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1.
Chemosphere ; 308(Pt 1): 136236, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36057354

RESUMO

Basin land-use interacts with hydrology to deliver chemical contaminants to riverine environments. These chemicals are eventually taken up by aquatic organisms, where they can cause harmful effects. However, knowledge gaps related to the connections between hydrological, chemical, and biological processes currently limit our ability to forecast potential future changes in contaminant concentrations accurately. In this study, concentrations of three pesticide classes (organochlorines, organophosphates, and herbicides) and a standard suite of trace metals were analyzed in the South Saskatchewan River, Canada in 2020 and 2021 in water, sediments, and fishes. Organochlorine pesticides have been banned in Canada since the 1970s, yet there were some detections for methoxychlor and lindane, predominantly in sediment and fish samples, which could be attributed to legacy contamination. Except for malathion and parathion, organophosphate pesticides were scarcely detected in both sampling years in all matrices, and neonicotinoids were below detection in all samples. Conversely, the herbicides 2,4-D and dicamba were detected consistently throughout all locations in water samples for both sampling years. Overall, concentrations were 3 times higher in 2020 when river discharge was ∼2 times higher, suggesting run-off from the surrounding catchment or disturbance of contaminated sediments. Analysis for trace metals revealed that Cu and Zn exceeded sediment quality guidelines in some locations. Mercury concentrations exceeded the guidelines for about 18% of the samples (water and sediment) analyzed. These findings fill gaps in monitoring datasets and highlight key links between hydrology and chemistry that can be further explored in computational models to predict future contaminant trends in freshwater systems.


Assuntos
Herbicidas , Hidrocarbonetos Clorados , Mercúrio , Paration , Praguicidas , Oligoelementos , Poluentes Químicos da Água , Ácido 2,4-Diclorofenoxiacético , Animais , Dicamba , Monitoramento Ambiental , Peixes , Sedimentos Geológicos/química , Herbicidas/análise , Hexaclorocicloexano/análise , Hidrocarbonetos Clorados/análise , Malation , Mercúrio/análise , Metoxicloro/análise , Neonicotinoides/análise , Praguicidas/análise , Rios/química , Oligoelementos/análise , Água/análise , Poluentes Químicos da Água/análise
2.
J Hazard Mater ; 432: 128741, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35349845

RESUMO

Methoxychlor (MXC) is an organopesticide classified as a "Proposed Persistent Organic Pollutant" in the Stockholm Convention, and recent studies revealed that MXC could induce DNA strand breaks, whereas its underlying mechanisms were underinvestigated. Here, we first reported that hydroxymethoxychlor (HPTE), one of MXC's active metabolites, could be oxidized in vivo to form quinone intermediate, which attacked N7 position of 2'-deoxyguanosine to form N7-HPTE-deoxyguanosine (N7-HPTE-dG), followed by depurination to produce N7-HPTE-guanine (N7-HPTE-Gua) in MXC-treated mammalian cells and tissues from mice fed with MXC, employing an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method. We observed a positive correlation between the doses of MXC exposure and the levels of N7-HPTE-Gua and N7-HPTE-dG in cytoplasm and genomic DNA, respectively. Furthermore, after removal of exogenous MXC, the amount of genomic N7-HPTE-dG was significantly decreased during 24 h, while the level of cytoplasmic N7-HPTE-Gua was elevated during first 12 h, indicating the accumulation of the N7-HPTE-Gua in cells. Additionally, for animal experiment, genomic N7-HPTE-dG was observed in livers and cortexes from female C57BL/6 mice fed with MXC, suggesting a potential mechanism of its hepatoxicity and neurotoxicity. Overall, our study provides new understanding about the formation of MXC-induced DNA adducts in mammalian cells and animal models.


Assuntos
Metoxicloro , Poluentes Orgânicos Persistentes , Animais , Adutos de DNA , Desoxiguanosina , Feminino , Mamíferos/metabolismo , Metoxicloro/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Fenóis/toxicidade , Espectrometria de Massas em Tandem
3.
Int J Mol Sci ; 23(5)2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35269923

