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1.
Environ Health Prev Med ; 26(1): 31, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678156

RESUMO

BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 µg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 µg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION: These results suggest that exposure to 5 and 50 µg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.


Assuntos
Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Fenóis/toxicidade , Sulfonas/toxicidade , Testículo/efeitos dos fármacos , Animais , Biomarcadores , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo , Testículo/fisiopatologia , Testes de Toxicidade Crônica
2.
Ecotoxicol Environ Saf ; 212: 111968, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33550083

RESUMO

Despite the fact that copper (Cu) is a vital micronutrient to maintain body function, high doses of Cu through environmental exposure damage various organs, especially the liver, which is the main metabolic organ. To investigate the influence of long-term Cu-induced toxicity on mitophagy and apoptosis in rat liver, 96 seven-month-old male Sprague-Dawley rats were fed TBCC for 24 weeks. The results revealed that exposure to high Cu concentrations could promote oxidative stress liver injury by increasing the hepatic function index (ALT, AST and ALP) and MDA content, while reducing the activity of antioxidant enzymes (T-SOD, GSH-Px and CAT) related to oxidative stress. Consistent with histopathological observations, proper dietary Cu (15-60 mg/kg) could improve antioxidant stress levels and induce a dose-dependent increase in the mRNA expression of mitophagy-related genes, whereas a high Cu concentration (120 mg/kg) could cause severe liver impairment and ultrastructural changes and a reduction in mitophagosomes, accompanied by downregulation of Atg5, Beclin1, Pink1, Parkin, NIX, P62 and LC3B. The expression of apoptosis-related genes (Bax, Bax/Bcl-2, Caspase3, Cytc and p53) and proteins (Caspase3 and p53) was upregulated with the addition of dietary Cu. The results demonstrated that an appropriate dose of TBCC could improve liver function by promoting mitophagy and Cu enzymes that play antioxidative roles, while the accumulation of excess Cu could induce liver lesions by enhancing apoptosis and inhibiting mitophagy pathways.


Assuntos
Cloretos/toxicidade , Cobre/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Sulfato de Cobre/análise , Dieta , Fígado/metabolismo , Masculino , Mitofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Crônica
3.
Chemosphere ; 270: 129418, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33423002

RESUMO

Extensive use of neonicotinoids and fipronil, which are popular systemic insecticides used in Japanese rice paddies, has raised concerns about their impacts on nontarget aquatic organisms such as amphibians. This study employed premetamorphic tadpoles of Silurana tropicalis and addressed the toxicity of four neonicotinoids (acetamiprid, clothianidin, dinotefuran, and imidacloprid) and fipronil. Acute toxicity tests were conducted under a 96-h semistatic exposure regime and median lethal concentration (LC50) values were calculated at 24-h intervals. All LC50 values of the four neonicotinoids exceeded 100 mg/L, suggesting their low acute toxicity to amphibians. Fipronil yielded much lower LC50 values (3.00-1.34 mg/L) and was highly toxic compared to the four neonicotinoids. Additionally, exposure to fipronil at >1 mg/L induced axial malformations, suggesting its teratogenicity. However, the LC50 values of fipronil were three orders of magnitude higher than the realistic concentrations in paddy water. Chronic toxicity tests were conducted with morphometric, gravimetric, and thyroid-histological endpoints. Premetamorphic tadpoles were exposed to each insecticide at two test concentrations: 0.1 and 1.0 mg/L for the four neonicotinoids; and 1/100 and 1/10 of the 96-h LC50 value for fipronil. Exposure to each insecticide continued until all tadpoles in the control reached late prometamorphic stages or the initial stage of metamorphic climax. At test termination, all insecticides showed no significant differences in any of the endpoints between the respective controls and chemical exposure groups. Overall, our results suggest that these insecticides alone do not directly affect amphibians through their larval stages at concentrations that likely occur in paddy water.


Assuntos
Inseticidas , Poluentes Químicos da Água , Animais , Inseticidas/toxicidade , Larva , Neonicotinoides/toxicidade , Nitrocompostos , Pirazóis , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade
4.
Ecotoxicol Environ Saf ; 208: 111747, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396073

RESUMO

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 µg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males.


