Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 126
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Ecotoxicol Environ Saf ; 246: 114168, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36244174

RESUMO

Black phosphorus quantum dots (BPQDs) are considered to have wide application prospects due to their excellent properties. However, there is no study on the effect of BPQDs on glucose metabolism. In this study, blood glucose was significantly increased when mice were continuously intragastrically administered 0.1 and 1 mg/kg bw BPQDs. The blood glucose level of the mice was elevated from Day 7 to Day 28. BPQD exposure also decreased the area under the curve (AUC) of the oral glucose tolerance test (OGTT). After exposure, the pancreas somatic index was increased. Moreover, the serum insulin and glucagon levels were elevated and the relative area of islet ß cells was increased in BPQD-exposed mice, while insulin signaling cascades were reduced in muscle tissues. In summary, our study demonstrated for the first time that BPQD exposure induces glucose disorder and insulin resistance in muscle, which is helpful to understand the biosafety of black phosphorus nanomaterials and promote the sustainable development of nanotechnology.


Assuntos
Resistência à Insulina , Insulinas , Pontos Quânticos , Camundongos , Animais , Pontos Quânticos/toxicidade , Fósforo , Glicemia
2.
Environ Pollut ; 311: 119986, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36007795

RESUMO

RNA N6-methyladenosine (m6A) modification regulates the cell stress response and homeostasis, but whether titanium dioxide nanoparticle (nTiO2)-induced acute pulmonary injury is associated with the m6A epitranscriptome and the underlying mechanisms remain unclear. Here, the potential association between m6A modification and the bioeffects of several engineered nanoparticles (nTiO2, nAg, nZnO, nFe2O3, and nCuO) were verified thorough in vitro experiments. nFe2O3, nZnO, and nTiO2 exposure significantly increased the global m6A level in A549 cells. Our study further revealed that nTiO2 can induce m6A-mediated acute pulmonary injury. Mechanistically, nTiO2 exposure promoted methyltransferase-like 3 (METTL3)-mediated m6A signal activation and thus mediated the inflammatory response and IL-8 release through the degeneration of anti-Mullerian hormone (AMH) and Mucin5B (MUC5B) mRNAs in a YTH m6A RNA-binding protein 2 (YTHDF2)-dependent manner. Moreover, nTiO2 exposure stabilized METTL3 protein by the lipid reactive oxygen species (ROS)-activated ERK1/2 pathway. The scavenging of ROS with ferrostatin-1 (Fer-1) alleviates the ERK1/2 activation, m6A upregulation, and the inflammatory response caused by nTiO2 both in vitro and in vivo. In conclusion, our study demonstrates that m6A is a potential intervention target for alleviating the adverse effects of nTiO2-induced acute pulmonary injury in vitro and in vivo, which has far-reaching implications for protecting human health and improving the sustainability of nanotechnology.


Assuntos
Lesão Pulmonar , Nanopartículas , Humanos , Metiltransferases , Nanopartículas/toxicidade , RNA , Espécies Reativas de Oxigênio , Titânio/toxicidade
3.
Sci Total Environ ; 846: 157504, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-35870602

