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1.
Food Chem Toxicol ; 182: 114155, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37898232

RESUMEN

Icariin (ICA) is a natural flavonoid isolated from the traditional Chinese medicinal herb, Epimedium brevicornu Maxim. Although previous studies have reported that ICA exhibits various pharmacological activities, little is known about its toxicology. Herein, zebrafish embryos were exposed to ICA at 0, 2.5, 10, and 40 µM. In developmental analysis, reduced hatching rates, decreased body length, and abnormal swim bladder were found after treatment with 10 and 40 µM ICA. In addition, the ability of locomotor behavior was impaired by ICA. Two important thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), were tested. The exposure resulted in a remarkable alteration of T4 level and a significant decrease of the T3/T4 ratio in the 40 µM, indicating thyroid endocrine disruption. Furthermore, gene transcription analysis showed that genes involved in thyroid development (nkx2.1) and THs synthesis (tg) were up-regulated after ICA exposure. Significant down-regulation of iodothyronine deiodinase (dio1) was also observed in the 10 and 40 µM groups compared to the control. Taken together, our study first demonstrated that ICA caused developmental toxicity possibly through disrupting thyroid development and hormone synthesis. These results show that it is necessary to perform risk assessments of ICA in clinical practice.


Asunto(s)
Disruptores Endocrinos , Contaminantes Químicos del Agua , Animales , Pez Cebra , Larva , Hormonas Tiroideas , Glándula Tiroides , Contaminantes Químicos del Agua/toxicidad , Disruptores Endocrinos/toxicidad
2.
Ecotoxicol Environ Saf ; 256: 114899, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37060801

RESUMEN

Phenanthrene (Phe), one of the most frequently occurring pollutants in nature, can cause substantial damage to the human liver. Herbt Tea Essences (HTE), a kind of black tea extract with strong anti-inflammatory activity, can protect humans against disease. Currently, whether HTE can protect the liver from Phe-induced hepatotoxicity remains unclear. Herein, we explore the protective effects of HTE against Phe-induced hepatotoxicity. Our results showed that Phe exposure could significantly induce liver damage and increase serum hepatic enzyme levels in mice. HTE could prevent liver damage and recover the expression levels of inflammatory factors. Furthermore, we found that HTE suppressed the excessive activation of the nuclear transcription factor kappa-B and transforming growth factor-ß/SMAD signaling pathways to alleviate Phe-induced liver inflammation and fibrosis. Overall, our data showed that HTE treatment could be a new preventive means for Phe-induced liver disease.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías , Ratones , Humanos , Animales , Extractos Vegetales/farmacología , Hígado , FN-kappa B/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo ,
3.
Ecotoxicol Environ Saf ; 246: 114168, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36244174

RESUMEN

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.


Asunto(s)
Resistencia a la Insulina , Insulinas , Puntos Cuánticos , Ratones , Animales , Puntos Cuánticos/toxicidad , Fósforo , Glucemia
4.
Small Methods ; 5(3): e2001045, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-34927824

RESUMEN

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.


Asunto(s)
Ferroptosis , Puntos Cuánticos , Ferroptosis/genética , Fósforo/metabolismo , Puntos Cuánticos/toxicidad , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética
5.
J Hazard Mater ; 402: 122875, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33254732

RESUMEN

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.


Asunto(s)
Fósforo , Puntos Cuánticos , Supervivencia Celular , Humanos , Pulmón , Fósforo/toxicidad , Puntos Cuánticos/toxicidad , Especies Reactivas de Oxígeno
6.
Small ; 16(22): e2001371, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32338439

RESUMEN

Quantum dots (QDs) have numerous potential applications in lighting, engineering, and biomedicine. QDs are mainly excreted through the kidney due to their ultrasmall sizes; thus, the kidneys are target organs of QD toxicity. Here, an organoid screening platform is established and used to study the nephrotoxicity of QDs. Organoids are templated from monodisperse microfluidic Matrigel droplets and found to be homogeneous in both tissue structure and functional recapitulation within a population and suitable for the quantitative screening of toxic doses. Kidney organoids are proved displaying higher sensitivity than 2D-cultured cell lines. Similar to metal-containing QDs, black phosphorus (BP)-QDs are found to have moderate toxicity in the kidney organoids. The nephrotoxicity of BP-QDs are validated in both mice and human renal tubular epithelial cells. BP-QDs are also found to cause insulin insensitivity and endoplasmic reticulum (ER) stress in the kidney. Furthermore, ER stress-related IRE1α signaling is shown to mediate renal toxicity and insulin insensitivity caused by BP-QDs. In summary, this work demonstrates the use of constructed kidney organoids as 3D high-throughput screening tools to assess nanosafety and further illuminates the effects and molecular mechanisms of BP-QD nephrotoxicity. The findings will hopefully enable improvement of the safety of BP-QD applications.