Assuntos
Diazepam/toxicidade , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Diazepam/administração & dosagem , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Natação , Peixe-Zebra/metabolismo , Ácido gama-Aminobutírico/farmacologia
5.
Ecotoxicol Environ Saf ; 212: 111979, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33513482

RESUMO

Silicon oxide (SiO2) nanostructures (SiO2NS) are increasingly being incorporated into an array of products, notably in the food, pharmaceutical, medical industries and in water treatment systems. Amorphous SiO2NS have low toxicity, however, due to their great versatility, superficial modifications can be made and these altered structures require toxicological investigation. In this study, SiO2NS were synthetized and amine-functionalized with the molecules (3-aminopropyl)triethoxysilane (APTMS) and 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane (AEAEAPTMS), named SiO2NS@1 and SiO2NS@3, respectively. The bare SiO2NS, SiO2NS@1 and SiO2NS@3 samples were characterized and the influence of the culture medium used in the toxicological assays was also evaluated. The effect of amine functionalization of SiO2NS was investigated through acute and chronic toxicity assays with Daphnia magna. Modifications to ultrastructures of the intestine and eggs of these organisms were observed in TEM and SEM analysis. The toxicity was influenced by the surface modifications and a possible Trojan horse effect was highlighted, particularly in the case of chronic exposure. Exposure to all NSs promoted alterations in the microvilli and mitochondria of the D. magna intestine and some damage to egg cells was also observed. The results demonstrate the importance of carrying out a full characterization of these materials, since surface modifications can enhance their toxic potential.


Assuntos
Daphnia/fisiologia , Nanoestruturas/toxicidade , Dióxido de Silício/toxicidade , Aminas , Animais , Bioensaio , Daphnia/efeitos dos fármacos , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade
6.
Ecotoxicol Environ Saf ; 209: 111848, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421672

RESUMO

Fungicides pose a risk for crustacean leaf shredders serving as key-stone species for leaf litter breakdown in detritus-based stream ecosystems. However, little is known about the impact of strobilurin fungicides on shredders, even though they are presumed to be the most hazardous fungicide class for aquafauna. Therefore, we assessed the impact of the strobilurin azoxystrobin (AZO) on the survival, energy processing (leaf consumption and feces production), somatic growth (growth rate and molting activity), and energy reserves (neutral lipid fatty and amino acids) of the amphipod crustacean Gammarus fossarum via waterborne exposure and food quality-mediated (through the impact of leaf colonizing aquatic microorganisms) and thus indirect effects using 2 × 2-factorial experiments over 24 days. In a first bioassay with 30 µg AZO/L, waterborne exposure substantially reduced survival, energy processing and affected molting activity of gammarids, while no effects were observed via the dietary pathway. Furthermore, a negative growth rate (indicating a body mass loss in gammarids) was induced by waterborne exposure, which cannot be explained by a loss in neutral lipid fatty and amino acids. These energy reserves were increased indicating a disruption of the energy metabolism in G. fossarum caused by AZO. Contrary to the first bioassay, no waterborne AZO effects were observed during a second experiment with 15 µg AZO/L. However, an altered energy processing was determined in gammarids fed with leaves microbially colonized in the presence of AZO, which was probably caused by fungicide-induced effects on the microbial decomposition efficiency ultimately resulting in a lower food quality. The results of the present study show that diet-related strobilurin effects can occur at concentrations below those inducing waterborne toxicity. However, the latter seems to be more relevant at higher fungicide concentrations.


Assuntos
Anfípodes/fisiologia , Fungicidas Industriais/toxicidade , Estrobilurinas/toxicidade , Poluentes Químicos da Água/toxicidade , Anfípodes/efeitos dos fármacos , Animais , Dieta , Ecossistema , Folhas de Planta/metabolismo , Pirimidinas , Rios , Testes de Toxicidade Crônica
7.
Ecotoxicol Environ Saf ; 207: 111305, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32942101

