase R-like endoplasmic reticulum kinase (PERK), inositol requiring protein 1α (IRE1α), eukaryotic initiation factor 2 α (eIF2α)) were upregulated by TCEP, which could be abrogated by CDN1163 pretreatment. Furthermore, we observed that CDN1163 supplementation prevented overactive autophagy induced by TCEP in the heart. Mechanistically, TCEP could lead to Ca2+ overload by inhibiting the expression of SERCA, thereby triggering ER stress and overactive autophagy, eventually resulting in cardiac fibrosis. Together, our results suggest that the Ca2+ overload/ER stress/autophagy axis can act as a driver of cardiotoxicity induced by TCEP.
Asunto(s)
Endorribonucleasas , Retardadores de Llama , Aminoquinolinas , Animales , Autofagia , Benzamidas/metabolismo , Calcio/metabolismo , Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Endorribonucleasas/metabolismo , Endorribonucleasas/farmacología , Factor 2 Eucariótico de Iniciación/metabolismo , Factor 2 Eucariótico de Iniciación/farmacología , Fibrosis , Retardadores de Llama/metabolismo , Retardadores de Llama/farmacología , Humanos , Inositol/metabolismo , Inositol/farmacología , Organofosfatos , Fosfatos/metabolismo , Fosfinas , Proteínas Serina-Treonina Quinasas , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/farmacologíaRESUMEN
Organic phosphorus flame retardants (OPFRs), as a new type of emerging contaminant, have drawn great attention over the last few years, due to their wide distribution in aquatic environments and potential toxicities to humans and living beings. Various treatment methods have been reported to remove OPFRs from water or wastewater. In this review, the performances and mechanisms for OPFRs removal with different methods including adsorption, oxidation, reduction and biological techniques are overviewed and discussed. Each technique possesses its advantage and limitation, which is compared in the paper. The degradation pathways of typical OPFRs pollutants, such as Cl-OPFRs, alkyl OPFRs and aryl OPFRs, are also reviewed and compared. The degradation of those OPFRs depends heavily upon their structures and properties. Furthermore, the implications and future perspectives in such area are discussed. The review may help identify the research priorities for OPFRs remediation and understand the fate of OPFRs during the treatment processes.
Asunto(s)
Contaminantes Ambientales , Retardadores de Llama , Retardadores de Llama/metabolismo , Humanos , Organofosfatos/metabolismo , Fósforo , AguaRESUMEN
This study investigates the occurrence of polybrominated biphenyls (PBBs), a legacy flame retardant, in fishery products such as medicinal grade cod liver oils and canned liver products, sourced from the North Atlantic during 1972-2017. It also assesses the dietary and supplementary (the oils were commonly administered as dietary supplements to children and youth) intake of PBBs from these products. Summed ortho-PBB concentrations ranged from 770 to 1400 pg g-1 fat in the oils and from 99 to 240 pg g-1 whole weight in canned livers, with PBB-49, 52, 101 and 153 accounting for most of these levels. Among the more toxic non-ortho-PBBs, PBB-126 and PBB-169 were not detected, but PBB-77 concentrations ranged from 0.6 to 5.78 pg g-1 fat in the oils and 0.06-0.126 pg g-1 whole weight in canned livers. During 1972-1993, PBB contamination levels were similar for cod liver oils from the Baltic Sea and other North Atlantic regions, but over the timescale of the study, Baltic Sea products appear to show a decline in PBB concentrations. As PBB-77 was the only dioxin-like PBB detected in the samples, the corresponding supplementary (oils, 1972-2001) and dietary (cod liver from 2017) intakes were very low, at < 0.001 pg TEQ kg-1 bm d-1 (or < 0.01 pg TEQ kg-1 bm d-1 upper bound) for the sum of all the measured dioxin-like PBBs -four to six orders of magnitude lower than that arising from other dioxin-like contaminants that were shown to occur in these products, from earlier studies.
Asunto(s)
Aceite de Hígado de Bacalao/química , Alimentos en Conserva/análisis , Gadus morhua/metabolismo , Hígado/química , Bifenilos Polibrominados/análisis , Contaminantes Químicos del Agua/análisis , Adolescente , Animales , Países Bálticos , Niño , Dioxinas/metabolismo , Retardadores de Llama/metabolismo , Humanos , Hígado/metabolismo , Bifenilos Polibrominados/química , Contaminantes Químicos del Agua/químicaRESUMEN
The anthropogenic perturbation of the phosphorus (P) marine biogeochemical cycle due to synthetic organophosphorus compounds remains unexplored. The objective of this work was to investigate the microbial degradation of organophosphate triesters (OPEs), widely used as plasticizers and flame retardants, in seawater and their effects on the physiology and composition of microbial communities. Experiments were performed in July 2014 using surface seawater from the Blanes Bay Microbial Observatory (NW Mediterranean) to which OPEs were added at environmentally relevant concentrations. The concentrations of OPEs in the dissolved-phase generally decreased after 24 hours of incubation at in situ conditions. The fitted first order reaction constants were significantly different than zero for the trihaloalkyl phosphate, tris(2-chloroethyl) phosphate and trialyl phosphate tricresyl phosphate. In general, OPEs triggered an increase of the percentage of actively respiring bacteria, total bacterial activity, and the number of low-nucleic acid bacteria, and a decrease in the percentage of membrane-compromised bacteria. Members of some bacterial groups, in particular Flavobacteria, increased their specific activity, indicating that seawater contains bacteria with the potential to degrade OPEs. In aged seawater that was presumably depleted of labile dissolved organic carbon and inorganic P, alkaline phosphatase activities significantly decreased when OPEs were added, indicating a relief on P stress, consistent with the role of OPEs as potential P sources.