Asunto(s)
Puntos Cuánticos , Animales , Endorribonucleasas , Humanos , Ratones , Organoides , Fósforo , Proteínas Serina-Treonina Quinasas , Puntos Cuánticos/toxicidad
7.
Mol Nutr Food Res ; 63(9): e1900072, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30811831

RESUMEN

SCOPE: ß-Carotene (BC), a substitute for vitamin A, is widely used for its benefits. The present study investigates whether in-utero BC administration can alter lipid and glucose homoeostasis in offspring. METHODS AND RESULTS: Pregnant mice are supplemented with BC (1 mg kg-1 weight) by oral gavage once every 3 days, for a total of six doses. Increased visceral fat may be caused by up-regulated PPARγ (peroxisome proliferator-activated receptor gamma) and RXRα/ß (retinoid X receptors) in liver and adipose tissue, and glucose intolerance is observed in F1 adult females prenatally supplemented with BC, while F1 males do not exhibit these symptoms. In females, increased serum leptin, resistin, and IL-6 and reduced adiponectin, caused by visceral obesity, may result in downregulated insulin receptor signaling in muscle and further account for glucose intolerance. Increased pancreatic ß-cell mass might compensate for the downregulated insulin gene (ins2). Increased glucagon and α-cell mass, accompanied by upregulated glucagon gene (gcg), might also be risk factors for the development of diabetes. CONCLUSIONS: Maternal supplementation with BC disturbs lipid metabolism and induces glucose intolerance in F1 female mice, suggesting that BC supplementation during pregnancy should be used with caution.


Asunto(s)
Glucosa/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , beta Caroteno/farmacología , Adipoquinas/sangre , Animales , Metilación de ADN , Suplementos Dietéticos , Estradiol/sangre , Femenino , Intolerancia a la Glucosa , Homeostasis , Insulina/metabolismo , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Ratones Endogámicos C57BL , Embarazo , Regiones Promotoras Genéticas , Receptor beta X Retinoide/genética , Receptor beta X Retinoide/metabolismo , Testosterona/sangre
8.
Environ Geochem Health ; 41(4): 1847-1860, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30066097

RESUMEN

Ocean acidification (OA) and crude oil pollution have been highlighted as some of the most pervasive anthropogenic influences on the ocean.In marine teleosts, early life-history stages are particularly vulnerable to disturbance by CO2-driven acidification as they lack pH-mediated intracellular regulation. Embryos exposed to trace levels of crude oil constituents dissolved in water exhibit a common syndrome of developmental abnormalities. So far, little is known about the combined effects of OA and crude oil on the early life history of marine fish. Eggs and larvae of the marine medaka (Oryzias melastigma) were treated with CO2 (1080 µatm atmospheric CO2), the water-soluble fraction (WSF) of crude oil (500 µg/L) and a CO2 (1080 µatm atmospheric CO2)/WSF (500 µg/L) mixture within 4 h after oviposition. Isolated and combined OA/WSF had no detectable effect on embryonic duration, egg survival rate and size at hatching. Histopathological anomalies of tissue and lipid metabolic disorder were significant when CO2 or WSF was given alone at 30 days of age. Combination of CO2 and WSF enhanced their toxicity compared to their separate administration. Since the early life-history stage of marine fish is thought to be impacted more heavily by increasing CO2 partial pressure (pCO2) levels and crude oil pollution, OA and crude oil pollution have the potential to act as an additional source of natural mortality.