RESUMO

Poultry litter is one of the main sources of fluoroquinolones (FQs) in agricultural soils. In this study, our main goal was to investigate FQ-contaminated poultry litter effects on Eisenia andrei earthworms. To achieve this, acute and chronic tests covered several endpoints, such as avoidance, biomass, lethality, reproduction and changes to immune cells. FQs (enrofloxacin and ciprofloxacin) were determined in a poultry litter sample through high performance liquid chromatography with a fluorescence detector. The avoidance test indicates that poultry litter strongly repels earthworms, even at the lowest concentration (50 g kg-1). In the acute test, the lethal concentration of poultry litter to 50% of the earthworms (LC50), was estimated at 28.5 g kg-1 and a significant biomass loss (p < 0.05) occurred at 40 g kg-1. In the chronic test, a significant reproduction effect was observed at 20 g kg-1. Cell typing, density and feasibility indicated significant effects ranging from 5 to 20 g kg-1. A high risk quotient was estimated based on recommended poultry litter applications in field studies. Although FQ contamination in poultry litter and soils has been widely reported in previous studies, this is, to the best of our knowledge, the first toxicological assessment concerning earthworms exposed to FQ-contaminated poultry litter.


Assuntos
Fluoroquinolonas/toxicidade , Oligoquetos/efeitos dos fármacos , Aves Domésticas , Poluentes do Solo/toxicidade , Solo/química , Resíduos Sólidos/análise , Agricultura , Animais , Biomassa , Fluoroquinolonas/análise , Dose Letal Mediana , Oligoquetos/crescimento & desenvolvimento , Reprodução/efeitos da radiação , Poluentes do Solo/análise , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica
8.
Ecotoxicol Environ Saf ; 209: 111794, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33348256

RESUMO

Microplastics (MPs) in the form of microfibres (MFs) are of great concern because of their size and increasing abundance, which increase their potential to interact with or be ingested by aquatic organisms. Although MFs are the dominant shape of MPs ingested by sea cucumbers in habitats, their effect on sea cucumbers remains unclear. This study examined the effect of dietary exposure to MFs on the growth and physiological status of both juvenile and adult Apostichopus japonicus sea cucumbers. MFs were mixed into the diet of sea cucumbers for 60 d at environmentally relevant concentrations of 0.6 MFs g-1, 1.2 MFs g-1 and 10 MFs g-1. Dietary exposure to MFs, with concentrations at or above those commonly found in the habitats, did not significantly affect the growth and faecal production rate of either juvenile or adult sea cucumbers. However, a disruption in immunity indices (acid phosphatase and alkaline phosphatase activity) and oxidative stress indices (total antioxidant capacity and malondialdehyde content) was observed in juvenile and adult sea cucumbers, indicating that these indices might be useful as potential biomarkers of the exposure to MF ingestion in sea cucumbers. This study provides insights into the toxicity mechanism of MF ingestion in a commercially and ecologically important species.


Assuntos
Microplásticos/toxicidade , Pepinos-do-Mar/fisiologia , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes , Dieta , Ingestão de Alimentos , Imunidade Inata , Malondialdeído , Plásticos , Stichopus/crescimento & desenvolvimento
9.
Ecotoxicol Environ Saf ; 207: 111563, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254417

RESUMO

Exposure to endocrine-disrupting chemicals (EDCs) has been hypothesized as a cause of declining sheep reproductive efficiency. Understanding the long-term effects of EDCs such as heavy metals on reproductive health requires investigation in 'real life' of sheep that are reared in industrial areas. The aim of this study was to evaluate the effect of long-term exposure of Kermani rams to high levels of environmental heavy metals probably emitted from a copper smelter at KhatoonAbad in ShahreBabak, Kerman province. Testicular characteristics were determined in randomly-selected rams (3-4 years old) at 4 directions (south, north, east, and west) and 4 distances (10, 20, 30, and 40 km) from the smelter. Testicular trace element contents, size, serum testosterone, histological attributes and seminal characteristics, except semen volume, were affected by both the direction and the distance from the smelter (P < 0.05). Testicular contents of Pb, Cd, Cr, and Ni, and sperm abnormalities were higher at 10 km south from the smelter and lower at 40 km west. Other parameters were higher at 40 km west and lower at 10 km south. Interestingly, the testicular contents of Cu at 10 km south were lower and associated with higher sperm abnormalities in the rams reared closer to the smelter. The highest weight, length and circumference of the testis were found at 40 km west. The lowest concentration of testosterone was observed at 10 km south, being 92.6% lower than the highest values obtained at 40 km west. The diameter of seminiferous tubules and epithelial height at 10 km south were 8.9% and 27.5% lower than the highest values obtained at 40 km west. A positive correlation between Pb, Cd, Cr and Ni contents in the testis with sperm abnormalities, and a negative correlation between these elements with the other parameters were found. It was concluded that long-term exposure to heavy metals might have been a cause of decreased fertility in rams and probably other living species in this region.