RESUMO

In this paper, we investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities on ovarian follicles of adult pigs. Piglets were injected with MXC (20 µg/kg body weight) or corn oil (controls) from postnatal Day 1 to Day 10 (n = 5 per group). Then, mRNA expression, protein abundance and immunolocalization of growth and differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), anti-Müllerian hormone (AMH) and cognate receptors (ACVR1, BMPR1A, BMPR1B, TGFBR1, BMPR2, and AMHR2), as well as FSH receptor (FSHR) were examined in preantral and small antral ovarian follicles of sexually mature gilts. The plasma AMH and FSH levels were also assessed. In preantral follicles, neonatal exposure to MXC increased GDF9, BMPR1B, TGFBR1, and BMPR2 mRNAs, while the levels of AMH and BMP15 mRNAs decreased. In addition, MXC also decreased BMP15 and BMPR1B protein abundance. Regarding small antral follicles, neonatal exposure to MXC upregulated mRNAs for BMPR1B, BMPR2, and AMHR2 and downregulated mRNAs for AMH, BMPR1A, and FSHR. MXC decreased the protein abundance of AMH, and all examined receptors in small antral follicles. GDF9 and BMP15 were immunolocalized in oocytes and granulosa cells of preantral follicles of control and treated ovaries. All analyzed receptors were detected in the oocytes and granulosa cells of preantral follicles, and in the granulosa and theca cells of small antral follicles. The exception, however, was FSHR, which was detected only in the granulosa cells of small antral follicles. In addition, MXC decreased the plasma AMH and FSH concentrations. In conclusion, the present study may indicate long-term effects of neonatal MXC exposure on GDF9, BMP15, AMH, and FSH signaling in ovaries of adult pigs. However, the MXC effects varied at different stages of follicular development. It seems that neonatal MXC exposure may result in accelerated initial recruitment of ovarian follicles and impaired cyclic recruitment of antral follicles.


Assuntos
Hormônio Antimülleriano , Metoxicloro , Animais , Hormônio Antimülleriano/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio Foliculoestimulante/farmacologia , Células da Granulosa/metabolismo , Metoxicloro/metabolismo , Metoxicloro/farmacologia , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Proteínas Serina-Treonina Quinases , RNA Mensageiro/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Suínos
4.
Anim Reprod Sci ; 238: 106956, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35231789

RESUMO

Methoxychlor (MXC) is a man-made organochlorine insecticide capable of disrupting endocrine functions due to its mixed steroidal properties (estrogenic, anti-estrogenic and/or anti-androgenic). Retarded follicle development was recently reported in neonatal pigs treated with MXC. The goal of the current study was to better understand the mechanism of MXC action in the ovary of newborn piglets. By employing RNA-Seq we studied the expression of protein coding (mRNA) and long non-coding RNA (lncRNA) transcripts in the ovary of the MXC-treated piglets. Piglets were injected (sc) daily with MXC (100 mg/kg body weight) or corn oil (controls) between postnatal Days 1 and 10 (n = 3 piglets/group). The ovaries excised from 11-day-old piglets were processed for total RNA isolation and subsequent RNA sequencing. Four hundred sixty differentially expressed genes (DEGs) and 143 differentially expressed lncRNAs (DELs) were identified in the ovaries of MXC-treated piglets (P-adjusted < 0.05; abs(log2FC) > 1). Functional enrichment analysis showed that MXC altered the expression of genes associated with intracellular and membrane transport, intra-ovarian signaling as well as cell-cell junction and communication. Moreover, positive and negative correlations determined between the identified DEGs and DELs suggest that some lncRNAs may mediate the MXC action in the ovary. The results support the hypothesis that MXC-induced changes in the expression of genes involved in neonatal ovarian folliculogenesis increase the risk of fertility problems in adults.


Assuntos
Inseticidas , Metoxicloro , Animais , Feminino , Inseticidas/toxicidade , Metoxicloro/metabolismo , Metoxicloro/toxicidade , Folículo Ovariano , Ovário , Suínos/genética , Transcriptoma
5.
Mol Reprod Dev ; 88(3): 238-248, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33655673

RESUMO

This study investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities, on luteal function in pigs. Piglets were injected subcutaneously with MXC (20 µg/kg body weight) or corn oil (control) between postnatal Days 1 and 10 (N = 5/group). Corpora lutea from sexually mature gilts were examined for luteal steroid and prostaglandin concentrations and processed for total RNA isolation and subsequent RNA sequencing. Intra-luteal concentrations of androstenedione and prostaglandin E2 were greater, while that of estrone was lower when compared to control. Fifty-three differentially expressed (DE) microRNAS (miRNAs) (p-adjusted <.05 and log2(fold change) ≥.5) and 359 DE genes (p-adjusted <.05 and log2(fold change) ≥1) were identified in luteal tissue in response to neonatal MXC treatment. MXC was found to affect the expression of genes related to lipogenesis, steroidogenesis, membrane transport, immune response, cell signaling and adhesion. These results suggest an earlier onset of structural luteolysis in pigs caused by MXC actions in neonates. Since negative correlation analysis showed the potential interactions of miRNAs with specific messenger RNAs, we propose that these miRNAs are potential mediators of the long-term MXC effect on the CL function in pigs.


