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1.
Environ Pollut ; 254(Pt B): 113105, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476675

RESUMO

Soil organisms are exposed to natural and anthropogenic stressors, such as xenobiotics. However, to simplify and make laboratory experiments easily reproducible, natural stressors are often excluded from ecotoxicological studies and risk assessment. This might underestimate the effect of chemicals, since synergistic interactions between chemicals and natural stressors might occur, creating a more severe impact than expected. Several studies have addressed simultaneous exposure to natural and chemical stressors, but very little is known of about the persistence of these interactions during recovery. Here, we examined if recovery after chemical stress exposure was important for the ability of springtails (Folsomia candida) to tolerate subsequent drought- and heat stress. Nonylphenol (NP) and phenanthrene (PHE) was tested and their isolated toxicity resulted in LC50 values of 206 mg NP kg-1 dry soil and 109 mg PHE kg-1 dry soil in a 7-day test. Elimination of NP and PHE was rapid and only trace amounts remained in springtail tissues after 3-7 days of recovery. Isolated studies of drought and heat shock on Folsomia candida resulted in a lethal effect for 50% of the animals (LRH50) at a relative humidity (RH) of 97.9%, and 190 min at 34 °C was shown to be lethal for 50% of the test species (LT50). The results showed, as expected, significant synergistic interactions between the effects of the chemicals and the effects of drought and heat stress. The negative effects of NP and PHE on the drought tolerance disappeared within 7 days post exposure. Springtails exposed to PHE also recovered their heat tolerance within 7 days post exposure, while NP exposed animals had not fully recovered their heat tolerance 14 days after exposure. Overall, a recovery period post chemical exposure was found to be very important for springtails in order to cope with natural stressors like heat and drought.


Assuntos
Artrópodes/efeitos dos fármacos , Resposta ao Choque Térmico , Fenantrenos/toxicidade , Fenóis/toxicidade , Poluentes do Solo/toxicidade , Animais , Artrópodes/fisiologia , Secas , Solo
2.
Sci Total Environ ; 686: 903-914, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31412527

RESUMO

Olive mill wastewater (OMW) as a by-product of olive oil extraction process has significant polluting properties mainly related to high organic load, increased COD/BOD ratio, high phenolic content and relatively acidic pH. Raw OMW from Slovenian Istria olive oil mill and its polar fraction were investigated in this study. Chemical characterization of OMW polar fraction identified tyrosol as the most abundant phenolic product, followed by catechol. Lethal and sub-lethal effects of OMW matrix and its polar fraction were tested using a battery of bioassays with model organisms: bacteria Vibrio fischeri, algae Chlorella vulgaris, water fleas Daphnia magna, zebrafish Danio rerio embryos, clover Trifolium repens and wheat Triticum aestivum. Raw OMW sample was the most toxic to V. fischeri (EC50 = 0.24% of OMW sample final concentration), followed by D. magna (EC50 = 1.43%), C. vulgaris (EC50 = 5.20%), D. rerio (EC50 = 7.05%), seeds T. repens (EC50 = 8.68%) and T. aestivum (EC50 = 11.58%). Similar toxicity trend was observed during exposure to OMW polar fraction, showing EC50 values 2.75-4.11 times lower comparing to raw OMW. Tested samples induced also sub-acute effects to clover and wheat (decreased roots, sprouts elongation); and to zebrafish embryos (increased mortality, higher abnormality rate, decreased hatching and pigmentation formation rate). A comprehensive approach using a battery of bioassays, like those used in this study should be applied during ecotoxicity monitoring of untreated and treated OMW.


Assuntos
Resíduos Industriais/efeitos adversos , Azeite de Oliva , Fenóis/toxicidade , Águas Residuárias/toxicidade , Poluentes Químicos da Água/toxicidade , Aliivibrio fischeri/efeitos dos fármacos , Animais , Chlorella vulgaris/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Azeite de Oliva/química , Fenóis/análise , Testes de Toxicidade , Trifolium/efeitos dos fármacos , Triticum/efeitos dos fármacos , Peixe-Zebra
3.
Environ Pollut ; 254(Pt A): 112921, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394349