Assuntos
Poluentes Ambientais/toxicidade , Metais Pesados/toxicidade , Testículo/efeitos dos fármacos , Animais , Cobre/toxicidade , Masculino , Reprodução , Análise do Sêmen/veterinária , Ovinos , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Testículo/fisiologia , Testosterona/sangue , Testes de Toxicidade Crônica , Oligoelementos/metabolismo
10.
Chemosphere ; 262: 127880, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32777607

RESUMO

BACKGROUND: Bisphenol A (BPA) is a well-known endocrine disruptor that affects male fertility. However, the main biological events through which BPA affects spermatogenesis remain to be identified. METHODS: Adult male mice were treated by feeding with drinking water containing BPA (0.2 µg/ml, 20 µg/ml, 200 µg/ml, respectively) for two months. Testes were collected for protein extraction or for immunohistochemical analysis. Epididymal spermatozoa were collected for sperm quality evaluation and male fertility assay by in vitro fertility (IVF). Serums were collected for detection of testosterone levels. Proteins associated with germ cell proliferation, meiosis, blood-testis barrier, and steroidogenesis production were examined in BPA-treated and control mice testes. CCK8 assay was used to detect the effect of BPA on the proliferation of GC-1 and GC-2 cells. RESULTS: The BPA-treated mice were characterized by decreased sperm quality, serum testosterone levels and, sub-fertile phenotype characterizing with low pregnancy rates and reduced fertilization efficiency. In lower BPA (0.2 µg/ml) treatment, PCNA and PLZF were down-expressed that indicated impaired germ cell proliferation. SYCP3 was down-expressed in BPA-treated mice, but expressions of other proteins associated with meiosis and blood-testis barrier were not significantly altered. CYP11A1 and HSD3B1 were down-expressed in BPA-treated mice that demonstrated reduced steroidogenesis activity. BPA has a concentration-dependent inhibition effect on the proliferation of GC-1 and GC-2 cells. Conclusively, low doses BPA exposure reduced mice sperm quality mainly by impairing germ cell proliferation, leading to reduced male fertility. The study would provide relevant information for investigation on molecular mechanisms and protective strategy on male production.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Espermatozoides/fisiologia , Animais , Proliferação de Células/efeitos dos fármacos , Disruptores Endócrinos/metabolismo , Epididimo/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Camundongos , Gravidez , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testes de Toxicidade Crônica
11.
Aquat Toxicol ; 228: 105646, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33011648

RESUMO

2,4-dinitrophenol (2,4-DNP) is a phenolic compound used as a wood preservative or pesticide. The chemical is hazardous to freshwater organisms. Although 2,4-DNP poses ecological risks, only a few of its aquatic environmental risks have been investigated and very limited guidelines for freshwater aquatic ecosystems have been established by governments. This study addresses the paucity of 2,4-DNP toxicity data for freshwater ecosystems and the current lack of highly reliable trigger values for this highly toxic compound. We conducted acute bioassays using 12 species from nine taxonomic groups and chronic assays using five species from four taxonomic groups to improve the quality of the dataset and enable the estimation of protective concentrations based on species sensitivity distributions. The acute and hazardous concentrations of 2,4-DNP in 5% of freshwater aquatic species (HC5) were determined to be 0.91 (0.32-2.65) mg/L and 0.22 (0.11-0.42) mg/L, respectively. To the best of our knowledge, this is the first report of a suggested chronic HC5 for 2,4-DNP and it provides the much-needed fundamental data for the risk assessment and management of freshwater ecosystems.