Assuntos
Corpo Lúteo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inseticidas/farmacologia , Metoxicloro/farmacologia , Androstenodiona/metabolismo , Animais , Animais Recém-Nascidos , Corpo Lúteo/metabolismo , Estrona/metabolismo , Feminino , Perfilação da Expressão Gênica , Prostaglandinas/metabolismo , Suínos
6.
Artigo em Inglês | MEDLINE | ID: mdl-33198925

RESUMO

Methoxychlor (MXC), an organo-chlorine insecticide, is a reproductive toxicant in females, causing apoptosis-mediated follicular atresia. To elucidate the potentials of Methoxychlor as a geno-toxicant, granulosa cells of healthy antral follicles, exposed to MXC and antioxidant, N-acetyl-l-cysteine, were studied by the terminal deoxynucleotidyltransferase-dUTP nick end-labelling and single-cell gel electrophoresis (comet) assays. MXC caused DNA fragmentation, as revealed by the increased incidence of dark brown condensed TUNEL positive cells in contrast with lightly brown TUNEL negative cells with maximum TUNEL positive cells were observed in 100 µg/mL MXC treated groups. Quantitatively, maximum geno-toxicity was exhibited at highest MXC treatment with percent tail DNA as 17.87 ± 0.85, 41.16 ± 3.94, and 47.73 ± 3.71 in comparison with control (0.65 ± 0.03, 2.91 ± 0.27, and 7.16 ± 1.39) after 24, 48 and 72 h exposure duration, respectively. MXC treated groups exhibited Type 1-Type 3 comets as compared to Type 0 comets in control groups. Supplementation of NAC led to significant (p < 0.05) decline in geno-toxicity in MXC treated groups with maximum amelioration observed at 5 and 10 mM. Consequently, increased DNA damage attributed to the granulosa cells apoptosis in response to Methoxychlor exposure was significantly combated by NAC supplementation, preventing the geno-toxicity induced cyto-toxicity in GCs.


Assuntos
Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Metoxicloro/toxicidade , Animais , Ensaio Cometa , Feminino , Atresia Folicular/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Cabras , Inseticidas/toxicidade , Folículo Ovariano/citologia , Análise de Célula Única/métodos
7.
Artigo em Inglês | MEDLINE | ID: mdl-33013709

RESUMO

Numerous chemicals derived from human activity are now disseminated in the environment where their exert estrogenic endocrine disrupting effects, and therefore represent major health concerns. The present study explored whether Methoxychlor (MXC), an insecticide with xenoestrogens activities, given during the perinatal period (from gestational day 11 to postnatal day 8) and at an environmentally dose [20 µg/kg (body weight)/day], would affect reproductive physiology and sexual behavior of the offspring in mice. While MXC exposure did not induce any differences in the weight gain of animals from birth to 4 months of age, a clear difference (although in opposite direction according to the sexes) was observed on the anogenital distance between intact and exposed animals. A similar effect was also observed on preputial separation and vaginal opening, which reflects, respectively, in males and females, puberty occurrence. The advanced puberty observed in females was associated with an enhanced expression of kisspeptin cells in the anteroventral periventricular region of the medial preoptic area. Exposure to MXC did not induce in adult females changes in the estrous cycle or in the weight of the female reproductive tract. By contrast, males showed reduced weight of the epididymis and seminiferous vesicles associated with reduced testosterone levels and seminiferous tubule diameter. We also showed that both males and females showed deficits in mate preference tests. As a whole, our results show that MXC impacts reproductive outcomes.


Assuntos
Disruptores Endócrinos/administração & dosagem , Inseticidas/administração & dosagem , Metoxicloro/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Reprodução/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Ciclo Estral/efeitos dos fármacos , Feminino , Kisspeptinas/metabolismo , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Maturidade Sexual/efeitos dos fármacos
8.
J Immunotoxicol ; 17(1): 94-104, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32407153

RESUMO

Currently, assessment of the potential immunotoxicity of a given agent involves a tiered approach for hazard identification and mechanistic studies, including observational studies, evaluation of immune function, and measurement of susceptibility to infectious and neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due to their rapid development, ease of maintenance, and homology to mammalian immune system function and development. Larval zebrafish also are a convenient model to study the innate immune system with no interference from the adaptive immune system. In this study, a respiratory burst assay (RBA) was utilized to measure reactive oxygen species (ROS) production after developmental xenobiotic exposure. Embryos were exposed to non-teratogenic doses of chemicals and at 96 h post-fertilization, the ability to produce ROS was measured. Using the RBA, 12 compounds with varying immune-suppressive properties were screened. Seven compounds neither suppressed nor enhanced the respiratory burst; five reproducibly suppressed global ROS production, but with varying potencies: benzo[a]pyrene, 17ß-estradiol, lead acetate, methoxychlor, and phenanthrene. These five compounds have all previously been reported as immunosuppressive in mammalian innate immunity assays. To evaluate whether the suppression of ROS by these compounds was a result of decreased immune cell numbers, flow cytometry with transgenic zebrafish larvae was used to count the numbers of neutrophils and macrophages after chemical exposure. With this assay, benzo[a]pyrene was found to be the only chemical that induced a change in the number of immune cells by increasing macrophage but not neutrophil numbers. Taken together, this work demonstrates the utility of zebrafish larvae as a vertebrate model for identifying compounds that impact innate immune function at non-teratogenic levels and validates measuring ROS production and phagocyte numbers as metrics for monitoring how xenobiotic exposure alters the innate immune system.


