Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.207
Filtrar
1.
Ecotoxicol Environ Saf ; 208: 111543, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396091

RESUMEN

Acrylamide (ACR) is generated during thermal processing of carbohydrate-rich foods at high temperature and can directly enter the body through ingestion, inhalation and skin contact. The toxicity of ACR has been widely studied. The main results of these studies show that exposure to ACR can cause neurotoxicity in both animals and humans, and show reproductive toxicity and carcinogenicity in rodent animal models. However, the mechanism of toxicity of ACR has not been studied by metabolomics approaches, and the effect of ACR on autophagy remains unknown. Here, U2OS cell were treated with ACR 6 and 24 h and collected for further study. We have demonstrated that ACR inhibited autophagic flux, and increased ROS content. Accumulation of ROS resulted in increase of apoptosis rates and secretion of inflammatory factors. In addition, significant differences in metabolic profiles were observed between ACR treated and control cells according to multiple analysis models. A total of 73 key differential metabolites were identified. They were involved in multiple metabolic pathways. Among them, exposure to ACR caused glycolysis/gluconeogenesis attenuation by decreasing levels of glycolytic intermediates, reduced the rate of the TCA cycle, while elevating levels of several amino acid metabolites and lipid metabolites. In summary, our study provides useful evidence of cytotoxicity caused by ACR via metabolomics and multiple bioanalytic methods.


Asunto(s)
Acrilamida/toxicidad , Sustancias Peligrosas/toxicidad , Metaboloma , Metabolómica , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos
2.
Ecotoxicol Environ Saf ; 208: 111730, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396061

RESUMEN

Copper (Cu) is a common environmental pollutant in nature. Cu-poisoning can cause liver damage and erythrocytes hemolysis. To evaluate the effect of CuSO4 poisoning on the morphological and functional characteristics of goat red blood cells. Five 10-14-month-old goats were selected for jugular vein blood sampling to obtain erythrocytes, and then the erythrocytes were processed with different concentrations (0, 10, 20, 30, 40 and 50 µmol/L) of CuSO4 for 48 h, and 40 µmol/L doses CuSO4 incubated for different time (12, 24, 36, 48 and 60 h) to process erythrocytes. We observed the changes in erythrocyte morphology through scanning electron microscopy, and detected the antioxidant function and activities of three ATPases. Additionally, biological properties were examined from the perspectives of phospholipids and membrane protein components, permeability fragility, and fluidity in erythrocytes. We found that after CuSO4 treatment, the antioxidant capacity of erythrocytes decreased, which was manifested as increased MDA content and decreased CuZn-SOD and GSH-Px activities (p < 0.05). In addition, we also found that erythrocyte fluidity decreased, osmotic fragility increased, membrane phospholipid percentage and protein composition changes abnormally, and Na+/K+-ATPase, Mg2+-ATPase and Ca2+-ATPase activities decreased (p < 0.05). From the results, it can be concluded that CuSO4 exposure causes hemolysis of goat erythrocytes through oxidative stress to the structure and function of erythrocytes, showing a dose-time effect.


Asunto(s)
Sulfato de Cobre/toxicidad , Sustancias Peligrosas/toxicidad , Adenosina Trifosfatasas/metabolismo , Animales , Antioxidantes/metabolismo , Cobre/análisis , Membrana Eritrocítica/química , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/metabolismo , Eritrocitos/efectos de los fármacos , Cabras/metabolismo , Hemólisis/efectos de los fármacos , Fragilidad Osmótica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosfolípidos/análisis , Pruebas de Toxicidad
3.
Ecotoxicol Environ Saf ; 208: 111731, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396062

RESUMEN

Cadmium (Cd) is an environmental toxicant and a nonessential metal. Cd can attack a wide range of organs, such as the liver, kidney, lung, ovary, testis, brain, and muscle in vertebrates. Among these organs, the testis might be the most sensitive organ to Cd toxicity. Metallothionein (MT) is a cysteine-rich protein with a low molecular weight, that can bind with Cd and eliminate reactive oxygen species (ROSs). Hydrogen peroxide, which as a crucial type of ROS that is induced by Cd, can be eliminated by catalase (CAT) in the self-protection of cells and to realize Cd toxicity resistance. To investigate the functions of MT and CAT in the testis of Cynops orientalis, we cloned the full-length MT and CAT genes of C. orientalis for the first time. Immunofluorescence results demonstrated that MT and CAT were expressed in Sertoli cells and all spermatogenic cells in the testis of C. orientalis. The results of the ultrastructural damage assay demonstrated that there were various impairments, which included organelle vacuolization, abnormal chromatin distribution, and apoptotic bodies, in somatic cells that were exposed to Cd. However, the anomalies of spermatozoa were located mainly in the mid-piece and head, many of which showed severely impaired structures. The results demonstrated that MT and CAT expression had distinct patterns in response to various Cd concentrations: an increase in MT mRNA levels with elevated Cd levels and a persistent increase in CAT mRNA levels with elevated Cd levels. These results suggested that MT and CAT play roles in Cd toxicity resistance in the testis and that the expression of CAT may be a better biomarker than the expression of MT for assessing Cd pollution.