Assuntos
2,4-Dinitrofenol/análise , Ecossistema , Monitoramento Ambiental , Água Doce/química , Praguicidas/toxicidade , Poluentes Químicos da Água/análise , Animais , Organismos Aquáticos/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Chlamydomonas/efeitos dos fármacos , Clorofíceas/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Euglena/efeitos dos fármacos , Oryzias , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Especificidade da Espécie , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Qualidade da Água
12.
Ecotoxicol Environ Saf ; 204: 110977, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32739673

RESUMO

Indirect oxidation induced by reactive free radicals, such as hydroxyl radical (HO), sulfate radical (SO4-) and carbonate radical (CO3-), plays an important or even crucial role in the degradation of micropollutants. Thus, the coadjutant degradation of phenacetin (PNT) by HO, SO4- and CO3-, as well as the synergistic effect of O2 on HO and HO2 were studied through mechanism, kinetics and toxicity evaluation. The results showed that the degradation of PNT was mainly caused by radical adduct formation (RAF) reaction (69% for Г, the same as below) and H atom transfer (HAT) reaction (31%) of HO. For the two inorganic anionic radicals, SO4- initiated PNT degradation by sequential radical addition-elimination (SRAE; 55%), HAT (28%) and single electron transfer (SET; 17%) reactions, while only by HAT reaction for CO3-. The total initial reaction rate constants of PNT by three radicals were in the order: SO4- > HO > CO3-. The kinetics of PNT degradation simulated by Kintecus program showed that UV/persulfate could degrade target compound more effectively than UV/H2O2 in ultrapure water. In the subsequent reaction of PNT with O2, HO and HO2, the formation of mono/di/tri-hydroxyl substitutions and unsaturated aldehydes/ketones/alcohols were confirmed. The results of toxicity assessment showed that the acute and chronic toxicity of most products to fish increased and to daphnia decreased, and acute toxicity to green algae decreased while chronic toxicity increased.


Assuntos
Carbonatos/toxicidade , Peróxido de Hidrogênio/toxicidade , Fenacetina/toxicidade , Sulfatos/toxicidade , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Animais , Carbonatos/química , Clorófitas/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Peixes , Peróxido de Hidrogênio/química , Íons/química , Íons/toxicidade , Cinética , Modelos Químicos , Oxigênio/química , Fenacetina/química , Sulfatos/química , Água/química
13.
Ecotoxicol Environ Saf ; 202: 110940, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800223

RESUMO

Recent evidence indicates that chronic, low-dose exposure to mixtures of pesticides can cause adverse responses in a variety of cells, tissues and organs, although interactions between pesticides circulating in the blood and cancer cells remain largely unexplored. The aim of this study was to investigate the potential of a mixture of four pesticides to induce multidrug resistance against the chemotherapeutic agents cisplatin, 5-fluorouracil and temozolomide in the human U87 glioblastoma cell line, and to explore the molecular mechanisms underlying this resistance. We found that the repeated administration of the pesticide mixture (containing the insecticides chlorpyrifos-ethyl and deltamethrin, the fungicide metiram, and the herbicide glyphosate) induced a strong drug resistance in U87 cells. The resistance was durable and transferred to subsequent cell generations. In addition, we detected a significant over-expression of the ATP-binding cassette (ABC) membrane transporters P-gp/ABCB1 and BRCP/ABCG2 as well as a glutathione-S-transferase (GST)/M1-type cellular detoxification function, known to have important roles in multidrug resistance, thus providing molecular support for the acquired multidrug resistance phenotype and shedding light on the mechanism of resistance. We further determined that there was lower mortality in the resistant brain tumor cells and that the mitochondrial apoptosis pathway was activated at a lower rate after chemotherapy compared to non-resistant control cells. In addition, multidrug-resistant cells were found to have both higher motility and wound-healing properties, suggesting a greater metastatic potential. Our results suggest that the investigation of P-gp, BRCP and GST/M1 multidrug resistance gene expression and/or protein levels in biopsy specimens of brain tumor patients who were at risk of pesticide exposure could be beneficial in determining chemotherapy dose and prolonging patient survival.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Praguicidas/toxicidade , Testes de Toxicidade Crônica , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/farmacologia
14.
PLoS One ; 15(8): e0237163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764792