RESUMO

The associations between bisphenol analogues (BPs) exposure and oxidative damage was explored in this 3-year longitudinal study of 275 school children in East China. Nine BPs in first morning urine samples were measured to assess BPs exposure, and 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxo-7,8-dihydroguanosine (8-OHG) were measured as biomarkers of oxidative DNA and RNA damage. Linear mixed model (LMM) was used for repeated measures analysis. School children were mainly exposed to BPA, BPS, BPF, and BPAF (detection frequencies: 97.9%, 42.2%, 13.3%, and 12.8%) with median concentrations of 1.55, 0.355, 0.236 and 0.238 µg g-1Cre, respectively. An interquartile range (IQR) increase in urinary BPA was significantly associated with 12.9% (95% CI: 6.1%, 19.6%) increase in 8-OHdG and 19.4% (95% CI: 11.7%, 27.1%) increase in 8-OHG, and for total of BPs (the sum of BPA, BPS, BPF, and BPAF), they were 17.4% (95% CI: 8.9%, 26.0%) for 8-OHdG and 25.9% (95% CI: 16.1%, 35.7%) for 8-OHG, respectively. BPS was positively associated with 8-OHG, but not with 8-OHdG. The study found positive associations of urinary levels of BPA and total BPs with 8-OHdG and 8-OHG and indicated that BPs exposure might cause oxidative RNA damage.


Assuntos
Compostos Benzidrílicos/urina , Dano ao DNA , Desoxiguanosina/análogos & derivados , Exposição Ambiental/análise , Poluentes Ambientais/urina , Fenóis/urina , Compostos Benzidrílicos/toxicidade , Biomarcadores/urina , Criança , China , DNA , Desoxiguanosina/urina , Poluentes Ambientais/toxicidade , Humanos , Estudos Longitudinais , Oxirredução , Estresse Oxidativo , Fenóis/toxicidade , RNA , Projetos de Pesquisa
4.
Sci Total Environ ; 687: 877-884, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412491

RESUMO

With the increasing use of bisphenol F (BPF) as BPA alternative, BPF are widely distributed in multiple environment media. Our previous study demonstrated that BPF possess equivalent toxicity towards zebrafish as BPA, while its toxic mechanism remains largely unknown. To investigate the mechanisms mediating the developmental effects of BPF, zebrafish embryos were exposed to 0.0005, 0.5, and 5.0 mg/L BPF. Morphological examination indicated that BPF exposure led to depigmentation, decreased heart rate, inhibited spontaneous movement, hatch inhibition, and spinal deformation. Motor neuron-green fluorescence zebrafish assay indicated that exposure to 0.5 or 5.0 mg/L BPF affected embryonic motor neuron development, which is consistent with the spinal defect and spontaneous movement inhibition. Transcriptomic analysis showed that genes associated with the observed symptoms, including neuron development (ngln2a, socs3a, fosb), cardiac development (klf2a), and spinal deformation (ngs, col8a1a, egr2a), were down-regulated after exposure to either 0.0005 (environmental relevant concentration) or 0.5 mg/L BPF. This partially explained the mechanisms underlying the effects of BPF. In conclusion, BPF had the potential to affect zebrafish development even at environmental level through down-regulating associated genes.


Assuntos
Compostos Benzidrílicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Larva , Peixe-Zebra/fisiologia
5.
Ecotoxicol Environ Saf ; 183: 109492, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31421534

RESUMO

Bisphenol A (BPA) is an artificial xenoestrogen widely used in consumer products containing polycarbonate plastics and epoxy resins. Exposure to BPA occurs through various channels, including ingestion of contaminated food and water. Autophagy is an important catabolic pathway that plays an important role in liver lipid metabolism. Evidence suggests that BPA exposure causes abnormal lipid droplet accumulation in liver, but the mechanism remains unknown. Here, we investigate the function of BPA in lipid metabolism and autophagy. BPA exposure increases lipid droplet and ROS accumulation which is accompanied by a defect in the fusion of the autophagosome to the lysosome. BPA exposure decreases the translocation of Stx17 to lysosome resulting in the autophagogome-lysosome fusion defect. There is no defect in the formation of the autophagosome indicated by increased LC3-II, p62 level, GFP/mRFP-LC3 ratios and decreased colocalization between LAMP2 with LC3. Mechanistically, BPA exposure reduces autophagy SNARE complex formation. Promoting autophagy by autophagy inducer (Torin2) partially reverses lipid droplet accumulation caused by BPA exposure. In summary, our results demonstrate BPA exposure inhibits autophagy resulting in decreased lipid droplet degradation and increased ROS levels. These results also provide a novel implication between autophagosome-lysosome fusion.