Asunto(s)
Cadmio/toxicidad , Catalasa/metabolismo , Clonación Molecular , Sustancias Peligrosas/toxicidad , Metalotioneína/metabolismo , Salamandridae/fisiología , Testículo/efectos de los fármacos , Animales , Secuencia de Bases , Humanos , Hígado/metabolismo , Masculino , ARN Mensajero/metabolismo , Salamandridae/genética , Salamandridae/metabolismo , Células de Sertoli/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo
4.
Ecotoxicol Environ Saf ; 208: 111629, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396149

RESUMEN

As an alternative to volatile organic solvents, ionic liquids (ILs) are known as "green solvents", and widely used in industrial applications. However, due to their high solubility and stability, ILs have tendency to persist in the water environment, thus having potential negative impacts on the aquatic ecosystem. For assessing the environmental risks of ILs, a fundamental understanding of the toxic effects and mechanisms of ILs is needed. Here we evaluated the cytotoxicity of 1-methyl-3-decylimidazolium chloride ([C10mim]Cl) and elucidated the main toxic mechanism of [C10mim]Cl in human cervical carcinoma (Hela) cells. Microstructural analysis revealed that [C10mim]Cl exposure caused the cell membrane breakage, swollen and vacuolated mitochondria, and spherical cytoskeletal structure. Cytotoxicity assays found that [C10mim]Cl exposure increased ROS production, decreased mitochondrial membrane potential, induced cell apoptosis and cell cycle arrest. These results indicated that [C10mim]Cl could induce damage to cellular membrane structure, affect the integrity of cell ultrastructure, cause the oxidative damage and ultimately lead to the inhibition of cell proliferation. Moreover, alterations of biochemical information including the increased ratios of unsaturated fatty acid and carbonyl groups to lipid, and lipid to protein, and the decreased ratios of Amide I to Amide II, and α-helix to ß-sheet were observed in [C10mim]Cl treated cells, suggesting that [C10mim]Cl could affect the structure of membrane lipid alkyl chain and cell membrane fluidity, promote the lipid peroxidation and alter the protein secondary structure. The findings from this work demonstrated that membrane structure is the key target, and membrane damage is involved in [C10mim]Cl induced cytotoxicity.


Asunto(s)
Sustancias Peligrosas/toxicidad , Líquidos Iónicos/toxicidad , Membrana Celular/efectos de los fármacos , Ecosistema , Células HeLa , Humanos , Imidazolinas/toxicidad , Mitocondrias , Estructura Secundaria de Proteína , Solventes
5.
Chemosphere ; 263: 128017, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32841881

RESUMEN

Phthalic acid esters (PAEs), as typical hormone pollutants, do harms to human health after enrichment over a long term exposure, causing the loss of oxygen-carrying function of red blood cells (RBCs). This study has investigated the mechanism for the toxicity of dimethyl phthalate (DMP) on the oxygen-carrying function of RBCs by measuring the iron release content of hemoglobin (Hb) in vivo and in vitro. The hematologic examination showed that the high dose of DMP at 1000 mg/kg significantly reduced the Hb content and increased the granulocyte content, whereas such toxicity was not relatively observed at a low (50 mg/kg) or a medium (250 mg/kg) dose of DMP. The in vitro experiments showed that DMP, incubated with RBCs, increased the iron release content as a function of DMP concentration. Interestingly, such a phenomenon was not observed when DMP was incubated with Hb alone, indicating that the release of hemoglobin iron could not directly caused by the combination of DMP and hemoglobin. The in vivo experiments indicated that DMP induced iron release and oxidative stress for rat RBCs. Moreover, vitamin C and E was found to reduce the level of iron release by recovering erythrocytes from the oxidative stress induced by DMP. This work has revealed that the oxidative stress induced by DMP, causing the release of Hb iron from RBCs, is the reason for the toxicity of DMP to the oxygen-carrying function.