RESUMO

In bovine mammary glands, the ABCG2 transporter actively secretes xenobiotics into dairy milk. This can have significant implications when cattle are exposed to pesticide residues in feed. Recent studies indicate that the fungicide prochloraz activates the aryl hydrocarbon receptor (AhR) pathway, increasing bovine ABCG2 (bABCG2) gene expression and efflux activity. This could enhance the accumulation of bABCG2 substrates in dairy milk, impacting pesticide risk assessment. We therefore investigated whether 13 commonly used pesticides in Europe are inducers of AhR and bABCG2 activity. MDCKII cells expressing mammary bABCG2 were incubated with pesticides for up to 72 h. To reflect an in vivo situation, applied pesticide concentrations corresponded to the maximum residue levels (MRLs) permitted in bovine fat or muscle. AhR activation was ascertained through CYP1A mRNA expression and enzyme activity, measured by qPCR and 7-ethoxyresorufin-Ο-deethylase (EROD) assay, respectively. Pesticide-mediated increase of bABCG2 efflux activity was assessed using the Hoechst 33342 accumulation assay. For all assays, the known AhR-activating pesticide prochloraz served as a positive control, while the non-activating tolclofos-methyl provided the negative control. At 10-fold MRL concentrations, chlorpyrifos-methyl, diflufenican, ioxynil, rimsulfuron, and tebuconazole significantly increased CYP1A1 mRNA levels, CYP1A activity, and bABCG2 efflux activity compared to the vehicle control. In contrast, dimethoate, dimethomorph, glyphosate, iprodione, methiocarb and thiacloprid had no impact on AhR-mediated CYP1A1 mRNA levels, CYP1A activity or bABCG2 efflux. In conclusion, the MDCKII-bABCG2 cell model proved an appropriate tool for identifying AhR- and bABCG2-inducing pesticides. This provides an in vitro approach that could reduce the number of animals required in pesticide approval studies.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Alternativas aos Testes com Animais/métodos , Fungicidas Industriais/toxicidade , Receptores de Hidrocarboneto Arílico/agonistas , Testes de Toxicidade Crônica/métodos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/agonistas , Animais , Bovinos , Cães , Alemanha , Lactação/efeitos dos fármacos , Células Madin Darby de Rim Canino , Receptores de Hidrocarboneto Arílico/metabolismo , Proteínas Recombinantes/metabolismo
15.
Arch Environ Contam Toxicol ; 79(3): 298-309, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32860087

RESUMO

Aquatic environments are constantly exposed to a cocktail of contaminants mainly due to human activities. As polluted ecosystems may simultaneously present other multiple natural stressors, the objective of the present study was to evaluate joint effect of stressors (natural and anthropogenic) on life history traits of the Neotropical cladoceran, Ceriodaphnia silvestrii. For this purpose, the effects of water conditioned with predator kairomones (fish) and environmental concentrations (sublethal) of two pesticides widely used in sugarcane monoculture in Brazil, the insecticide Regent® 800 WG (active ingredient-a.i. fipronil) and the herbicide DMA® 806 BR (a.i. 2,4-D) were evaluated using chronic toxicity testing, isolated and in mixture, for this cladoceran species. The environmental risks of pesticides for tropical freshwater biota were also estimated from the risk quotient MEC/PNEC. Among the characteristics of the life history of C. silvestrii evaluated after 8 days of exposure, compared with the mean value of control, the age of primiparous females was not affected by any evaluated treatment. However, species average survival decreased in the treatment of kairomones mixed with fipronil (FK) and in the treatment with a mixture of fipronil, 2,4-D, and kairomones (MFKD). The body length of maternal females was shorter than in the control after exposure in treatments with only kairomones (K) and FK. Fecundity of this cladoceran was reduced when exposed to FK and MFKD treatments, and the intrinsic rate of population increase significantly decreased for organisms exposed to treatment with fipronil (F) and to mixtures of fipronil and 2,4-D (MFD), MFDK, and FK. The results indicated that the combination of anthropogenic and natural stressors causes changes in C. silvestrii life history traits, which can contribute to the decline in populations, and our preliminary risk assessment results are a matter of concern regarding biota conservation.


Assuntos
Ácido 2,4-Diclorofenoxiacético/toxicidade , Cladóceros/efeitos dos fármacos , Traços de História de Vida , Feromônios/toxicidade , Pirazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Brasil , Ecossistema , Feminino , Fertilidade/efeitos dos fármacos , Peixes/metabolismo , Água Doce/química , Testes de Toxicidade Crônica
16.
Ecotoxicology ; 29(9): 1462-1475, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32860623

RESUMO

Brazil is the largest producer of sugarcane and the world's top pesticide market. Therefore, environmental consequences are of concern. The aim of the present study was to evaluate the acute and chronic toxicity of pesticide formulations largely used in sugarcane crops: the herbicide DMA® 806 BR (a.i. 2,4-D) and the insecticide Regent® 800 WG (a.i. fipronil), isolated and in mixture, to the Neotropical cladoceran Ceriodaphnia silvestrii. Toxicity tests with the individual formulated products indicated 48h-EC50 values of 169 ± 18 mg a.i./L for 2,4-D and 3.9 ± 0.50 µg a.i./L for fipronil. In the chronic tests, the 8d-EC50 values for reproduction were 55 mg a.i./L (NOEC/LOEC: 50/60 mg a.i./L) and 1.6 µg a.i./L (NOEC/LOEC: 0.40/0.80 µg a.i./L) for 2,4-D and fipronil, respectively. A significant decrease in reproduction of C. silvestrii in all concentrations tested of fipronil, except at the lowest, was observed. Regarding 2,4-D, the organisms had total inhibition of reproduction in the two highest concentrations. Probably your energy reallocation was focused (trade-off) only on its survival. The acute pesticide mixture toxicity (immobility) revealed a dose level dependent deviation with antagonism at low and synergism at high concentrations. For chronic mixture (reproduction) toxicity, antagonism occurred as a result of the interaction of the pesticides. Based on our results and concentrations measured in Brazilian water bodies, fipronil represents ecological risks for causing direct toxic effects on C. silvestrii. These results are worrisome given that agricultural production is likely to increase in the coming years.


Assuntos
Ácido 2,4-Diclorofenoxiacético/toxicidade , Cladóceros/fisiologia , Praguicidas/toxicidade , Pirazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Brasil , Ecossistema , Inseticidas , Reprodução , Testes de Toxicidade , Testes de Toxicidade Crônica
17.
Bull Environ Contam Toxicol ; 105(2): 244-249, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32556691

RESUMO

The aim of the study was to assess the effects of silver nanoparticles (AgNPs1 = 2.7 d·nm, AgNPs2 = 6.5 d·nm) and silver nitrate (AgNO3) on Enchytraeus crypticus and Folsomia candida using toxicity tests (OECD Guideline 220, 232). A 28-day chronic toxicity study was performed to evaluate the reproduction and mortality rate. E. crypticus reproduction was more sensitive to AgNO3 with a 28dEC50 of 86.40 (62.52-119.4) mg·kg-1 dry weight (d.w.) compared to AgNPs1 (28dEC50 = 119.3 (60.4-235.6) mg·kg-1 d.w). Similarly, the reproduction of F. candida was inhibited the most by AgNO3 with a 28dEC50 of 126.2 (104.2-152.9) mg·kg-1 d.w. followed by AgNPs1 (28dEC50 = 158.7 (64.05-393.2) mg·kg-1 d.w.) and AgNPs2 (28dEC50 = 206.4 (181.9-234.1) mg·kg-1 d.w.). No mortalities were observed for tested soil invertebrates exposed to AgNPs at concentrations up to 166 mg·kg-1 d.w. of AgNPs1 and 300 mg·kg-1 d.w. of AgNPs2, respectively. It was found that silver ions are more toxic in comparison with AgNPs.


Assuntos
Artrópodes/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Oligoquetos/efeitos dos fármacos , Nitrato de Prata/toxicidade , Prata/toxicidade , Poluentes do Solo/toxicidade , Animais , Íons , Nanopartículas Metálicas/química , Reprodução/efeitos dos fármacos , Prata/química , Solo/química , Solo/normas , Poluentes do Solo/química , Testes de Toxicidade Crônica
18.
Chemosphere ; 254: 126874, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32361543

RESUMO

Okadaic acid (OA), one of the most important phycotoxins, is widely distributed around the world, concerning diarrheic shellfish poisoning (DSP), and even colorectal cancer. Here, we found that long-term exposure of OA at a low dose (80 µg kg-1 body weight) had certain effects on colonic microbiotas and tract in rat. In the OA-exposed rat, colonic epithelium layer was damaged, and relative abundance of some microbiotas were significantly changed, especially genera in Clostridiales. However, no intestinal inflammation or significant disease was observed. Combined with the increase in relative abundance of some genera in Clostridiales induced by OA in the fermentation experiment, we proposed that OA could cause damage to the intestinal epithelium and increase the relative abundance of pathogenic bacteria, thereby increasing the probability of contact between intestinal epithelium and pathogenic bacteria and leading to an easier pathogenicity.