Asunto(s)
Bacterias/metabolismo , Ésteres/metabolismo , Organofosfatos/metabolismo , Fósforo/análisis , Agua de Mar/química , Agua de Mar/microbiología , Contaminantes Químicos del Agua/metabolismo , Bacterias/clasificación , Bacterias/crecimiento & desarrollo , Biotransformación , Retardadores de Llama/metabolismo , Unidades de Cuidados Intensivos , Mar Mediterráneo , Plastificantes/metabolismoRESUMEN
Polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants that are ubiquitously detected in the environment and associated with adverse health outcomes. 6-OH-BDE-47 is a metabolite of the flame retardant, 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), and there is increasing concern regarding its developmental neurotoxicity and endocrine disrupting properties. In this study, we report that early life exposure in zebrafish (Danio rerio) embryos to 6-OH-BDE-47 (50 and 100â¯nM) resulted in higher coiling frequency and significantly increased apoptotic cells in the brain. These effects were partially rescued by overexpression of thyroid hormone receptor ß (THRß) mRNA. Moreover, exposure to 100â¯nM 6-OH-BDE-47 significantly reduced the number of hypothalamic 5-hydroxytryptamine (5-HT, serotonin)-immunoreactive (5-HT-ir) neurons and the mRNA expression of tryptophan hydroxylase 2 (TPH2). These results indicate that 6-OH-BDE-47 affected thyroid hormone regulation through THRß and negatively impacted the nervous system, in turn, affecting coiling behavior. Correlations of these endpoints suggest that coiling frequency could be used as an indicator of neurotoxicity in embryos.
Asunto(s)
Disruptores Endocrinos/toxicidad , Bifenilos Polibrominados/toxicidad , Animales , Apoptosis , Embrión no Mamífero , Disruptores Endocrinos/metabolismo , Retardadores de Llama/metabolismo , Retardadores de Llama/toxicidad , Éteres Difenilos Halogenados/metabolismo , Hipotálamo/metabolismo , Neuronas/efectos de los fármacos , Serotonina/metabolismo , Transducción de Señal , Glándula Tiroides/efectos de los fármacos , Receptores beta de Hormona Tiroidea/metabolismo , Hormonas Tiroideas/metabolismo , Pez Cebra/embriología , Pez Cebra/metabolismoRESUMEN
Decabromodiphenyl ether (BDE209) is a ubiquitous persistent pollutant and has contaminated the environment worldwide. To accelerate BDE209 elimination and reveal the mechanism concerned, the biosurfactant tea saponin enhanced degradation of BDE209 by Brevibacillus brevis was conducted. The results revealed that tea saponin could efficiently increase the solubility of BDE209 in mineral salts medium and improve its biodegradation. The degradation efficiency of 0.5 mg L(-1) BDE209 by 1 g L(-1) biomass with surfactant was up to 55% within 5d. Contact time was a significant factor for BDE209 biodegradation. BDE209 biodegradation was coupled with bioaccumulation, ion release and utilization, and debromination to lower brominated PBDE metabolites. During the biodegradation process, B. brevis metabolically released Na(+), NH4(+), NO2(-) and Cl(-), and utilized the nutrient ions Mg(2+), PO4(3-) and SO4(2-). GC-MS analysis revealed that the structure of BDE209 changed under the action of strain and nonabromodiphenyl ethers (BDE-208, -207 and -206), octabromodiphenyl ethers (BDE-203, -197 and -196) and heptabromodiphenyl ether (BDE-183) were generated by debromination.
Asunto(s)
Brevibacillus/metabolismo , Contaminantes Ambientales/metabolismo , Retardadores de Llama/metabolismo , Éteres Difenilos Halogenados/metabolismo , Saponinas/metabolismo , Tensoactivos/metabolismo , Biodegradación Ambiental , Cromatografía de Gases y Espectrometría de Masas , Halogenación , Saponinas/química , Tensoactivos/química , Té/químicaRESUMEN
Polybrominated diphenyl ethers (PBDEs) are used as additive flame retardants. PBDEs are persistent, bioaccumulative and toxic compounds. They are often detected in sewage sludge which is applied on agricultural soils as fertilizer. The objective of this study was to find out whether plants are able to accumulate and translocate PBDEs. Tobacco (Nicotiana tabacum) and nightshade (Solanum nigrum) were planted in pots containing contaminated sewage sludge and uncontaminated substrate. After 6 months of plant cultivation in sewage sludge up to 15.4 ng g(-1) dw and 76.6 ng g(-1) dw of PBDE congeners--BDE 47, BDE 99 and BDE 100---were accumulated in the nightshade and tobacco tissue, respectively. Corresponding values in plants vegetated in the control garden substrate were 10 times lower. The bioconcentration factors (BCFs) of accumulated congeners were calculated. Tobacco exhibited higher BCFs values and for both plants BCFs values of BDE 47, BDE 99, BDE 100 and BDE 209 negatively correlated with their octanol-water partition coefficients (logK(ow)). The exception was decaBDE (BDE 209) which was accumulated only in tobacco tissue in the concentration of 116.8 ng g(-1) dw. The majority of PBDEs was detected in above-ground plant biomass indicating that both plants have the ability to translocate PBDEs. To our knowledge this is one of the first studies reporting the accumulation of both lower PBDEs and BDE 209 in plants. Our results suggest that absorption, accumulation and translocation of PBDEs by plants and their transfer to the food chain could represent another possible risk for human exposure.