Asunto(s)
Sustancias Peligrosas/toxicidad , Ácidos Ftálicos/toxicidad , Animales , Contaminantes Ambientales , Eritrocitos , Hemoglobinas , Humanos , Hierro , Estrés Oxidativo , Oxígeno , Ratas
6.
Chemosphere ; 263: 127990, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32846288

RESUMEN

The clinical manifestations of methylmercury toxicity do not differ greatly according to the acute and/or chronic methylmercury overexposure.


Asunto(s)
Exposición a Riesgos Ambientales/estadística & datos numéricos , Sustancias Peligrosas/toxicidad , Mercurio/toxicidad , Animales , Humanos , Mamíferos , Mercurio/análisis , Compuestos de Metilmercurio/toxicidad
7.
Ecotoxicol Environ Saf ; 207: 111257, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32890951

RESUMEN

Cadmium has been widely detected in the environment and various foods. The association between cadmium burden and osteoporosis has been studied in cohorts. However, the effects and mechanisms of environmental cadmium exposure on bone metabolism is poorly understood. This study aims to investigate the altered metabolites in bone cells affected by low-level cadmium by metabolomics analysis. Specifically, we used the dosage of cadmium that do not decrease the cell viability (determined by MTT assay) to treat Saos-2 cells for 24 h. ICP-MS was applied to quantify the cadmium in culture medium and cell precipitate. The cellular metabolites were extracted and analyzed by liquid chromatography-mass spectrometry. The pathway analysis based on the identified differential metabolites showed that 1 µM cadmium significantly affected citric acid cycle and malate-aspartate shuttle, while 10 µM cadmium treatment affected citric acid cycle, alanine metabolism, glucose-alanine cycle, pyrimidine metabolism and glutamate metabolism. Taken together, 1 µM cadmium exposure could suppress the electrons transportation from the cytosol to mitochondrial matrix in Saos-2, and the impediment of the electron transport chain further inhibited downstream activities in citric acid cycle, which resulted in the accumulation of pyruvic acid. In addition, the suppressed pyrimidine degradation resulted in senescent nucleic acid accumulation and the decrease of mRNA transcription in Saos-2 cells. In general, our studies unveil the cadmium-induced metabolic perturbations in Saos-2 cells and demonstrate the feasibility of our established metabolomics pipeline to understand cadmium-induced effects on bone.


Asunto(s)
Cadmio/toxicidad , Sustancias Peligrosas/toxicidad , Cadmio/metabolismo , Supervivencia Celular/efectos de los fármacos , Cromatografía Liquida , Exposición a Riesgos Ambientales , Humanos , Espectrometría de Masas , Metabolómica/métodos , Mitocondrias/metabolismo , Osteoblastos/efectos de los fármacos , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos
8.
Ecotoxicol Environ Saf ; 207: 111231, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32916527

RESUMEN

Lead, a common metallic contaminant, is widespread in the living environment, and has deleterious effects on the reproductive systems of humans and animals. Although numerous toxic effects of lead have been reported, the effects and underlying mechanisms of the impacts of lead exposure on the female reproductive system, especially oocyte maturation and fertility, remain unknown. In this study, mice were treated by gavage for seven days to evaluate the reproductive damage and role of Nrf2-mediated defense responses during lead exposure. Lead exposure significantly reduced the maturation and fertilization of oocytes in vivo. Additionally, lead exposure triggered oxidative stress with a decreased glutathione level, increased amount of reactive oxygen species, and abnormal mitochondrial distribution. Moreover, lead exposure caused histopathological and ultrastructural changes in oocytes and ovaries, along with decreases in the activities of catalase, glutathione peroxidase, total superoxide dismutase, and glutathione-S transferase, and increases in the levels of malonaldehyde in mouse ovaries. Further experiments demonstrated that lead exposure activated the Nrf2 signaling pathway to protect oocytes against oxidative stress by enhancing the transcription levels of antioxidant enzymes. In conclusion, our study demonstrates that lead activates the Nrf2/Keap1 pathway and impairs oocyte maturation and fertilization by inducing oxidative stress, leading to a decrease in the fertility of female mice.