RESUMO

In recent years, the widespread use of the pesticide cyprodinil has attracted attention due to its harmful effects on aquatic organisms. The purpose of this study was to evaluate the adverse effects of long-term exposure to cyprodinil on the reproductive system of female zebrafish. After the embryos had been treated with 0.1, 1 and 10 µg/L cyprodinil for 180 days, we observed that female fish treated with 1 and 10 µg/L cyprodinil showed decreased sexual attractiveness, a decreased proportion of primordial follicles in the ovary, an increased proportion of mature follicles, and increased egg production. Moreover, exposed females that mated with normal males produced offspring with increased rates of mortality and deformity (the F1 generation). In addition, the levels of gonadotropin and testosterone (T) were increased in females after cyprodinil exposure, especially in the 10 µg/L treated group. After cyprodinil treatment, some key genes in the hypothalamic-pituitary-gonad axis underwent significant changes. For example, gene expression of brain gonadotropin-releasing hormone receptors (gnrhr1, gnrhr2 and gnrhr4) was significantly downregulated after cyprodinil treatment. The study found that expression of the aromatase (cytochrome P450 family 19 subfamily A polypeptide 1a, cyp19a1a) responsible for converting T into estradiol was significantly downregulated after cyprodinil treatment, consistent with elevated T levels in the ovaries and muscles. In summary, these data provide a more comprehensive understanding of the toxicity of cyprodinil and may inform evaluation of the ecotoxicity of cyprodinil to female reproduction at environmentally relevant concentrations.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Feminino , Gônadas , Masculino , Pirimidinas , Reprodução , Vitelogeninas/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/fisiologia
4.
Toxics ; 10(6)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35736895

RESUMO

Theabrownin (TB) is a heterogeneous biomacromolecule, extracted from tea, with many functional groups. Importantly, TB possesses diverse health benefits, such as antitumor activity and blood lipid-lowering effects. Presently, the content of TB in tea extract is relatively low. Here, we obtained a deep-processed black tea extract with a high content of TB (close to 80%), which was named Herbt Tea Essences (HTE). Currently, this study was designed to evaluate the biosafety of high-content TB products on mice. We implemented acute and subacute toxic experiments to assess its safety on organs, the serum biochemical and molecular levels. In the acute exposure study, we found that the median lethal dose (LD50) value of HTE was 21.68 g/kg (21.06-24.70 g/kg, greater than 5 g/kg), suggesting that HTE had a low acute toxicity. In the 28-day subacute exposure study, our results showed that no abnormal effects were observed in the 40 and 400 mg/kg/day HTE-treated groups. However, we observed slight nephrotoxicity in the 4000 mg/kg/day HTE-treated group. The HTE-induced nephrotoxic effect might involve the inflammatory response activation mediated by the nuclear transcription factor kappa-B (NF-κB) signaling pathway. This study would provide valuable data for the TB safety assessment and promote this natural biomacromolecule application in daily drinking.

5.
Chemosphere ; 305: 135388, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35718029

RESUMO

Diuron, a widely used phenylurea herbicide, has been frequently detected in marine organism and seawater all over the world. But the understanding of potential damage of diuron on reproduction in marine fish is currently not enough. Herein, marine medaka (Oryzias melastigma) were continuously exposed to 0, 5, 50, 500, and 5000 ng/L diuron from embryo (0 dpf) to adult (180 dpf) stage. The results suggested that diuron had an adverse influence on male reproduction for marine medaka, including decreased gonado somatic index, histological changes of testes, decreased mobility of sperm, and reduced fecundity through disrupting the balance of sex hormone and genes expression related to hypothalamus-pituitary-gonadal-liver (HPGL) axis. The reduced fecundity was reflected in abnormal sexual behaviors, further inhibited growth and development of F1 embryo and larvae. Moreover, the proportion of diuron metabolites (DCPMU and DCPU) was increased in fish, but the proportion of diuron was decreased with the increasing of exposure concentration. Diuron, DCPMU, and DCPU was identified as aryl hydrocarbon receptor agonist (AhR) agonist using in silico and in vivo models. DCPMU and DCPU induced the gene expression of AhR signaling and metabolizing enzymes (such as cyp1a1) in the livers. A great deal of major metabolites affected various organs related to HPGL axis of male marine medaka and led to serious reproductive disorders. Consequently, it reveals that long-term exposure to environmentally relevant concentrations of diuron and even AhR agonist pesticides pose a potential ecological risk for marine fish.


Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Diurona/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Masculino , Oryzias/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Reprodução , Sêmen , Poluentes Químicos da Água/metabolismo
6.
Environ Pollut ; 301: 118977, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35157936

RESUMO

Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants (POPs) that have adverse effects on human health. However, the long-term health effects and potential mechanism of neonatal exposure to PCBs are still unclear. In this study, nursing male mice exposed to PCB138 at 0.5, 5, and 50 µg/kg body weight (bw) from postnatal day (PND) 3 to PND 21 exhibited increased serum uric acid levels and liver uric acid synthase activity at 210 days of age. We also found an increased kidney somatic index in the 50 µg/kg group and kidney fibrosis in the 5 and 50 µg/kg groups. Mechanistically, PCB138 induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which might have led to inflammatory responses, such as activation of the NF-κB (nuclear factor kappa-B) and NLRP3 (NOD-like receptor protein 3) pathways. The inflammatory response might regulate renal fibrosis and hypertrophy. In summary, this study reports a long-term effect of neonatal PCB exposure on uric acid metabolism and secondary nephrotoxicity and clarifies the underlying mechanism. Our work also indicates that early life pollutant exposure may be an important cause of diseases later in life.


Assuntos
Poluentes Ambientais , Hiperuricemia , Bifenilos Policlorados , Animais , Poluentes Ambientais/toxicidade , Rim , Masculino , Camundongos , Bifenilos Policlorados/toxicidade , Ácido Úrico
7.
Nanomaterials (Basel) ; 12(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35159736

RESUMO

With the increasing application of nanoparticles (NPs) in medical and consumer applications, it is necessary to ensure their safety. As m6A (N6-methyladenosine) RNA modification is one of the most prevalent RNA modifications involved in many diseases and essential biological processes, the relationship between nanoparticles and m6A RNA modification for the modulation of these events has attracted substantial research interest. However, there is limited knowledge regarding the relationship between nanoparticles and m6A RNA modification, but evidence is beginning to emerge. Therefore, a summary of these aspects from current research on nanoparticle-induced m6A RNA modification is timely and significant. In this review, we highlight the roles of m6A RNA modification in the bioimpacts of nanoparticles and thus elaborate on the mechanisms of nanoparticle-induced m6A RNA modification. We also summarize the dynamic regulation and biofunctions of m6A RNA modification. Moreover, we emphasize recent advances in the application perspective of nanoparticle-induced m6A RNA modification in medication and toxicity of nanoparticles to provide a potential method to facilitate the design of nanoparticles by deliberately tuning m6A RNA modification.

8.
Aquat Toxicol ; 244: 106106, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35131552

RESUMO

Diuron is one of the most widely used herbicides worldwide. It has been widely detected in various aquatic environments, especially in marine ecosystems. Although direct effects of diuron exposure on various organisms have been reported, little is known about its effects on marine fishes including multigenerational effects. Herein, the filial generation (F1) of diuron-exposed marine medaka (Oryzias melastigma) (F0) was raised in clean seawater from fertilized eggs to adulthood and used as a marine fish model to study the potential multigenerational effects of diuron. We found that the successful hatching of F1 larvae was significantly reduced and that ovarian development in F1 females was retarded. A significant increase in the percentage of previtellogenic oocytes, along with a visual decrease in the percentage of vitellogenic and mature oocytes in the F1 ovary, were observed. The hormone levels of the hypothalamus-pituitary-gonad-liver axis and vitellogenin-related transcription were downregulated. In addition, the mRNA levels of DNA methyltransferase in the brain, ovary and liver of F1 adult fish exhibited significant upregulation, suggesting that the probable underlying multigenerational mechanism might be associated with epigenetic modifications. Taken together, these results demonstrated that chronic environmental diuron exposure in F0 marine medaka can inhibit F1 ovary development and suggested that diuron may affect marine fish thriving in the ocean.


Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Diurona , Ecossistema , Feminino , Ovário/química , Poluentes Químicos da Água/toxicidade
9.
Theranostics ; 12(2): 782-795, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976213

RESUMO

Rationale: Polycystic ovary syndrome (PCOS) is closely linked to follicular dysplasia and impaired bidirectional oocyte-granulosa cell (GC) communication. Given that PCOS is a heterogeneous, multifactorial endocrine disorder, it is important to clarify the pathophysiology of this ovarian disease and identify a specific treatment. Methods: We generated PCOS rat models based on neonatal tributyltin (TBT) exposure and studied the therapeutic effect and mechanism of resveratrol (RSV), a natural plant polyphenol. Transcriptome analysis was conducted to screen the significantly changed pathways, and a series of experiments, such as quantitative real-time polymerase chain reaction (PCR), Western blot and phalloidin staining, were performed in rat ovaries. We also observed similar changes in human PCOS samples using Gene Expression Omnibus (GEO) database analysis and quantitative real-time PCR. Results: We first found that injury to transzonal projections (TZPs), which are specialized filopodia that mediate oocyte-GC communication in follicles, may play an important role in the etiology of PCOS. We successfully established PCOS rat models using TBT and found that overexpressed calcium-/calmodulin-dependent protein kinase II beta (CaMKIIß) inhibited TZP assembly. In addition, TZP disruption and CAMK2B upregulation were also observed in samples from PCOS patients. Moreover, we demonstrated that RSV potently ameliorated ovarian failure and estrus cycle disorder through TZP recovery via increased cytoplasmic calcium levels and excessive phosphorylation of CaMKIIß. Conclusions: Our data indicated that upregulation of CaMKIIß may play a critical role in regulating TZP assembly and may be involved in the pathogenesis of PCOS associated with ovarian dysfunction. Investigation of TZPs and RSV as potent CaMKIIß activators provides new insight and a therapeutic target for PCOS, which is helpful for improving female reproduction.


Assuntos
Comunicação Celular/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Pseudópodes/efeitos dos fármacos , Resveratrol/uso terapêutico , Adulto , Animais , Apoptose/efeitos dos fármacos , Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/metabolismo , Modelos Animais de Doenças , Feminino , Células da Granulosa/metabolismo , Humanos , Oócitos/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Pseudópodes/metabolismo , Ratos , Ratos Sprague-Dawley , Compostos de Trialquitina
10.
Environ Sci Pollut Res Int ; 29(20): 30537-30547, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35000155

RESUMO

Propylene glycol (PG) is widely used in the foods, pharmaceuticals, oil industry, animal feed, cosmetics and other industries. Because of the existence of a chiral carbon center, PG forms R (Rectus)- and S (Sinister)-enantiomers. Currently, the toxicity study of its R-, S-enantiomers is still very scarce. In this study, we have assessed the developmental toxicity and neurotoxicity of the R-, S-, and RS-PG enantiomers in zebrafish larvae. We found that exposure to R-, S-, and RS-PG enantiomers did not significantly affect the basic developmental endpoints of embryos or larvae (i.e., embryonic movement, hatching, mortality, malformation, heartbeat, body length), indicating that R-, S-, and RS-PG exposures did not exhibit the basic developmental toxicity in zebrafish larvae. The toxicity of three enantiomers was lower than that of ethanol, and there was no significant difference between them. However, R-, S-, and RS-PG exposures with high doses could significantly change the eye diameter and locomotor activity of larval zebrafish, indicating that R-, S-, and RS-PG enantiomers of high doses could potentially exhibit the neurotoxicity and ocular developmental toxicity in zebrafish larvae. Therefore, the potential neurotoxicity and ocular developmental toxicity of R-, S-, and RS-PG enantiomers for infants and toddlers should be considered.