Assuntos
Benzo(a)pireno/efeitos adversos , Testes Imunológicos de Citotoxicidade/métodos , Imunidade Inata/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Explosão Respiratória/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Contagem de Células Sanguíneas , Embrião não Mamífero , Estradiol/efeitos adversos , Estudos de Viabilidade , Ensaios de Triagem em Larga Escala/métodos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Metoxicloro/efeitos adversos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Compostos Organometálicos/efeitos adversos , Fenantrenos/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Explosão Respiratória/imunologia , Peixe-Zebra
9.
Artigo em Inglês | MEDLINE | ID: mdl-32326528

RESUMO

Distribution of pesticide residues in the environment and their transport to surface water bodies is one of the most important environmental challenges. Fate of pesticides in the complex environments, especially in aquatic phases such as lakes and rivers, is governed by the main properties of the contaminants and the environmental properties. In this study, a multimedia mass modeling approach using the Quantitative Water Air Sediment Interaction (QWASI) model was applied to explore the fate of organochlorine pesticide residues of methoxychlor, α-HCH and endosulfan-sulfate in the lake Naivasha (Kenya). The required physicochemical data of the pesticides such as molar mass, vapor pressure, air-water partitioning coefficient (KAW), solubility, and the Henry's law constant were provided as the inputs of the model. The environment data also were collected using field measurements and taken from the literature. The sensitivity analysis of the model was applied using One At a Time (OAT) approach and calibrated using measured pesticide residues by passive sampling method. Finally, the calibrated model was used to estimate the fate and distribution of the pesticide residues in different media of the lake. The result of sensitivity analysis showed that the five most sensitive parameters were KOC, logKow, half-life of the pollutants in water, half-life of the pollutants in sediment, and KAW. The variations of outputs for the three studied pesticide residues against inputs were noticeably different. For example, the range of changes in the concentration of α-HCH residue was between 96% to 102%, while for methoxychlor and endosulfan-sulfate it was between 65% to 125%. The results of calibration demonstrated that the model was calibrated reasonably with the R2 of 0.65 and RMSE of 16.4. It was found that methoxychlor had a mass fraction of almost 70% in water column and almost 30% of mass fraction in the sediment. In contrast, endosulfan-sulfate had highest most fraction in the water column (>99%) and just a negligible percentage in the sediment compartment. α-HCH also had the same situation like endosulfan-sulfate (e.g., 99% and 1% in water and sediment, respectively). Finally, it was concluded that the application of QWASI in combination with passive sampling technique allowed an insight to the fate process of the studied OCPs and helped actual concentration predictions. Therefore, the results of this study can also be used to perform risk assessment and investigate the environmental exposure of pesticide residues.


Assuntos
Endossulfano , Hexaclorocicloexano , Hidrocarbonetos Clorados , Resíduos de Praguicidas , Praguicidas , Poluentes Químicos da Água , Endossulfano/análise , Exposição Ambiental , Monitoramento Ambiental/métodos , Hexaclorocicloexano/análise , Quênia , Lagos , Metoxicloro , Multimídia , Resíduos de Praguicidas/análise , Poluentes Químicos da Água/análise
10.
Environ Toxicol Chem ; 39(1): 220-228, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610606