Asunto(s)
Sustancias Peligrosas/toxicidad , Plomo/toxicidad , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Plomo/metabolismo , Malondialdehído/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Oocitos/efectos de los fármacos , Oogénesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo
9.
Ecotoxicol Environ Saf ; 207: 111262, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32916531

RESUMEN

Mercury (Hg) in its all forms, including inorganic Hg (iHg) is an environmental contaminant due to toxicity and diseases in human. However, a little is known about the underlying mechanisms responsible for iHg toxicity. Selenium (Se) is an essential trace element, recognized as an antioxidant and protective agent against metal toxicities. The purpose of this research was to investigate ameliorations of Se counter to iHg-mediated toxicity in PC12 cells. Cytotoxic assays have been shown that iHg (5 µM) caused oxidative stress and intrinsic apoptosis via ROS generation, oxidizing glutathione, damaging DNA, degrading cell membrane integrity, down-regulating mTOR, p-mTOR, akt and ERK1, and up-regulating cleaved caspase 3 and cytochrome c release in PC12 cells 48 h after incubation. Co-treatment of Se (5 µM) inhibited intrinsic apoptosis and oxidative stress induced by iHg (5 µM) via inhibiting ROS formation, boosting GPx contents, increasing reduced glutathione, limiting DNA degradation, improving cell membrane integrity, up-regulating mTOR, p-mTOR, akt, ERK1 and caspase 3, and down-regulating cleaved caspase 3 and cytochrome c leakage in PC12 cells. In conclusion, these results recommended that excessive ROS generation acts a critical role in iHg-influenced oxidative stress and co-treatment of Se attenuates iHg-cytotoxicity through its antioxidant properties.


Asunto(s)
Sustancias Peligrosas/toxicidad , Mercurio/toxicidad , Sustancias Protectoras/farmacología , Selenio/farmacología , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Caspasa 3 , Citocromos c/metabolismo , Glutatión/metabolismo , Humanos , Mercurio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Ratas , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR
10.
Ecotoxicol Environ Saf ; 207: 111272, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32927162

RESUMEN

Tobacco smoke is a common global environmental pollutant. Maternal tobacco smoke/nicotine exposure has long-term toxic effects on immune organs. We previously found that prenatal nicotine exposure (PNE)-induced programmed immune diseases caused by fetal thymic hypoplasia, but the mechanism still unknown. Autophagy has important functions in maintaining thymopoiesis, whether autophagy was involved in PNE-inhibited fetal thymocytes development is also obscure. Therefore, this study aimed to investigate how nicotine changed the development of fetal thymocytes from the perspective of autophagy in vivo and in vitro. PNE model was established by 3 mg/kg nicotine administration in Balb/c mice from gestational day 9 to 18. The results showed that PNE reduced the percentage and absolute number of CD69-CD4+SP cells, suggesting a block of fetal thymocytes mature. PNE promoted autophagosome formation, autophagy related proteins (Beclin1, LC3I/II) expression, and upregulated α7 nAChR as well as AMPK phosphorylation in fetal thymus. Moreover, PNE promoted Bcl10 degradation via autophagy-mediated proteolysis and inhibited p65 activation, blocking the transition of thymocytes between the DP to SP stage. Further, primary thymocytes were treated with nicotine in vitro and showed induced autophagy in a dose- and time-dependent manner. In addition, nicotine-inhibited CD69-CD4+SP cells and the Bcl10/p-p65 pathway have been reversed by an autophagy inhibitor. The α7 nAChR specific antagonist abrogated nicotine-induced AMPK phosphorylation and autophagy initiation. In conclusion, our findings showed that PNE repressed the Bcl10/p-p65 development pathway of CD4+SP cells by triggering autophagy, and illuminated the developmental origin mechanism of programmed immune diseases in PNE offspring.


Asunto(s)
Sustancias Peligrosas/toxicidad , Nicotina/toxicidad , Timocitos/fisiología , Animales , Autofagia/efectos de los fármacos , Proteína 10 de la LLC-Linfoma de Células B , Beclina-1 , Femenino , Feto , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Embarazo , Efectos Tardíos de la Exposición Prenatal , Timocitos/efectos de los fármacos , Timocitos/inmunología , Vitaminas
11.
Ecotoxicol Environ Saf ; 209: 111759, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33341695