Assuntos
Carcinógenos/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Ácido Okadáico/toxicidade , Animais , Colo , Inflamação , Mucosa Intestinal , Intestinos , Microbiota , Ratos , Intoxicação por Frutos do Mar , Testes de Toxicidade Crônica
19.
Ecotoxicology ; 29(4): 398-406, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32300985

RESUMO

Paracetamol (APAP) is a widely used non-steroidal anti-inflammatory drug and has been frequently detected in aquatic environment. However, limited information is provided about the toxic effects and detoxification mechanism of APAP in aquatic invertebrates. In the present study, the change of life traits of Daphnia magna (e.g., body length, growth rate and reproduction) was investigated under the chronic APAP exposure (0-5000 µg/L) for 21 day, and the effects of APAP on the expression of the detoxification- and reproduction-related genes including HR96, CYP360A8, CYP314, MRP4, P-gp, EcR and Vtg in the acute exposure (up to 96 h) were also determined. Results showed that the molting frequency, days to the first brood and days to the first egg production of D. magna were affected under the 50 µg/L concentration of APAP in the chronic exposure test. In the acute test, the transcriptional expression of HR96 was up-regulated under APAP exposure for 24 and 48 h. Similar performances were also observed in the expression of CYP360A8, CYP314, MRP4 and P-gp. However, with exposure time extended to 96 h, the induction of HR96 decreased or even reversed in some cases. It may indicate that the defense system in Daphnia is activated for a short time of exposure or becomes adaptive after longer term of exposure. APAP exposure also affected reproduction-related genes expression, which was related to the exposure time and concentration of APAP. In summary, APAP significantly affected the expression of genes associated with detoxification metabolism and altered some physiological parameters in D. magna.


Assuntos
Acetaminofen/toxicidade , Daphnia/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Inativação Metabólica , Muda/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Testes de Toxicidade Crônica
20.
Ecotoxicology ; 29(5): 514-523, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32277321

RESUMO

Understanding the growth and development of aquatic plants in eutrophic water is of great significance for the selection of potential candidate plant for use in the phytoremediation of eutrophic aquatic ecosystems. The present study aimed to investigate the chronic effects of microcystin-LR (MC-LR) on photosynthesis in the leaves of Typha angustifolia Linn. Photosynthetic activity was stimulated in the leaves following exposure to 4.6 µg L-1 MC-LR for six weeks based on the enhancement of Ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) activity and net photosynthetic rate (PN). However, PN decreased significantly after exposure to 49.1 or 98.3 µg L-1 MC-LR, via non-stomatal limitation by reducing the chlorophyll a and b contents and Rubisco activity. In addition, glycolate oxidase (GO) and serine:glyoxylate aminotransferase (SGAT) activities decreased significantly, indicating that the photorespiration pathway was affected adversely. The intercellular carbon dioxide (Ci) concentration decreased significantly following exposure to 98.3 µg L-1 MC-LR, accompanied with decreases in PN and stomatal conductivity (gs), indicating that stomatal limitation on the photosynthesis system in T. angustifolia L. was observed after exposure to 98.3 µg L-1 MC-LR. Under long-term exposure to MC-LR (49.1-98.3 µg L-1), oxidation stress was severe in the aquatic plant, and non-stomatal limitation or stomatal limitation effects on the photosynthesis system were obvious, resulting in decreases in photosynthesis rates.


Assuntos
Microcistinas/toxicidade , Fotossíntese/efeitos dos fármacos , Typhaceae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Antioxidantes , Clorofila A , Ecossistema , Toxinas Marinhas , Estresse Oxidativo , Folhas de Planta , Ribulose-Bifosfato Carboxilase/metabolismo , Testes de Toxicidade Crônica , Typhaceae/fisiologia , Água
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