Assuntos
Autofagossomos/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Gotículas Lipídicas/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Fenóis/toxicidade , Animais , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular , Células HEK293 , Células HeLa , Humanos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos , Naftiridinas/farmacologia , Proteínas Qa-SNARE/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
Sci Total Environ ; 685: 1294-1305, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31272786

RESUMO

Bisphenol A (BPA) is an abundant environmental contaminant and studies have shown the presence of BPA in the urine of over 90% of population tested in Canada and USA. In addition to its reported harmful effects, there is concern for its transgenerational effects. For a compound to induce transgenerational effect, an epigenetic mark should be mitotically and meiotically stable without reprogramming in primordial germ cells and post fertilization embryos. In the present study, female zebrafish were treated with an environmental dose (20 µg/L) of BPA and then crossed with untreated males. To assess epigenetic effects, transcript levels of several genes involved in female reproduction were measured in adult and in 24 hpf embryos up to F3 generation. Exposure to BPA affected adult female fertility up to F2 generation. In F0, F1 and F2 ovaries transcript levels for several genes involved in reproduction, including esr, star, lhcgr and fshr were affected. To investigate epigenetic mechanisms of gene expression modulation, we studied promoter DNA methylation. Among genes involved in gonadal differentiation, amh transcript level was reduced in 24 hpf embryos, up to the F3 generation. Variation in amh transcript level was associated with hyper-methylation of its promoter and changes in H3K4me3/H3K27me3 enrichment, coherent with gene silencing. The findings provide evidence for transgenerational effects of BPA in zebrafish and demonstrate that amh is susceptible to stable epigenetic alterations. CAPSULE: Transgenerational effects of BPA on female reproductive physiology.


Assuntos
Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Metilação de DNA , Epigênese Genética , Feminino , Histonas , Regiões Promotoras Genéticas , Peixe-Zebra
7.
Environ Sci Pollut Res Int ; 26(25): 26332-26338, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286379

RESUMO

Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in the production of polycarbonate plastics and epoxy resins, which has been previously linked to diabetes among non-Hispanic populations. As part of a case control study for breast cancer, only controls with BPA information were included in this report. The final sample size comprises 70 self-reported diabetics and 334 non-diabetics. Urinary free bisphenol A (BPA-F) (µg/L) was determined by solid-phase extraction and HPLC/FLD analysis. Logistic regression models were used to evaluate the association between BPA-F and self-reported diabetes. After adjusting by age, urinary BPA-F (4.06-224.53 µg/g creatinine) was associated with diabetes exposure (OR = 1.85; 95% CI 1.04, 3.28) compared with women in the reference category (0.67-4.05 µg/g creatinine). BPA may be an environmental cofactor of diabetes. More studies are needed to confirm this result, especially in Hispanic populations.


Assuntos
Compostos Benzidrílicos/toxicidade , Diabetes Mellitus/induzido quimicamente , Exposição Ambiental/efeitos adversos , Fenóis/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Benzidrílicos/urina , Estudos de Casos e Controles , Creatinina/urina , Diabetes Mellitus/urina , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/urina , Feminino , Humanos , México , Pessoa de Meia-Idade , Fenóis/urina , Fatores de Risco
8.
Chemosphere ; 235: 543-549, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31279116

RESUMO

PURPOSE: Nonylphenol (NP) is one widely distributed representative of environmental estrogens that disturb reproductive activities, bone metabolism and brain function through interfering diverse signal pathways leading to hormone metabolic dysfunctions, immunologic derangement, and tumorigenesis. Few of previous studies have observed the subacute toxicity on rodents, and little has been focused on the mechanism underneath the toxicities observed. METHODS: The 32 male Sprague-Dawley (SD) rats were randomly divided into four groups, the negative control group (corn oil) NP low, medium and high dose groups [30, 90, 270 mg/(kg·d)]. SD rats administrated with different dosage of NP every other day for 28d. Elisa and RT-PCR was employed to observe estrogen metabolism markers or mRNA expressions. RESULTS: In serum, NP exposure caused testosterone (T) (p < 0.001), progesterone (PROG) (p < 0.05) and estrone (E1) (p < 0.05) increased. In testicle, NP exposure caused T (p < 0.001), PROG (p < 0.05), E1 (p < 0.05), 17ß-estradiol (E2) (p < 0.05) and ERα mRNA (p < 0.01) increased, while P450 aromatizing enzyme (p < 0.001) decreased in NPL and ERß mRNA (p < 0.001) decreased in NPM and NPH. In liver, NP exposure caused 17ß-HSD2 mRNA (p < 0.01) increased, while P450 aromatizing enzyme decreased (p < 0.05). CONCLUSION: NP exposure exhibited general and estrogenic toxicity in rats through disturbing estrogen secretion network and estrogen receptor expression network, inducing abnormal metabolism of estrogen, whether in serum, liver and testicle.


Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios/metabolismo , Fígado/metabolismo , Fenóis/toxicidade , Testículo/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrona/metabolismo , Feminino , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Estrogênicos/metabolismo , Testosterona/metabolismo , Testes de Toxicidade
9.
Sci Total Environ ; 689: 1012-1022, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31280147

RESUMO

The etiology of depression is not known, it is thought that endocrine-disrupting chemicals (EDCs) contribute to the disease. Results of our previous research have shown that nonylphenol (NP), a well-known EDC, has neurotoxic effects, however, whether NP can induce depressive behavior by affecting synaptic plasticity has not yet been clearly elucidated. The depressive behavior induced by subchronic exposure to NP and its effect on the neuronal synaptic plasticity in rats are dynamically observed. Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C, corn oil), NP group (NP, 4 mg/kg), and depression model group (D, corticosterone 20 mg/kg). There were 8 rats in each group. The depressive behavior of rats was tested by sucrose preference test, open-field test, and forced swimming test once a month for 3 months. The serum levels of brain-derived neurotrophic factor (BDNF) and corticosterone were detected by ELISA assay, and cellular morphological changes were observed by hematoxylin-eosin (HE) staining. The number of nerve cells, the length of dendrites, and the density of dendritic spines were observed by Golgi staining, and the synaptic cleft width, the postsynaptic density (PSD) thickness, and the synaptic interface curvature were observed by transmission electron microscope. Compared with the control group, the consumption of sucrose solution decreased in the NP group at the 2nd and 3rd month compared to the 1st month (F = 9.887, P = 0.002). The number of central square entries, the central square duration, and the total distance of movement were all decreased, and the decreasing degrees at the 3rd month were greater than those at the 1st month (F = 21.191, P < 0.001; F = 9.836, P = 0.002). The time of immobility for the NP group at the 1st month was higher than that in the control group (F = 6.912, P = 0.002). The expression of BDNF in the NP-treated group was higher than the control, while the expression of corticosterone in the NP-treated group was lower than the control. In the NP group, the cytoplasm of nerve cells contracted and appeared disordered. The neuron arrangement was disordered, and the number of cells, the length of the apex, the length of the basal dendrites, and the dendritic spine density were all lower in the NP group than those in the control group. The PSD thickness, the synaptic cleft width, and synaptic interface curvatures were all decreased in the NP group when compared to the control group. Subchronic exposure to 4 mg/kg NP led to depressive behavior in rats, and the depressive behavior and alterations in synaptic plasticity were more obvious with longer exposure time.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Depressão/fisiopatologia , Disruptores Endócrinos/toxicidade , Glucocorticoides/sangue , Plasticidade Neuronal/efeitos dos fármacos , Fenóis/toxicidade , Animais , Depressão/induzido quimicamente , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
10.
Sci Total Environ ; 689: 1201-1211, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31358486

RESUMO

Senescence is an irreversible process that is a characteristic of age-associated disease like Type 2 diabetes (T2D). Bisphenol-A (BPA), one of the most common endocrine disruptor chemicals, received special attention in the development of insulin resistance and T2D. To understand the role played by BPA in cellular senescence under metabolic stress, zebrafish embryos were exposed to BPA in the absence and presence of hyperglycaemia. Transcriptional levels of the senescence markers p15, p53, Rb1 and ß-galactosidase were increased when BPA was combined with metabolic stress. In addition, zebrafish embryos that were exposed to combination of hyperglycaemia and BPA exhibited increased levels of apoptosis. However, cellular senescence remained induced by a combination of hyperglycaemia and BPA exposure even in the absence of a translated p53 protein suggesting that senescence is primarily independent of it but dependent on the p15-Rb1 pathway under our experimental conditions. To confirm that our results hold true in adult mammalian tissues, we validated our embryonic experiments in an adult mammalian metabolic model of skeletal muscle cells. Our work reveals a novel and unique converging role of senescence and apoptosis axis contributing to glucose dyshomeostasis. Thus, we conclude that BPA exposure can exacerbate existing metabolic stress to increase cellular senescence that leads to aggravation of disease phenotype in age-associated diseases like type 2 diabetes.