RESUMEN

Ionic liquids (ILs) have been reported to be a potential water and soil pollutant, whose toxicity has gained much attention in recent years. In this work, silkworm larvae were used as a novel in vivo model to assess the biotoxicity of ILs, which were performed by three steps. The first step was to determine the susceptibility of different silkworm strains to ILs. Data showed that Jingsong×haoyue was the most susceptible one among three silkworm strains (Jingsong×haoyue, P50, and Yi16) for evaluating the biological effects of ILs. The second step was to compare the toxicity of ILs with different structures using the larvae of Jingsong×haoyue. It was found that three representative ILs, 1-octyl-3-methylimidazole chloride ([C8mim]Cl), N-octyl-3-methylpyridine chloride ([C8mpy]Cl), and 1-octyl-3-methylimidazole tetrafluoroborate ([C8mim]BF4), had significant toxic effects on the growth and development of the larvae with 24 h median lethal concentration (24 h-LC50) values of 112.3, 156.3, and 68.9 µg g-1, respectively, indicating that the types of anions and cations had impacts on the toxicity of ILs. The last step was targeted at investigating responses of the larvae to the exposure of ILs. It was observed that remarkable physiological and biochemical responses occurred in different tissues of the larvae. For example, activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in different tissues increased significantly to form an active protective mechanism for alleviating the toxic effects of ILs. Additionally, an increase of malondialdehyde (MDA) contents was found in the larvae. The data suggested that ILs could induce lipid peroxidation and cellular damage, which may be the main reason for toxicity of ILs to the larvae. Therefore, silkworm larvae could be used as a susceptible and reliable in vivo model to evaluate the toxicity of ILs, and the results are helpful to reveal their toxic mechanism to insects.


Asunto(s)
Sustancias Peligrosas/toxicidad , Líquidos Iónicos/toxicidad , Animales , Aniones/química , Bombyx/metabolismo , Bombyx/fisiología , Catalasa/metabolismo , Cationes , Cloruros , Estudios de Factibilidad , Imidazoles , Larva/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído , Superóxido Dismutasa/metabolismo , Pruebas de Toxicidad
12.
Ecotoxicol Environ Saf ; 209: 111785, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33348254

RESUMEN

Heavy metals are considered contaminants that hazardously influence the healthy life of humans and animals as they are widely used in industry. Contact of youngsters and women at ages of parturition with lead (Pb+2) is a main related concern, which passes through the placental barricade and its better absorption in the intestine leads to flaws in the fetal developfment. However, the metals threaten animal and human life, in particular throughout developmental stages. Products existing in the nature have a major contribution to innovating chemo-preventives. As a naturally available polyphenol and necessary curcuminoid, curcumin (Cur) is a derivative of the herb Curcuma longa (L.) rhizome, which globally recognized as "wonder drug of life"; however, Cur has a limited clinical use as it is poorly dissolved in water. Therefore, to enhance its clinically relevant parameters, curcumin-loaded calcium carbonate (CaCO3@Cur) was synthesized by one step coprecipitation method as a newly introduced in this research. Initially, its structure was physio chemically characterized using FT-IR, FESEM and DLS equipment and then the cytotoxicity of lead when it was pretreated with Cur/CaCO3@Cur were assessed by MTT assay. Both Cur and CaCO3@Cur diminished the toxic effects of Pb+2 while the most protective effect on the Pb+2 cytotoxicity was achieved by pre-incubation of cells with CaCO3@Cur. Besides, the morphological changes of Pb+2-treated cells that were pre-incubated with or without Cur/CaCO3@Cur were observed by normal and florescent microscopes. A non-pharmacologic method that lowers the hazard of brain damage is exercise training that is capable of both improving and alleviating memory. In the current study, the role of regular aerobic training and CaCO3@Cur was assessed in reducing the risk of brain damage induced by lead nitrate contact. To achieve the mentioned goal, pregnant Balb/C mice were assigned to five groups (six mice/group) at random: negative and positive controls, aerobic training group and Cur and CaCO3@Cur treated (50 mg/kg/b.wt) trained groups that exposed to Pb+2 (2 mg/kg) by drinking water during breeding and pregnancy. With the completion of study, offspring were subjected to the behavioral tasks that was tested by step-through ORT, DLB, MWM and YM tests. As a result, having regular aerobic training and CaCO3@Cur co-administration with lead nitrate could reverse the most defected behavioral indicators; yet, this was not visible for both sexes and it seems that gender can also be a source of different effects in the animal's body. In fact, having regular aerobic training along with CaCO3@Cur supplementation during pregnancy may be encouraging protecting potential agents towards the toxicity of Pb+2 that could be recommended in the areas with high pollution of heavy metals.