Assuntos
Síndromes Neurotóxicas , Poluentes Químicos da Água , Animais , Embrião não Mamífero , Humanos , Larva , Propilenoglicol , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
11.
Life Sci ; 288: 120205, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34871665

RESUMO

AIMS: This study was aimed to explore whether sacran polysaccharide has a therapeutic effect on atopic dermatitis (AD) and its possible mechanisms. MATERIALS AND METHODS: 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice were treated with 0.2% Sacran, 0.5% Sacran and 0.1% tacrolimus. Through scoring dermatitis severity, measuring ear thickness, cracking behavior, open field test, we evaluated the therapeutic effect of Sacran on DNCB-induced AD mice. CD4+ T cells and CD8+ T cells were evaluated by flow cytometry. The relative expression of Ifng and Il4 were measured by real-time quantitative PCR. KEY FINDINGS: Sacran could relieved the symptoms of DNCB-induced AD mice, such as AD score, ear thickness, and IgE release. Sacran may alleviate dermatitis by inhibiting Th2 activation and reducing IgE release. SIGNIFICANCE: Our research further proved that polysaccharide Sacran has anti-dermatitis effects, and also clarified its mechanism of alleviating dermatitis by inhibiting the activation of Th2 cells and reducing the release of IgE, which provides a theoretical basis for the future clinical transformation of polysaccharide Sacran.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno/toxicidade , Imunoglobulina E/metabolismo , Inflamação/prevenção & controle , Polissacarídeos/farmacologia , Células Th2/imunologia , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Feminino , Indicadores e Reagentes/toxicidade , Inflamação/etiologia , Camundongos , Camundongos Endogâmicos BALB C , Células Th2/efeitos dos fármacos
12.
Small Methods ; 5(3): e2001045, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-34927824

RESUMO

Nanosafety is a major concern for nanotechnology development. Evaluation of the transcriptome and the DNA methylome is proposed for nanosafety assessments. RNA m6A modification plays a crucial role in development, disease, and cell fate determination through regulating RNA stability and decay. Here, since black phosphorus quantum dots (BPQDs), among many other types of QDs, increase the global m6A level and decrease the demethylase ALKBH5 level in lung cells, the epitranscriptome is taken into consideration for the first time to evaluate nanosafety. Both the transcriptome and m6A epitranscriptome analyses show that BPQDs alter many biological processes, such as the response to selenium ions and the lipoxygenase pathway, indicating possible ferroptosis activation. The results further show that BPQDs cause lipid peroxidation, mitochondrial dysfunction, and iron overload. Recognition of these modified mRNAs by YTHDF2 leads to mRNAs' decay and eventually ferroptosis. This study shows that RNA m6A modification not only is a more sophisticated indicator for nanosafety assessment but also provides novel insight into the role of RNA m6A in regulating BPQD-induced ferroptosis, which may be broadly applicable to understanding the functions of RNA m6A under stress.


Assuntos
Ferroptose , Pontos Quânticos , Ferroptose/genética , Fósforo/metabolismo , Pontos Quânticos/toxicidade , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética
13.
Aquat Toxicol ; 241: 106002, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34717145

RESUMO

Cyprodinil, one of the main pyrimidinamine fungicides, has been used to control fungal diseases in plants and vegetables worldwide. Previous studies have investigated the influences of cyprodinil on the developmental and reproductive toxicity of fish. However, it remains unknown whether it affects fish behaviors and the underlying mechanisms. In our current study, zebrafish, an ideal model animal for behavioral studies, were exposed to cyprodinil from fertilization to 240 days postfertilization at 0.1 µg/L (environmentally relevant concentration) and 1, 10 µg/L. Firstly, we observed that aggressive behavior of zebrafish was significantly enhanced after exposure to 0.1-10 µg/L cyprodinil and antipredator behavior was decreased after exposure. Cyprodinil exposure altered the adrenocorticotropic hormone and cortisol levels, which regulate cortisol homeostasis and were significantly reduced in all exposure groups (0.1-10 µg/L). In addition, most of the key genes in the hypothalamic-pituitary-interrenal gland axis, such as corticotropin-releasing hormone and melanocortin 2 receptor, were downregulated significantly in all exposure groups, which was consistent with the hormone levels. In addition, in the hypothalamus, the number of apoptotic cells increased in a dose-dependent manner in the cyprodinil exposure groups. Moreover, these changes were potentially responsible for the increased aggression of zebrafish during the mirror-like aggressive test and for the reduced antipredator behavior during the predator avoidance test. Overall, the data provided herein further our understanding of cyprodinil toxicity and can be used to assess the ecological effects of cyprodinil on the induction of abnormal behaviors at the environmental level.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Agressão , Animais , Hidrocortisona , Pirimidinas , Poluentes Químicos da Água/toxicidade
14.
Aquat Toxicol ; 238: 105917, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34333370