Assuntos
Compostos Benzidrílicos/toxicidade , Senescência Celular/genética , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Proteína Supressora de Tumor p53/genética , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/fisiologia , Animais , Embrião não Mamífero/fisiologia , Estresse Fisiológico , Proteína Supressora de Tumor p53/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
11.
Aquat Toxicol ; 214: 105232, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271907

RESUMO

Understanding the mode of action of the different pollutants in human and wildlife health is a key step in environmental risk assessment. The aim of this study was to determine signatures that could link morphological phenotypes to the toxicity mechanisms of four Endocrine Disrupting Chemicals (EDCs): bisphenol A (BPA), perfluorooctanesulfonate potassium salt (PFOS), tributyltin chloride (TBT), and 17-ß-estradiol (E2). Zebrafish (Danio rerio) eleutheroembryos were exposed from 2 to 5 dpf to a wide range of BPA, PFOS, TBT and E2 concentrations. At the end of the exposures several morphometric features were assessed. Common and non-specific effects on larvae pigmentation or swim bladder area were observed after exposures to all compounds. BPA specifically induced yolk sac malabsorption syndrome and altered craniofacial parameters, whereas PFOS had specific effects on the notochord formation presenting higher rates of scoliosis and kyphosis. The main effect of E2 was an increase in the body length of the exposed eleutheroembryos. In the case of TBT, main alterations on the morphological traits were related to developmental delays. When integrating all morphometrical parameters, BPA showed the highest rates of malformations in terms of equilethality, followed by PFOS and, distantly, by TBT and E2. In the case of BPA and PFOS, we were able to relate our results with effects on the transcriptome and metabolome, previously reported. We propose that methodized morphometric analyses in zebrafish embryo model can be used as an inexpensive and easy screening tool to predict modes of action of a wide-range number of contaminants.


Assuntos
Embrião não Mamífero/anatomia & histologia , Embrião não Mamífero/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/embriologia , Ácidos Alcanossulfônicos/toxicidade , Animais , Compostos Benzidrílicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/farmacologia , Estradiol/toxicidade , Fluorcarbonetos/toxicidade , Humanos , Larva/efeitos dos fármacos , Análise dos Mínimos Quadrados , Análise Multivariada , Fenóis/toxicidade , Análise de Componente Principal , Análise de Sobrevida , Testes de Toxicidade , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade
12.
Chemosphere ; 235: 616-625, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31276874

RESUMO

Endocrine-disrupting chemicals encompass a variety of chemicals that may interfere with the endocrine system and produce negative effects on organisms. Among them, bisphenol A is considered a major pollutant in numerous countries. The harmful effects of BPA on environmental and human health are intensely studied. However, the effects of BPA on terrestrial insects are still poorly investigated, despite that several plants can accumulate BPA in their tissues, leading to potential contamination of herbivorous insects. Here, we used the leafworm Spodoptera littoralis, a polyphagous species, to study BPA effects on post-embryonic development. We studied the effects of BPA ingestion at environmental doses (e.g., 0.01, 0.1, and 1 µg/g of BPA) and high doses (e.g., 25 µg/g) on larval weight and stage duration, pupal length and sex ratio. BPA effects were investigated in more detail during the last larval instar, a crucial period for preparing pupation and metamorphosis, which are under endocrine control. We monitored the haemolymph concentration of ecdysteroids, hormones controlling moult and metamorphosis, as well as the expression levels of several nuclear receptors involved in the ecdysteroid signalling pathway. Our integrative study showed that, upon exposure doses, BPA can induce various effects on the viability, developmental time, growth and sex ratio. These effects were correlated with a delay of the ecdysteroid peak during the last larval instar and a modification of expression of EcR, USP, E75AB, E75D and Br-c. We provide new evidence about the events that occur after BPA exposure in insect contaminated by food ingestion.


Assuntos
Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Fenóis/toxicidade , Spodoptera/efeitos dos fármacos , Animais , Ecdisteroides , Disruptores Endócrinos/metabolismo , Poluentes Ambientais/metabolismo , Gossypium , Larva/efeitos dos fármacos , Metamorfose Biológica/efeitos dos fármacos , Pupa/efeitos dos fármacos , Spodoptera/crescimento & desenvolvimento
13.
Chem Commun (Camb) ; 55(60): 8876-8879, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31286121

RESUMO

Here we report template-free synthesis of imine-linked calix[4]arene hollow nanocapsules and their utility in the effective delivery of a poorly soluble cancer drug into tumor cells. These stimuli-responsive nanocapsules show high drug loading and release which resulted in a 40-fold higher cytotoxicity for breast cancer cell line over normal cells.