RESUMO

In the present study, the effects of short-term methoxychlor exposure on the viability, reproduction, and locomotor behavior of adult seminole ramshorn snails (Planorbella duryi) was assessed. To examine impacts on viability and behavior, individuals were exposed to a water control, vehicle control, or 12.5, 50, 100, 250, 500, or 1000 µg/L of methoxychlor for 48 h; and differences in mortality and locomotor behavior assessed using the freely available ToxTrac software. To determine impacts on reproduction, pairs of snails were exposed to a vehicle control and 12.5, 25, 50, 100, and 250 µg/L of methoxychlor for 9 d; and the number of clutches and eggs laid quantified every 24 h. Methoxychlor concentrations in treatments were determined using gas chromatography. Complete mortality was observed in the 500 µg/L and 1000 µg/L treatments after 48 h and in the 250 µg/L treatment after 9 d. Decreases in the number of egg clutches were observed in all treatments, and the number of eggs laid decreased starting in the 25 µg/L treatment. Decreases in average speed, mobile speed, and total distance traveled, as well as a significant increase in frozen events, were also observed. Our results suggest that methoxychlor exposure causes detrimental effects on several nonlethal endpoints in a nonmodel aquatic invertebrate species and that the analysis of locomotor behaviors serves as a reliable, sensitive endpoint for ecotoxicology testing. Environ Toxicol Chem 2019;39:220-228. © 2019 SETAC.


Assuntos
Comportamento Animal/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Metoxicloro/toxicidade , Caramujos/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Reprodução/efeitos dos fármacos , Caramujos/fisiologia , Fatores de Tempo
11.
Toxicol Sci ; 173(1): 19-31, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626307

RESUMO

The present study assessed the potential of a generic physiologically based kinetic (PBK) model to convert in vitro data for estrogenicity to predict the in vivo uterotrophic response in rats for diethylstibestrol (DES), ethinylestradiol (EE2), genistein (GEN), coumestrol (COU), and methoxychlor (MXC). PBK models were developed using a generic approach and in vitro concentration-response data from the MCF-7 proliferation assay and the yeast estrogen screening assay were translated into in vivo dose-response data. Benchmark dose analysis was performed on the predicted data and available in vivo uterotrophic data to evaluate the model predictions. The results reveal that the developed generic PBK model adequate defines the in vivo kinetics of the estrogens. The predicted dose-response data of DES, EE2, GEN, COU, and MXC matched the reported in vivo uterus weight response in a qualitative way, whereas the quantitative comparison was somewhat hampered by the variability in both in vitro and in vivo data. From a safety perspective, the predictions based on the MCF-7 proliferation assay would best guarantee a safe point of departure for further risk assessment although it may be conservative. The current study indicates the feasibility of using a combination of in vitro toxicity data and a generic PBK model to predict the relative in vivo uterotrophic response for estrogenic chemicals.


Assuntos
Bioensaio/métodos , Estrogênios/toxicidade , Útero/fisiologia , Animais , Cumestrol/toxicidade , Dietilestilbestrol/toxicidade , Relação Dose-Resposta a Droga , Estrona , Etinilestradiol/toxicidade , Feminino , Genisteína/toxicidade , Cinética , Metoxicloro/toxicidade , Modelos Biológicos , Fenóis , Ratos , Útero/efeitos dos fármacos
12.
Environ Sci Pollut Res Int ; 26(27): 28328-28340, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31372950

RESUMO

Chiral mesoporous silica (SiO2) with helical structure was synthesized by using anionic surfactants as template. Pre-prepared graphene oxide (GO) was then loaded onto SiO2 to synthesize composite carrier chial-meso-SiO2@GO for the immobilization of laccase. The enzyme activity, thermostability, acid stability, and repeatability of the immobilized enzyme were significantly improved after immobilization. The chial-meso-SiO2@GO-immobilized laccase was then used for the degradation of MXC in aqueous phase. The degradation conditions, including temperature, time, pH, MXC concentration, and the dose of immobilized enzyme for cellulosic hydrolysis, were optimized. The optimum conditions for degradation of methoxychlor were selected as pH 4.5, MXC concentration 30 mg/L, immobilized enzyme dose 0.1 g, the maximum MXC removal of over 85% and the maximum degradation rate of 50.75% were achieved after degradation time of six h at temperature of 45 °C. In addition, the immobilized cellulase was added into the immobilized laccase system to form chial-meso-SiO2@GO-immobilized compound enzyme with the maximum MXC degradation rate of 59.58%, higher than that of 50.75% by immobilized laccase. An assessment was made for the effect of chial-meso-SiO2@GO-immobilized compound enzyme on the degradation of MXC in soil phase. For three contaminated soils with MXC concentration of 25 mg/kg, 50 mg/kg, and 100 mg/kg, the MXC removals were 93.0%, 85.8%, and 65.1%, respectively. According to the GC-MS analyses, it was inferred that chial-meso-SiO2@GO-immobilized compound enzyme had a different degradation route with that of chial-meso-SiO2@GO-immobilized laccase. The hydrolysis by immobilized cellulase might attack at a weak location of the MXC molecule with its free radical OH and ultimately removed three chlorine atoms from MXC molecule, leading to generating small molecular amount of degradation product.