RESUMO

Diuron, a commonly used herbicide and antifouling biocide, has been frequently detected in seawater. The effects of diuron on fish behaviour are currently poorly understood. Herein, the marine medaka (Oryzias melastigma) was continuously exposed to environmentally realistic levels of diuron from the fertilised egg stage to the adult stage. Behavioural evaluation of adult marine medaka indicated that exposure to diuron increased anxiety in the light-dark test and increased predator avoidance. In addition, diuron exposure significantly reduced aggression, social interaction, shoaling, and learning and memory ability. However, only negligible variations in foraging behaviour and in behaviour in the novel tank test were observed. Marine medaka chronically exposed to diuron also showed decreased levels of dopamine in the brain, and changes were observed in the transcription of genes related to dopamine synthesis, degradation and receptors. Exposure to 5000 ng/L diuron caused significant downregulation of the expression of the genes of tyrosine hydroxylase and monoamine oxidase and significantly upregulated the expression of the genes of the D5 dopaminergic receptor. The relative expression of the D4 dopaminergic receptor was significantly upregulated in the 50, 500 and 5000 ng/L diuron-treated groups. These findings highlight the significant neurotoxic effects of diuron and the extent to which this may involve the dopaminergic system of the brain. More broadly, this study reveals the ecological risk associated with environmentally realistic levels of diuron in marine animals.

15.
Environ Pollut ; 283: 117028, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33892371

RESUMO

As ubiquitous, persistent organic pollutants, polycyclic aromatic hydrocarbons (PAHs) have adverse impacts on human health. Phenanthrene (Phe) is one of the most abundant PAHs in the environment. However, the long-term effects of exposure to environmental level of Phe on the kidneys and the potential mechanisms are unclear. T helper (Th) cells, a subtype of CD4+ T cells that play a central role in the renal immune microenvironment. In this study, male mice were chronically exposed to 5, 50, and 500 ng/kg bw Phe every other day for total 210 days. Those results indicated that environmental Phe exposure caused kidney hypertrophy, injury and fibrosis in the mice. Chronic, long-term environmental level of Phe exposure did not significantly alter the innate immune response but induced adaptive immune response changes (Th1/Th2 related cytokines release), causing a type 1 immune response in the 5 ng/kg bw Phe group and a type 2 immune response in the high dose groups (50 and 500 ng/kg bw). This study provides novel insights into the roles of adaptive immune response in long-term PAH exposure-induced chronic kidney injury and fibrosis, which is beneficial for further understanding the potential health hazards of PAHs and providing new avenues for immune intervention strategies to alleviate PAHs toxicity.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Imunidade Adaptativa , Animais , Fibrose , Rim , Masculino , Camundongos , Fenantrenos/toxicidade
16.
Environ Toxicol ; 36(4): 665-674, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33258555

RESUMO

Numerous studies have shown that endocrine-disrupting chemicals are one of the important pathogenic factors in women with polycystic ovary syndrome. Our previous study has revealed that bisphenol A (BPA) can cause steroid hormone imbalance, polycystic ovary, and estrus cycle disorder. In this study, we aimed to explore the effect of BPA, a typical environmental estrogen, on the synthesis of steroid hormones in human ovarian granulosa KGN cells. Exposure of KGN cells to BPA (0.5, 5, 50, and 500 µg/L) resulted in the decrease of progesterone (P), estradiol (E2), and the ratio of estradiol to testosterone (E2/T). BPA affected the expression of genes related to steroid hormone synthesis in KGN cells, including the decreased expression of the steroidogenic acute regulatory protein, ferredoxin, and ferredoxin reductase genes during progesterone synthesis; upregulating the expression of cytochrome p450 oxidoreductase gene associated with E2 and T synthesis; and the downregulated cytochrome P450 family 1 subfamily A member 1 and cytochrome P450 family 1 subfamily B member 1 in E2 degradation. BPA also reduced the expression of stimulatory G proteins (GS) in follicle-stimulating hormone receptor (FSHR)/GS/adenylate cyclase (AC) signaling pathway. In summary, our research has demonstrated that environment-relevant level of BPA exposure leads to steroid hormone synthesis disorder in human ovarian granulosa cells, which might cause the reduction of gene expression in hormone synthesis and the suppression of the FSHR/GS/AC signaling pathway.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Estradiol/biossíntese , Células da Granulosa/efeitos dos fármacos , Fenóis/toxicidade , Progesterona/biossíntese , Testosterona/biossíntese , Animais , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Regulação para Cima
17.
Chemosphere ; 265: 129099, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33272675

RESUMO

The aryl hydrocarbon receptor (AhR), which is a ligand-dependent transcription factor, plays a crucial role in the regulation of xenobiotic metabolism. There are a large number of artificial or natural molecules in the environment that can activate AhR. In this study, we developed a virtual screening procedure to identify potential ligands of AhR. One structure-based method and two ligand-based methods were used for the virtual screening procedure. The results showed that the precision rate (0.96) and recall rate (0.64) of our procedure were significantly higher than those of a procedure used in a previous study, which suggests that supervised machine learning techniques can greatly improve the performance of virtual screening. Moreover, a pesticide dataset including 777 frequently used pesticides was screened. Seventy-seven pesticides were identified as potential AhR ligands by all three screening methods, among which 12 have never been previously reported as AhR agonists. Two non-agonist AhR ligands and 14 of the 77 pesticides were randomly selected for testing by in vitro and in vivo assays. All 14 pesticides showed different degrees of AhR agonistic activity, and none of the two non-agonist AhR ligand pesticides showed AhR agonistic activity, which suggests that our procedure had good robustness. Four of the pesticides were reported as AhR agonists for the first time, suggesting that these pesticides may need further toxicity assessment. In general, our procedure is a rapid, powerful and computationally inexpensive tool for predicting chemicals with AhR agonistic activity, which could be useful for environmental risk prediction and management.


Assuntos
Praguicidas , Receptores de Hidrocarboneto Arílico , Ligantes , Aprendizado de Máquina Supervisionado
18.
J Environ Sci (China) ; 100: 240-249, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33279036

RESUMO

Quantum dots (QDs) are new types of nanomaterials. Few studies have focused on the effect of different surface modified QDs on embryonic development. Herein, we compared the in vivo toxicity of CdSe/ZnS QDs with carboxyl (-COOH) and amino (-NH2) modification using zebrafish embryos. After exposure, the two CdSe/ZnS QDs decreased the survival rate, hatching rate, and embryo movement of zebrafish. Moreover, we found QDs attached to the embryo membrane before hatching and the eyes, yolk and heart after hatching. The attached amount of carboxyl QDs was more. Consistently, the Cd content in embryos and larvae was higher in carboxyl QD-treatment. We further observed that the two QDs caused zebrafish pericardial edema and cardiac dysfunction. In line with it, both carboxyl and amino QDs up-regulated the transcription levels of cardiac development-related genes, and the levels were higher in carboxyl QD-treated groups. Furthermore, the chelator of Cd2+ diethylene triamine pentacetate acid could partially rescued the developmental toxicity caused by the two types of QDs suggesting that both the nature of QDs and the release of Cd2+ contribute to the developmental toxicity. In conclusion, the two CdSe/ZnS QDs have developmental toxicity and affect the cardiac development, and the carboxyl QDs is more toxic possibly due to the higher affinity and more release to embryos and larvae. Our study provides new knowledge that the surface functional modification of QDs is critical on the development on aquatic species, which is beneficial to develop and applicate QDs more safely and environment-friendly.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Compostos de Selênio , Animais , Compostos de Cádmio/toxicidade , Pontos Quânticos/toxicidade , Compostos de Selênio/toxicidade , Sulfetos/toxicidade , Peixe-Zebra , Compostos de Zinco/toxicidade
19.
J Hazard Mater ; 402: 122875, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33254732

RESUMO

Black phosphorus quantum dots (BP-QDs) are a new type of zero-dimensional (0D) nanomaterial that has been widely used due of their superior properties in many biomedical fields, but limited studies have focused on the biocompatibility of BP-QDs, particularly in the respiratory system. In this study, we investigated the potential lung cell toxicity of BP-QDs in vitro. Two human lung-derived cells, A549 and Beas-2B, were treated with 5∼20 µg/mL BP-QDs for 24 h. The results showed that BP-QDs triggered significant lung cell toxicity, including a dose-dependent decrease in cell viability, lactate dehydrogenase (LDH) leakage, cell shape changes, cellular oxidative stress and cell cycle arrest. In addition, pretreatment with the classical phagocytosis inhibitor cytochalasin D (Cyto D) alleviated the decrease in cell viability and LDH leakage induced by BP-QDs. In contrast, BP-QDs induced the production of cellular reactive oxygen species (ROS) and decreases in the glutathione level, whereas the ROS scavenger N-acetyl-L-cysteine (NAC) could protect A549 and Beas-2B cells from BP-QD-induced cellular oxidative stress. Taken together, the results from this study indicate that the potential toxic effects and mechanisms of BP-QDs in two different human lung cells should be considered to evaluate the lung cell safety of BP-QDs.


Assuntos
Fósforo , Pontos Quânticos , Sobrevivência Celular , Humanos , Pulmão , Fósforo/toxicidade , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio
20.
Environ Pollut ; 290: 118050, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461418

RESUMO

Propylene glycol (PG; 1,2-propanediol) has been commonly used as a food additive and vehicle in pharmaceutical preparations. PG can form rectus (R-) enantiomers and sinister (S-) enantiomers. Herein, Kunming mice were used as the animal model to evaluate the acute and subacute oral toxicity of R-PG, S-PG and RS-PG (1:1 racemic mixture of R-PG and S-PG). The median lethal doses of R-PG, S-PG and RS-PG administered by oral gavage to mice were 22.81 g/kg, 26.62 g/kg and 24.92 g/kg, respectively. In the 28-day oral subacute toxicity study, the body weight, organ weights, serum biochemical, and renal histology were examined. There was no difference in subacute toxicity among R-PG, S-PG and RS-PG. The administration of 1 and 5 g/kg/day PG for 28 days caused nephrotoxicity. The kidney somatic index and levels of blood urea nitrogen exhibited a significant increase. Moreover, the activities of superoxide dismutase, catalase, and glutathione peroxidase significantly decreased after the treatment with PG. The levels of malondialdehyde, tumor necrosis factor α, interleukin 1ß, and interleukin 6 significantly increased in the kidney. The results show that the nephrotoxic effects of PG are induced by oxidative stress, and the activation of the inflammatory response is mediated by the NF-κB signaling pathway. Together, these findings provide information on R-PG, S-PG and RS-PG treatments for the risk assessment of toxicity and effects on human health.


Assuntos
Estresse Oxidativo , Propilenoglicol , Animais , Catalase/metabolismo , Rim/metabolismo , Malondialdeído/metabolismo , Camundongos , Propilenoglicol/metabolismo , Propilenoglicol/toxicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...