Asunto(s)
Carbonato de Calcio , Disfunción Cognitiva/prevención & control , Curcumina , Suplementos Dietéticos , Sustancias Peligrosas/toxicidad , Plomo/toxicidad , Animales , Curcuma/efectos de los fármacos , Femenino , Humanos , Masculino , Ratones , Nitratos , Extractos Vegetales , Embarazo , Espectroscopía Infrarroja por Transformada de Fourier
13.
Ecotoxicol Environ Saf ; 209: 111819, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360786

RESUMEN

Cadmium (Cd) is a toxic trace element that can enter the environment with industrial waste and accumulate in the body but the health effects of Cd on ternary pigs are still lacking in research. In order to explore the effect of Cd on the apoptosis of pig spleen and its mechanism, this study chose ternary pig as the research object to detect relevant indicators in pig spleen under Cd exposure. The results of this study showed that Cd exposure can induce apoptosis by promoting the absorption of various toxic trace elements in the spleen and inducing oxidative stress. We also found that the mechanism of Cd-induced apoptosis is closely related to the VDR/CREB1 pathway. On the one hand, Cd exposure can activate VDR, and indirectly regulate the CYP family, affecting the normal function of the spleen. On the other hand, VDR and its downstream genes antagonize the toxicity of Cd by maintaining the stability of the mitochondrial-related endoplasmic reticulum membrane structure. Our research will help researchers to further understand the physiological toxicity of Cd.


Asunto(s)
Apoptosis/fisiología , Cadmio/toxicidad , Sustancias Peligrosas/toxicidad , Bazo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Porcinos
14.
Chemosphere ; 263: 128304, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33155548

RESUMEN

Gap junction intercellular communication (GJIC) is necessary for ovarian function, and it is temporospatially regulated during follicular development and ovulation. At outermost layer of the antral follicle, theca cells provide structural, steroidogenic, and vascular support. Inter- and extra-thecal GJIC is required for intrafollicular trafficking of signaling molecules. Because GJIC can be altered by hormones and endocrine disrupting chemicals (EDCs), we tested if any of five common EDCs (bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), perfluorooctanesulfonic acid (PFOS), and triphenyltin chloride (TPT)) can interfere with theca cell GJIC. Since most chemicals are reported to repress GJIC, we hypothesized that all chemicals tested, within environmentally relevant human exposure concentrations, will inhibit theca cell GJICs. To evaluate this hypothesis, we used a scrape loading/dye transfer assay. BPS, but no other chemical tested, enhanced GJIC in a dose- and time-dependent manner in ovine primary theca cells. A signal-protein inhibitor approach was used to explore the GJIC-modulatory pathways involved. Phospholipase C and mitogen-activated protein kinase (MAPK) inhibitors significantly attenuated BPS-induced enhanced GJIC. Human theca cells were used to evaluate translational relevance of these findings. Human primary theca cells had a ∼40% increase in GJIC in response to BPS, which was attenuated with a MAPK inhibitor, suggestive of a conserved mechanism. Upregulation of GJIC could result in hyperplasia of the theca cell layer or prevent ovulation by holding the oocyte in meiotic arrest. Further studies are necessary to understand in vitro to in vivo translatability of these findings on follicle development and fertility outcomes.


Asunto(s)
Sustancias Peligrosas/toxicidad , Fenoles/toxicidad , Sulfonas/toxicidad , Células Tecales/fisiología , Animales , Compuestos de Bencidrilo , Comunicación Celular , Comunicación , Conexina 43/metabolismo , Femenino , Uniones Comunicantes/metabolismo , Humanos , Oocitos/metabolismo , Ovinos , Transducción de Señal , Células Tecales/efectos de los fármacos , Células Tecales/metabolismo
15.
Chemosphere ; 262: 127891, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32799150

RESUMEN

Fluoride generally exists in the natural environment, and has been reported to induce serious environmental hazard to animals, plants, and even humans via ecological cycle. Silkworm, Bombyx mori, which showed significant growth and reproductivity reduction when exposed to fluoride, has become a model to evaluate the toxicity of fluoride. However, the detailed mechanism underlying fluoride toxicity and corresponding transport proteins remain unclear. In this study, we performed RNA-seq of the larval midgut and fat body with fluoride exposure and normal treatment. Differential analysis showed that there were 4405 differentially expressed genes in fat body and 4430 DEGs in midgut with fluoride stress. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we identified several key pathways involved in the fluoride exposure and poisoning. We focused on the oxidative phosphorylation and MAPK signal pathway. QRT-PCR confirmed that oxidative phosphorylation process was remarkably inhibited by fluoride exposure and resulted in the blocking of ATP synthesis. The MAPK signal pathway was stimulated via phosphorylation signal transduction. Moreover, by protein structure analysis combined with the DEGs, we screen 36 potential membrane proteins which might take part in transporting fluoride. Taken together, the results of our study expanded the underlying mechanisms of fluoride poisoning on silkworm larval growth and development, and implied potential fluoride transport proteins in silkworm.