Assuntos
Antineoplásicos/farmacologia , Calixarenos/química , Camptotecina/farmacologia , Portadores de Fármacos/química , Nanocápsulas/química , Fenóis/química , Antineoplásicos/química , Calixarenos/síntese química , Calixarenos/toxicidade , Camptotecina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Nanocápsulas/toxicidade , Fenóis/síntese química , Fenóis/toxicidade
14.
Chemosphere ; 234: 682-689, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31234085

RESUMO

Bisphenol A (BPA) is widely used in the production of epoxy resins and polycarbonate plastics. Under harsh situations, these plastics likely desorb BPA, which then can seep into the environment. Various concentrations of BPA have been detected in most biological fluid. However, there is paucity of information on the detrimental effects of BPA and its subsequent cellular events in chronic kidney disease (CKD). Hence, in this in vitro study, we aimed to investigate the effects of BPA on renal epithelial cell activation, apoptosis, and DNA damage. Rhesus monkey embryo renal epithelial Marc-145 cells were exposed to 0, 10-1, 10-2, 10-3, 10-4, 10-5, and 10-6 M of BPA. Alterations in intracellular apoptosis, oxidative stress, and DNA damage were evaluated. The results showed that BPA decreased cell viability, superoxide dismutase (SOD) activity and glutathione (GSH) level, with concomitant increases in apoptosis related indices, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS) generation, thiobarbituric acid reactive substances (TBARS) content, and the rate of comet Marc-145 cells with a dose-dependent manner. The data indicated that increased oxidative stress, apoptosis and DNA damage in epithelial Marc-145 cells might play a pivotal role in the mechanism of BPA-induced nephrotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Células Epiteliais/patologia , Depuradores de Radicais Livres/toxicidade , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Animais , Sobrevivência Celular , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/embriologia , Macaca mulatta
15.
Environ Health Prev Med ; 24(1): 41, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182008

RESUMO

OBJECTIVE: Bisphenol A (BPA) is a monomer primarily used in the production of polycarbonate plastic and epoxy resins. Bisphenol F (BPF) is apparently the main BPA replacement that is used increasingly. BPF has been detected in canned food, thermal paper receipts, and soft drinks. In the present experiment, we did both in vitro and in vivo studies to evaluate the effect of low and high-dose BPF exposures on testosterone concentration, oxidative stress, and antioxidants activity in reproductive tissues of male rats. METHODS: Adult (80-90 days old) male Sprague Dawley rats (n = 36) obtained from the rodent colony of Animal Sciences Department of Quaid-i-Azam University. The direct effects of BPF on the antioxidant enzymes and testosterone secretion were measured in vitro and in vivo studies. In an in vivo experiment, adult male Sprague Dawley rats (n = 42) were exposed to different concentrations of bisphenol F (1, 5, 25, and 50 mg/kg/d) for 28 days. Various biochemical parameters were analyzed including the level of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), reactive oxygen species (ROS), and lipid peroxidation (LPO). Moreover, sperm motility, daily sperm production (DSP), comet assay, and histological analysis were performed. RESULTS: In vitro study showed that BPF exposure significantly (p < 0.05) induced oxidative stress biomarkers, i.e., ROS and LPO, while it did not change antioxidant enzyme and testicular testosterone concentration. Whereas, an in vivo study revealed that BPF induced dose-dependent effect and high-dose (100 mg/kg) exposure of BPF significantly reduced tissue protein (p < 0.05) content, CAT (p < 0.001), SOD (p < 0.05), and POD (p < 0.05) levels while significantly (p < 0.05) augmented ROS and lipid peroxidation. Furthermore, BPF reduces testosterone, LH, and FSH secretion in a dose-dependent manner. Significant (p < 0.001) reduction in plasma and intra-testicular testosterone, LH, and FSH was noticed at 100 mg/kg BFP dose. High-dose exposure reduces spermatogenesis. CONCLUSION: BPF showed an antagonistic effect on male reproductive hormones and induce alterations in testicular morphology. Increased oxidative stress and decreased testicular antioxidant status might be the underlying mechanism of BFP-induced testicular toxicity.