Assuntos
Enzimas Imobilizadas/metabolismo , Grafite/química , Lacase/metabolismo , Metoxicloro/química , Dióxido de Silício/química , Catálise , Poluição Ambiental , Solo , Temperatura , Água/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-30954688

RESUMO

Chinese mitten crab, a featured macrobenthos, has been one of the most important economical aquatic species in China. This study assessed the accumulation of an organochlorine pesticide methoxychlor (MXC) in Chinese mitten crab during exposure to 1 mg/L of MXC. The results showed the residual concentration of MXC in the ovary and hepatopancreas reached 55.07 ±â€¯2.64 ng/g and 34.51 ±â€¯2.35 ng/g, respectively. After exposure, tubular vacuolization of epithelial tissues, condensed egg cells and obvious intervals between egg cell wall and stroma were observed in the hepatopancreas and ovary, respectively. Significant changes of three key metabolic enzymes in hepatopancreas were observed upon exposure to MXC. Compared to the control, acetylcholinesterase level was significantly higher at day 7 (0.15 ±â€¯0.01 vs. 0.06 ±â€¯0.00 U/mgprot); glutathione S-transferase level was elevated at both day 4 (12.01 ±â€¯0.48 vs. 3.20 ±â€¯0.44 U/mgprot) and day 7 (12.84 ±â€¯1.01 vs. 8.22 ±â€¯0.81 U/mgprot); superoxide dismutase was sharply increased at day 4 (21.20 ±â€¯0.24 vs. 3.66 ±â€¯0.60 U/mgprot) but decreased at day 7 (3.74 ±â€¯0.12 vs. 9.44 ±â€¯0.85 U/mgprot). Overall, dissolved MXC accumulated in lipid-rich tissues could cause damages on epithelial cells and egg cells and change metabolic activities of enzymes involved in antioxidative stress and detoxification processes.


Assuntos
Braquiúros/metabolismo , Metoxicloro/metabolismo , Metoxicloro/toxicidade , Animais , Feminino , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Distribuição Tecidual , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
14.
J Vet Med Sci ; 81(4): 541-544, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30773519

RESUMO

The aim of this study is to identify the combined effect of multiple chemicals to the development of allergy. In this study, the effect of prenatal exposure to an organochlorine agent methoxychlor (MXC) and/or an organophosphate agent parathion (PARA) on trimellitic anhydride-induced allergic airway inflammation was examined in mice. Eosinophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly enhanced by MXC + PARA exposure compared to that of the control, MXC, and PARA groups. In the hilar lymph node, only slight increases in B-cell infiltration, as well as IL-6 and IL-9 secretions were observed in MXC + PARA group, and no effect was observed in the individual treatment groups. Our findings imply that prenatal exposure to some combinations of multiple chemicals may exacerbate the allergic inflammatory responses including eosinophils and cytokine production.


Assuntos
Imunossupressores/toxicidade , Metoxicloro/toxicidade , Paration/toxicidade , Efeitos Tardios da Exposição Pré-Natal/imunologia , Hipersensibilidade Respiratória/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas , Sinergismo Farmacológico , Eosinófilos , Feminino , Linfonodos/citologia , Linfonodos/imunologia , Metoxicloro/administração & dosagem , Camundongos Endogâmicos BALB C , Paration/administração & dosagem , Anidridos Ftálicos/imunologia , Gravidez , Hipersensibilidade Respiratória/imunologia
15.
Neurosci Lett ; 684: 169-174, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30107201

RESUMO

Methoxychlor is primarily used as an insecticide and it is widely present in the environment. The objective of the present study was to investigate the direct effects of methoxychlor and its metabolite hydroxychlor (HPTE) on rat neurosteroidogenic 3α-hydroxysteroid dehydrogenase (AKR1C14) and retinol dehydrogenase 2 (RDH2) activities. Rat AKR1C14 and RDH2 were cloned and expressed in COS-1 cells, and the effects of methoxychlor and HPTE on these enzymes were measured. HPTE was more potent to inhibit AKR1C14 and RDH2 activities than methoxychlor, with IC50 values of 2.602 ± 0.057 µM and 20.473 ± 0.049 µM, respectively, while those of methoxychlor were over 100 µM. HPTE competitively inhibited AKR1C14 and RDH2 when steroid substrates were used, while it showed a mode of mixed inhibition on these enzymes when NADPH/NAD+ were used. We elucidated the binding mode of methoxychlor and HPTE to the crystal structure of AKR1C14 by molecular docking and found that HPTE had higher affinity with the enzyme than methoxychlor. In conclusion, HPTE is more potent than methoxychlor to inhibit both AKR1C14 and RDH2.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Inibidores de 5-alfa Redutase/farmacologia , Oxirredutases do Álcool/antagonistas & inibidores , Oxirredutases do Álcool/metabolismo , Metoxicloro/farmacologia , Fenóis/farmacologia , Animais , Células COS , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Inseticidas/farmacologia , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína , Ratos
16.
J Immunotoxicol ; 15(1): 104-118, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29973080