Asunto(s)
Larva/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Oryzias/embriología , Contaminación por Petróleo/efectos adversos , Animales , Ecotoxicología , Embrión no Mamífero/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Concentración de Iones de Hidrógeno , Larva/crecimiento & desarrollo , Metabolismo de los Lípidos/genética , Oryzias/crecimiento & desarrollo , Oryzias/metabolismo , Oviposición/efectos de los fármacos , Petróleo/toxicidad , Agua de Mar/química , Contaminantes Químicos del Agua/toxicidad
9.
Chemosphere ; 191: 7-16, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29024898

RESUMEN

The water-soluble fraction (WSF) of crude oil plays an important role in the toxicity of crude oil in aquatic environments. Heavy metals, such as lead (Pb) are also important environmental contaminants, which can reach aquatic systems via the effluents of industrial, urban and mining sources. In the present study, we investigated whether maternal and embryonic exposure to the WSF (5, 50 µg/L) or Pb (10, 100 µg/L) could induce behavioral abnormalities in zebrafish. Our results showed that maternal and embryonic exposure to the WSF (5, 50 µg/L) and Pb (10, 100 µg/L) induced swimming activity alterations in larval and juvenile zebrafish. In 15 days post-fertilization (dpf) larval zebrafish, the distance moved was significantly increased in the groups treated with the WSF (5, 50 µg/L), but the angular velocity and turn angle were decreased after treatment with the WSF (5, 50 µg/L) or Pb (10, 100 µg/L). In 30 dpf juvenile zebrafish, the distance moved was markedly decreased in both groups treated with the WSF (5, 50 µg/L) and the Pb (10 µg/L) group, but the percentage of zebrafish moving up and the inter-fish distance of two juvenile fish were increased after treatment with the WSF (5, 50 µg/L) or Pb (10, 100 µg/L). Maternal and embryonic exposure to the WSF (5, 50 µg/L) or Pb (10, 100 µg/L) likely impaired the brain neurons growth and induced behavioral abnormalities in the larval and juvenile zebrafish. Furthermore, the expressions of some key genes, which were associated with calcium channels, behavioral development or the metabolism of environmental contaminants, were changed.


Asunto(s)
Embrión no Mamífero/anomalías , Plomo/toxicidad , Petróleo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Larva , Plomo/metabolismo , Metales Pesados/metabolismo , Petróleo/metabolismo , Natación , Contaminantes Químicos del Agua/análisis , Pez Cebra/anomalías , Pez Cebra/embriología , Pez Cebra/metabolismo
10.
Aquat Toxicol ; 104(3-4): 263-9, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21641294

RESUMEN

Both triphenyltin (TPT) and tributyltin (TBT) have been used as ingredients of antifouling biocides. However, far fewer studies addressing the reproductive toxicity of TPT on fishes are available than for TBT. The present study was conducted to investigate the effects of TPT at environmentally relevant concentrations on testicular development in male rockfish Sebastiscus marmoratus and to gain insight into its mechanism of action. After exposure for 48 days, the gonadosomatic index had decreased, and there was a reduced number of mature sperm and an abundance of the late stages of spermatocysts in the testes. Although the testosterone levels in the testes were elevated and the 17ß-estradiol levels were decreased, spermatogenesis was suppressed. The activity of γ-glutamyl transpeptidase (which is used as a Sertoli cell marker) was decreased after TPT exposure, and serious interstitial fibrosis was observed in the interlobular septa of the testes exposed to TPT. The increased expression of cGnRH-II (chicken-II type gonadotropin-releasing hormone) and sGnRH (salmon-type GnRH), and the decreased expression of LHß (luteinizing hormone) in the fish brains were detected. The expression of FSHß (follicle-stimulating hormone) was decreased at day 21, while was increased slightly at day 48. The changes of cGnRH-II, sGnRH, FSHß and LHß mRNA levels might have mainly resulted from the alteration of the sex steroids via feedback mechanisms. The decrease of the FSHß mRNA might have been one of the reasons causing the dysfunction of Sertoli cells, which play a critical role during spermatogenesis. The results suggested that TPT could perturb the function of hypothalamus-pituitary-gonad axis, and inhibiting the spermatogenesis.


Asunto(s)
Desinfectantes/toxicidad , Peces/fisiología , Compuestos Orgánicos de Estaño/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Secuencia de Bases , Encéfalo/metabolismo , Desinfectantes/metabolismo , Hormona Folículo Estimulante/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Gónadas/efectos de los fármacos , Gónadas/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Hormona Luteinizante/metabolismo , Masculino , Datos de Secuencia Molecular , Compuestos Orgánicos de Estaño/metabolismo , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , ARN Mensajero/metabolismo , Espermatogénesis/efectos de los fármacos , Testosterona/metabolismo , Compuestos de Trialquiltina/toxicidad , Contaminantes Químicos del Agua/metabolismo
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