Assuntos
Antioxidantes/metabolismo , Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Testosterona/metabolismo , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley
16.
Sci Total Environ ; 687: 267-276, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31207516

RESUMO

The use of bisphenol A (BPA) in manufacturing of plastics is being gradually replaced by presumably safer analogues such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). Despite their widespread occurrence in the environment, there is a knowledge gap in their toxicological profiles. We investigated cytotoxic/genotoxic effects as well as changes in the expression of selected genes involved in the xenobiotic metabolism, response to oxidative stress and DNA damage upon exposure to BPs and their mixtures in human hepatocellular carcinoma HepG2 cells. BPS and BPF slightly decreased the viability of HepG2 cells, while BPAF was the most cytotoxic compound tested. BPA, BPF and BPAF induced the formation of DNA double strand breaks determined with γH2AX assay, while BPS was inactive (5-20 µg/mL). All four BPs up-regulated the expression of CYP1A1 and UGT1A1, while BPS up-regulated and BPAF down-regulated also the expression of GST1A. Only BPA up-regulated oxidative stress responsive gene GCLC, while BPAF up-regulated the expression of CDKN1A and GADD45a. At concentrations relevant for human exposure (ng/mL range) BPA and its analogues as individual compounds and in mixtures did not exert genotoxic activity, whereas BPA and BPAF as well as the mixtures up-regulated the expressions of CYP1A1 and UGT1A1.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Bioensaio , Dano ao DNA , Células Hep G2 , Humanos , Estresse Oxidativo , Sulfonas/toxicidade , Testes de Toxicidade
17.
Environ Sci Pollut Res Int ; 26(23): 23491-23504, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201698

RESUMO

This study was conducted to investigate the effects of maternal exposure to bisphenol A (BPA) on testis development of F1 male mice. The BPA exposure model of pregnant mice was prepared by intragastric administration of BPA at the doses of 0, 2.5, 5, 10, 20, and 40 mg/kg/day at gestation day (GD) 0.5-17.5. The testis index of the offspring mice was calculated at postnatal day (PND) 21 and PND 56. The results showed that maternal exposure to 20 mg/kg BPA during pregnancy significantly increased the testicular index of F1 males at PND 21, and 40 mg/kg BPA significantly decreased the testicular index of F1 males at PND 56 (P < 0.01). BPA significantly reduced serum testosterone (T) and estradiol (E2) levels, and improved testicular ERα and ERß levels in F1 males at both PND 21 and PND 56. BPA exposure also upregulated transcription of testicular Dnmt1 and inhibited the transcription of testicular Dnmt3A and Dnmt3B in F1 mice at PND 21. BPA reduced the transcriptional level of testicular DNA methyltransferase (Dnmt), increased the expression of testicular caspase-7, caspase-9, and bax, and decreased the expression of bcl-2 in F1 mice at PND 56. Consistent with that, BPA improved the apoptosis rate in the testis at PND 56 (P < 0.01 or P < 0.05). Our study indicates that BPA disrupts the secretion of testosterone, estradiol, and estrogen receptors by interfering with the transcription of testicular DNA methyltransferase (Dnmt) in offspring males, which damages testicular tissues and affects the potential reproductive function.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Testículo/crescimento & desenvolvimento , Animais , DNA (Citosina-5-)-Metiltransferases , Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Masculino , Exposição Materna , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Proteínas Proto-Oncogênicas c-bcl-2 , Receptores Estrogênicos/metabolismo , Diferenciação Sexual , Testículo/efeitos dos fármacos , Testosterona/sangue , Testes de Toxicidade
18.
Sci Total Environ ; 687: 416-422, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31212149

RESUMO

Algal cultures of Dictyosphaerium sp. were treated with a wide range (0-8 mg/L) of nonylphenol (NP) applications to investigate the species' potential to perform bioremediation of NP-contaminated wastewater and explore the mechanism of NP toxicity in algal cell. The algal species exhibited a high tolerance for NP and efficiently removed even high concentrations of NP. The accumulation of NP in algal cells tended to increase and the percentage of NP adhered to the cell walls tended to decrease as the NP concentration increased. The thylakoid density and the pyrenoid size also tended to decrease as the NP concentration rose. The key genes involved in the antioxidative pathways and photosynthetic pathways were down-regulated in the NP-treated algal cells. Algal ribosome genes were especially sensitive to NP. The results indicated that NP could induce oxidative stress in algal cells and that Dictyosphaerium sp. showed potential as a bioremediation agent.