Asunto(s)
Bombyx/fisiología , Fluoruros/toxicidad , Sustancias Peligrosas/toxicidad , Tejido Adiposo/metabolismo , Animales , Bombyx/metabolismo , Sistema Digestivo/metabolismo , Cuerpo Adiposo/metabolismo , Perfilación de la Expresión Génica/métodos , Inactivación Metabólica , Larva/genética , Transcriptoma/fisiología
16.
Environ Health Perspect ; 128(12): 127008, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33325755

RESUMEN

BACKGROUND: Humans are constantly being exposed to various xenobiotics at relatively low concentrations. To date, limited evidence is available to ascertain whether a complex xenobiotic mixture at human-relevant levels causes any health effect. Moreover, there is no effective method to pinpoint the contribution of each chemical toward such an effect. OBJECTIVES: This study aims to understand the responses of cells to a mixture containing 23 xenobiotics at human-relevant levels and develop a feasible method to decipher the chemical(s) that contribute significantly to the observed effect. METHODS: We characterized the metabolome and transcriptome of breast cancer cells (MCF-7) before and after exposure to the mixture at human-relevant levels; preexposure levels were derived from existing large-scale biomonitoring data. A high-throughput metabolomics-based "leave-one-out" method was proposed to understand the relative contribution of each component by comparing the metabolome with and without the particular chemical in the mixture. RESULTS: The metabolomic analysis suggested that the mixture altered metabolites associated with cell proliferation and oxidative stress. For the transcriptomes, gene ontology terms and pathways including "cell cycle," "cell proliferation," and "cell division" were significantly altered after mixture exposure. The mixture altered genes associated with pathways such as "genotoxicity" and "nuclear factor erythroid 2-related factor 2 (Nrf2)." Through joint pathways analysis, metabolites and genes were observed to be well-aligned in pyrimidine and purine metabolisms. The leave-one-out results showed that many chemicals made their contributions to specific metabolic pathways. The overall metabolome pattern of the absence of 2,4-dihyroxybenzophenone (DHB) or bisphenol A (BPA) showed great resemblance to controls, suggesting their higher relative contribution to the observed effect. DISCUSSION: The omics results showed that exposure to the mixture at human-relevant levels can induce significant in vitro cellular changes. Also, the leave one out method offers an effective approach for deconvoluting the effects of the mixture. https://doi.org/10.1289/EHP6641.


Asunto(s)
Sustancias Peligrosas/toxicidad , Metaboloma/efectos de los fármacos , Pruebas de Toxicidad , Transcriptoma/efectos de los fármacos , Humanos , Células MCF-7
17.
Ecotoxicol Environ Saf ; 203: 111055, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32888617

RESUMEN

The pollution level of potentially toxic elements (PTEs) in surface soils is detrimental to the ecosystem and human health. In this research, various indices such as an index of geo-accumulation (Igeo), contamination factor (CF), degree of contamination (DC), and principal component analysis (PCA) were implemented to identify and evaluate the soil PTEs pollution; and then human health risk assessment model used to establish the link between heavy metals pollution and human health in the urban region of south India. Results exhibited that the mean concentration of Cr, Cu, Ni and Zn were found to be 1.45-6.03 times greater than the geochemical background values. Cr and Cu were the most profuse PTEs measured in the soils. The pollution indices suggest that soil of the study region is mainly moderate to highly polluted. The non-carcinogenic health risk assessment proposed by the United States Environmental Protection Agency (USEPA) suggested the mean hazard indices (HIs) were below one which denotes no significant of non-carcinogenic risks to both children and adults. Furthermore, carcinogenic risk assessment results advised ~80% of cancer risk was caused by Cr contents, while other heavy metals indicate that neither children nor adults in the study region were of carcinogenic risks.