RESUMO

Endocrine-disrupting chemicals (EDC) are widespread in the built and natural environments. Heightened public awareness of their potential danger has led to concern about whether EDC and their metabolites have significant negative biological effects. Studies have shown that EDC like DDT and other organochlorine pesticides, such as methoxychlor (MXC), have adverse effects on immune cells, but no studies have addressed the impact of HPTE, the primary metabolite of MXC. To elucidate the presence and significance of HPTE adverse effects, this study explored the impact of HPTE on a critical window and component of immune system development, embryonic T-cell development. Lesions at this phase of development can lead to lifelong immune dysfunction and increased incidence of immune disease, such as autoimmunity. Embry-onic thymocytes (GD 16-18) from C57BL/6 mice were subjected to an in vitro differentiation culture that mimicked early steps in thymocyte development in the presence of 0.005, 0.05, 0.5, 5, or 50 µM HPTE, or a model endocrine disruptor, DES. The results indicated that compared to the vehicle control, HPTE- and DES-induced death of thymocytes. Annexin-V staining and Caspase 8, markers of programed cell death, revealed that the loss of cells was due at least in part to induction of apoptosis. Moreover, HPTE-induced cell death not only resulted in selective loss of double positive thymocytes, but also loss of developing CD4 intermediate cells (post-double positive partially differentiated thymocyte population). Phenotypic analysis of thymocyte maturation (T-cell receptor, TCR) and TCR ligation (CD5) surface markers revealed that surviving embryonic thymocytes expressed low levels of both. Taken together these data demonstrate that immature embryonic thymocytes are sensitive to HPTE exposure and that HPTE exposure targets thymocyte populations undergoing critical differentiation steps. These findings suggest HPTE may play a pivotal role in MXC exposure-induced immune dysfunction.


Assuntos
Disruptores Endócrinos/toxicidade , Metoxicloro/toxicidade , Praguicidas/toxicidade , Fenóis/toxicidade , Linfócitos T/fisiologia , Timócitos/fisiologia , Animais , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Feminino , Desenvolvimento Fetal , Feto , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
Fish Physiol Biochem ; 44(6): 1421-1434, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29520649

RESUMO

The organochlorine pesticides aldrin (0.14 µg/L) and methoxychlor (0.23 µg/L) were both present in the Albasini Dam, Limpopo Province, South Africa, during a field survey in 2014. The use of aldrin has been banned in the USA since 1987 and restricted in South Africa since 1992. The use of methoxychlor, however, remains undefined with little information available about its registration in South Africa despite being banned in Europe (2002) and USA (2003). The aim of this study was to determine the potential effects of environmentally relevant concentrations of aldrin and methoxychlor on the reproductive system of male catfish, Clarias gariepinus. Males were exposed for 96 h to the two pesticides under controlled laboratory conditions. Following exposure, each fish was weighed and measured, and a necropsy performed to determine any macroscopic abnormalities and the general health of the fish. The fish were killed and dissected and the testes removed, weighed and measured to determine the gonadosomatic index (GSI). The right testis of each fish was sectioned for histopathological assessment and to calculate the testes index (IT). The left testis was used for computer-assisted sperm analysis (CASA). The histopathological assessment of the testes showed histopathological changes such as of melano-macrophage centres (MMCs) and vacuolation of spermatogonia and spermatocytes. However, the classification of these changes indicated that the testes tissue structure was normal with slight histological changes. No statistically significant differences (p > 0.05) were found in the CASA parameters between exposure groups. The results of this study showed that the environmentally relevant concentrations of aldrin and methoxychlor did not have a negative effect on the motility of the mature sperm, but adverse effects were noted in the early stages of spermatogenesis, indicating possible effects over longer exposure periods.


Assuntos
Aldrina/toxicidade , Peixes-Gato/fisiologia , Metoxicloro/toxicidade , Espermatócitos/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Monitoramento Ambiental , Inseticidas/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Espermatócitos/citologia , Espermatogônias/citologia , Poluentes Químicos da Água/toxicidade
18.
J Nanosci Nanotechnol ; 18(4): 2971-2978, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442982

RESUMO

In the present work, three differently shaped mesoporous silica nanoparticles, spherical nano-SiO2, tubular mesoporous SiO2 and vesicle-like mesoporous SiO2 (VSL), were prepared and used to immobilize Horse radish peroxidase (HRP), and their enzyme's activity was also evaluated. It was found that the VSL immobilized HRP displayed higher specific activity than free enzyme and other two differently shaped silica immobilized HRP. After immobilization, the thermal stability, pH tolerance resistance and storage stability on vesicle-like SiO2 were studied as well. In addition, the kinetic constants Km and Vmax for HRP were significantly altered by immobilization. The affinity for HRP towards its substrate increased (with decreasing Km), leading to enhanced catalytic efficiency (with increased Vmax). Moreover, the reusability for degradation of methoxychlor (MXC) by VSL immobilized enzyme was studied and its degradation products were detected by GC-MS and NMR analysis.


Assuntos
Estabilidade Enzimática , Peroxidase do Rábano Silvestre/metabolismo , Nanoestruturas , Dióxido de Silício/química , Enzimas Imobilizadas , Metoxicloro , Temperatura
19.
Theriogenology ; 113: 19-26, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29452853

RESUMO

The objective of the study was to examine the effects of androgen and estrogen agonists or antagonists on the follicle formation, ovarian cell proliferation and apoptosis as well as plasma steroid concentration in neonatal pigs. Piglets were injected with testosterone propionate (TP, 20 mg/kg bw), flutamide (FLU, 50 mg/kg bw), 4-tert-octylphenol (OP, 100 mg/kg bw), ICI 182,780 (ICI, 400 µg/kg bw), methoxychlor (MXC, 100 mg/kg bw) or corn oil (CTR, controls) between postnatal Days 1 and 10 (n = 4/group). Heart blood was collected and ovaries were excised from the 11-day-old piglets. The lower percentage of oocytes within an egg nest and higher ovarian expression of active caspase 3 were found in TP (androgen excess) piglets compared to controls. FLU-induced androgen deficiency decreased the percentage of primordial follicles, increased that of early primary follicles and diminished ovarian cell proliferation. OP-induced estrogen action increased the percentage of primordial and developing follicles as well as cell proliferation. ICI-induced estrogen deficiency decreased the percentage of transitional follicles and ovarian cell proliferation, while increased the percentage of primordial follicles and the abundance of active caspase 3. Treatment with MXC, exhibiting estrogenic, antiestrogenic, and antiandrogenic activities, declined the percentage of developing follicles and cell proliferation. Moreover, the investigated compounds differentially affected plasma steroid level. In conclusion, the present study demonstrated clear effects of TP and FLU during the earliest stages of folliculogenesis in pigs (nest breakdown and follicle assembly), whereas OP and ICI influenced also the subsequent stages of follicle initial recruitment and growth. Therefore, the androgen and estrogen seems to be important for the follicle assembly and follicle growth in neonatal porcine ovaries.


Assuntos
Androgênios/farmacologia , Flutamida/farmacologia , Folículo Ovariano/efeitos dos fármacos , Fenóis/farmacologia , Suínos , Propionato de Testosterona/farmacologia , Antagonistas de Androgênios/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas do Receptor de Estrogênio/farmacologia , Feminino , Fulvestranto , Células da Granulosa , Inseticidas/farmacologia , Metoxicloro/farmacologia
20.
Biotech Histochem ; 92(3): 230-242, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28409689

RESUMO

Follicular development and other ovarian functions are regulated by growth factors that can be affected by exogenous agents. Methoxychlor (MXC) is an organochloride pesticide that causes female infertility. We investigated how MXC affects the distribution of developing ovarian follicles in adult rats after treatment between embryonic day (E) 18 and postnatal day (PND) 7. We also measured insulin-like growth factor-I (IGF-I) and its receptor, IGF-IR, expressions in ovarian follicles and investigated whether MXC changed the levels of IGF-I and IGF-IR in the ovary. Using immunohistochemical (IHC) staining, we detected IGF-I expression in oocytes and granulosa cells of the follicles, luteal cells, interstitial cells, theca externa and theca interna, and the smooth muscle of ovarian vessels. IGF-IR was co-localized with IGF-I in the ovary except for the theca externa. IGF-I expression was decreased in granulosa cells of preantral and antral follicles after treatment with MXC compared to granulosa cells of preantral and antral follicles of the control group. We also observed that oocytes of secondary follicles and granulosa cells of secondary and preantral follicles of the MXC treated groups showed increased IGF-IR expression compared to oocytes of secondary follicles and granulosa cells of secondary and preantral follicles of the control group. We also detected more secondary and preantral follicles, and fewer primordial and antral follicles after MXC administration compared to controls. Therefore, the IGF signaling pathway may participate in MXC induced ovary dysfunction and female infertility.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Metoxicloro/toxicidade , Ovário/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Poluentes Ambientais/toxicidade , Feminino , Imuno-Histoquímica , Ratos , Ratos Wistar
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