Assuntos
Clorófitas/fisiologia , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Biodegradação Ambiental , Fotossíntese , Transcriptoma
19.
Ecotoxicol Environ Saf ; 181: 395-403, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31212188

RESUMO

The aims of this work was to investigate, in soil microcosms, the effects on soil microbial community structure and function of increasing concentrations of 4-Nonylphenol (NP). The lasts is a product of degradation of NPEOs (Nonylphenol polyethoxylates) with a known toxic and estrogenic capacity able to disrupt animal's hormonal systems. The effect of increasing concentrations of NP (0, 10, 30, 90, and 270 mg NP kg-1 of dry soil) in soil microcosms in three sampling dates (28, 56, and 112 days) over soil microbial activity and function were assessed. Soil microbial activity was estimated by microbial ATP content, and both bacterial and fungal communities composition were estimated using the terminal restriction fragment length polymorphism technique (T-RFLP). Abundance of ammonia-oxidizing bacteria (AOB) was estimated by qPCR of gene encoding for the bacterial ammonia-monoxygenase (amoA). Changes in biologically mediated soil properties were also assessed, namely water-soluble NH+4, NO-2 and NO-3 content, the two last allowing the assessment of mineralization rates. NP-spiking had some unexpected impacts on microbial community structure and functions, since (i) impacted both bacterial and fungal communities structure at the highest NP concentration tested, bacterial communities were resistant to lower concentrations, while fungal communities were increasingly impacted until the end of the incubation at day 112; (ii) no community structure resilience was observed in bacteria at the highest NP concentration nor for fungi at any concentration; (iii) microbial activity decreased with NP after 28 and 56 d, but increased in the last sampling at the highest concentrations tests, coupled to an enrichment in AOB taxa after 56 and 112 days, that at least partly explain also explain the observed speed up of nitrification rates.


Assuntos
Estrogênios não Esteroides/toxicidade , Microbiota/efeitos dos fármacos , Nitrogênio , Fenóis/toxicidade , Microbiologia do Solo , Poluentes do Solo/toxicidade , Amônia/análise , Amônia/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Fungos/genética , Fungos/isolamento & purificação , Minerais , Nitratos/análise , Nitrificação , Nitritos/análise , Solo/química
20.
Environ Pollut ; 251: 879-884, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234253

RESUMO

Genotoxic analyses are commonly used in ecotoxicological studies as early biomarkers to investigate the potential effects of environmental contaminants on biological models. Several pollutants can induce DNA damage and, therefore, counting micronuclei and other nuclear abnormalities are efficient tools to evaluate genotoxicity. Some pollutants such as 4-nonylphenol (NP), a detergent used mainly in industries, and Cyproterone Acetate (CPA), an antiandrogenic medicine, have already shown genotoxic effects on some vertebrates. However, although amphibians are considered bioindicators of environmental quality and their populations are declining worldwide, the effects of these compounds on anurans are not yet known and, therefore, we believe that it is important to investigate such effects on anurans. Since water contamination is one of the ultimate causes of amphibian decline, ecotoxicological studies are important to discuss the appropriate solutions to avoid species extinction. Thus, this study investigates the genotoxic effects on Rana catesbeiana tadpoles and juveniles after being exposed to 1, 10 and 100 µg/L NP and 0.025, 0.25 and 2.5 ng/L CPA, by counting the nuclear abnormalities after exposure. The laboratory experiments lasted 28 days. The experimental conditions were the same except for the water volume since tadpoles and juveniles exhibit different habits at different developmental stages. Compared to juveniles, tadpoles were more susceptible to both compounds as indicated by the increased nuclear abnormalities observed in the highest NP concentration and all tested CPA concentrations. The juveniles, on the other hand, responded only to the two highest CPA concentrations. We concluded that CPA, even at very low concentrations, is extremely harmful to both anuran developmental stages and, particularly, to tadpoles. The significant effects observed on tadpoles is an important outcome of this study since 100 µg/L or higher NP concentrations are frequently detected in the environment.


Assuntos
Anuros/embriologia , Acetato de Ciproterona/toxicidade , Larva/efeitos dos fármacos , Fenóis/toxicidade , Rana catesbeiana/embriologia , Poluentes Químicos da Água/toxicidade , Animais , Anuros/genética , Núcleo Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Poluição Ambiental , Larva/crescimento & desenvolvimento , Rana catesbeiana/genética
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