Asunto(s)
Carcinógenos/análisis , Monitoreo del Ambiente/métodos , Sustancias Peligrosas/análisis , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Suelo/química , Adulto , Carcinógenos/toxicidad , Niño , Ecosistema , Sustancias Peligrosas/toxicidad , Humanos , India , Metales Pesados/toxicidad , Medición de Riesgo , Contaminantes del Suelo/toxicidad , Estados Unidos , United States Environmental Protection Agency , Urbanización
18.
Ecotoxicol Environ Saf ; 206: 111329, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-32979722

RESUMEN

The aim of the study was to investigate the protective effects of selenium yeast (SeY) against necroptosis triggered by Cd via inhibition of oxidative stress and MAPK pathway in the liver of chicken. Two hundred 120-day-old layers were randomly divided into four groups and raised for 120 days. The histopathological examination showed that necrosis characteristics were observed in Cd-exposed chicken livers. The exposure of Cd significantly reduced the activities of SOD, GSH-Px and CAT while improving MDA level in both serum and liver of chickens (P < 0.05), and induced oxidative stress. The MLKL, Rip1, RIP3, ERK, JNK and P38 mRNA expression of Cd group were significantly higher than other three groups (P < 0.01), and those in the Se + Cd group were significantly higher than control group and Se group (P < 0.01). However, the mRNA expression level of caspase8 of Cd was significantly lower than other three groups (P < 0.01), and that in the Se + Cd group was significantly higher than control group and Se group (P < 0.01), so the supplement of SeY could improve these situations. Similar results were also detected at the protein level. The results of the present study indicated that Cd could induce oxidative stress, activate MAPK pathway and evoke necroptosis damage in chicken livers, whereas SeY had protective effects in preventing this kind of Cd-induced injury by inhibition of oxidative stress and down-regulation MAPK pathway.


Asunto(s)
Cadmio/toxicidad , Sustancias Peligrosas/toxicidad , Sustancias Protectoras/farmacología , Selenio/farmacología , Animales , Cadmio/metabolismo , Pollos/metabolismo , Suplementos Dietéticos , Hígado/efectos de los fármacos , Necroptosis , Estrés Oxidativo/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo
19.
Chemosphere ; 258: 127288, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32947659

RESUMEN

The discharge of toxic elements from tailings soils in the aquatic environments occurs chiefly in the presence of indigenous bacteria. The biotic components may interact in the opposite direction, leading to the formation of a passivation layer, which can inhibit the solubility of the elements. In this work, the influence of jarosite on the bio-immobilization of toxic elements was studied by native bacteria. In batch experiments, the bio-immobilization of heavy metals by an inhibitory layer was examined in the different aquatic media using pure cultures of Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans. A variety of analyses also investigated the mechanisms of metals bio-immobilization. Among different tests, the highest metal solubility yielded 99% Mn, 91% Cr, 95% Fe, and 78% Cu using A. ferrooxidans in 9KFe medium after ten days. After 22 days, these percentages decreased down to 30% Mn and about 20% Cr, Fe, and Cu, likely due to metal immobilization by biogenic jarosite. The formation of jarosite was confirmed by an electron probe micro-analyzer (EPMA), X-ray diffraction (XRD), and scanning electron microscope (SEM). The mechanisms of metal bio-immobilization by biogenic jarosite from tailings soil confirmed three main steps: 1) the dissolution of metal sulfides in the presence of Acidithiobacillus bacteria; 2) the nucleation of jarosite on the surface of sulfide minerals; 3) the co-precipitation of dissolved elements with jarosite during the bio-immobilization process, demonstrated by a structural study for jarosite. Covering the surface of soils by the jarosite provided a stable compound in the acidic environment of mine-waste.


Asunto(s)
Compuestos Férricos/química , Sustancias Peligrosas/análisis , Sulfatos/química , Acidithiobacillus , Acidithiobacillus thiooxidans , Bacterias , Sustancias Peligrosas/toxicidad , Metales Pesados , Minerales , Solubilidad , Sulfuros/química , Difracción de Rayos X
20.
Toxicol Lett ; 334: 1-3, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32916183

RESUMEN

The Chemical Countermeasures Research Program (CCRP) was established in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID/NIH) on behalf of the National Institutes of Health Office of the Director (NIH OD). It is a trans-NIH initiative to expedite the discovery and early development of medical countermeasures (MCMs) that can reduce mortality and serious morbidity during and after large consequence public health emergency involving the deliberate or accidental large-scale release of highly toxic chemicals (HTCs).


Asunto(s)
Planificación en Desastres/métodos , Ojo/efectos de los fármacos , Sustancias Peligrosas/toxicidad , Contramedidas Médicas , Neuropatía Óptica Tóxica/prevención & control , Humanos , National Institute of Allergy and Infectious Diseases (U.S.) , Salud Pública , Estados Unidos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA