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1.
Pestic Biochem Physiol ; 174: 104797, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33838701

RESUMO

Tebuconazole (TEB) is a common triazole fungicide that has been widely used for the control of plant pathogenic fungi, suggesting that mammal exposure occurs regularly. Several studies demonstrated that TEB exposure has been linked to a variety of toxic effects, including neurotoxicity, immunotoxicity, reprotoxicity and carcinogenicity. However, there is a few available data regarding the molecular mechanism involved in TEB-induced toxicity. The current study was undertaken to investigate the toxic effects of TEB in HCT116 cells. Our results showed that TEB caused cytotoxicity by inhibiting cell viability as assessed by the MTT assay. Furthermore, we have demonstrated that TEB induced a significant increase in the reactive oxygen species (ROS) production leading to the induction of lipid peroxidation and DNA fragmentation and increased superoxide dismutase (SOD) and catalase (CAT) activities. Moreover, TEB exposure induced mitochondrial membrane potential loss and caspase-9/-3 activation. Treatment with general caspases inhibitor (Z-VAD-fmk) significantly prevented the TEB-induced cell death, indicating that TEB induced caspases-dependent cell death. These findings suggest the involvement of oxidative stress and apoptosis in TEB-induced toxicity in HCT116.


Assuntos
Dano ao DNA , Triazóis , Animais , Apoptose , Células HCT116 , Humanos , Estresse Oxidativo , Espécies Reativas de Oxigênio , Triazóis/toxicidade
2.
Ecotoxicol Environ Saf ; 214: 112105, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33690003

RESUMO

Eusocial Apis mellifera colonies depend on queen longevity and brood viability to survive, as the queen is the sole reproductive individual and the maturing brood replenishes the shorter-lived worker bees. Production of many crops rely on both pesticides and bee pollination to improve crop quantity and quality, yet sublethal impacts of this pesticide exposure is often poorly understood. We investigated the resiliency of queens and their brood after one month of sublethal exposure to field relevant doses of pesticides that mimic exposure during commercial pollination contracts. We exposed full size colonies to pollen contaminated with field-relevant doses of the fungicides (chlorothalonil and propicanizole), insecticides (chlorypyrifos and fenpropathrin) or both, noting a significant reduction in pollen consumption in colonies exposed to fungicides compared to control. While we found no difference in the total amount of pollen collected per colony, a higher proportion of pollen to non-pollen foragers was detected in all pesticide exposed colonies. After ceasing treatments, we measured brood development, discovering a significant increase in brood loss and/or cannibalism across all pesticide exposed groups. Sublethal pesticide exposure in general was linked to reduced production of replacement workers and a change in protein acquisition (pollen vs. non-pollen foraging). Fungicide exposure also resulted in increased loss of the reproductive queen.


Assuntos
Abelhas/efeitos dos fármacos , Clorpirifos/toxicidade , Fungicidas Industriais/toxicidade , Inseticidas/toxicidade , Nitrilos/toxicidade , Pólen , Piretrinas/toxicidade , Triazóis/toxicidade , Animais , Abelhas/fisiologia , Feminino , Polinização , Reprodução/efeitos dos fármacos
3.
Ecotoxicol Environ Saf ; 213: 111985, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33578099

RESUMO

The rampant use of pesticides can cause serious environmental problems. They can be contaminating surface water and groundwater, affecting the surrounding micro and macro biota. In this sense, this work aimed to evaluate the effects of a tebuconazole-based fungicide through endpoints accessed in Lactuca sativa bioassays. Germinated-seeds with roots upon 2 mm were treated with a fungicide containing Tebuconazole (TBZ) as active compound. The final concentration of TBZ in the tested solutions were 0.025 (C1); 0.05 (C2); 0.1 (C3); 0.2 (C4) and 0.4 g/L (C5). L. sativa roots were exposed for 24 h to these solutions and Petri dishes containing the treated seeds were kept in incubation chamber at 24 °C. Two positive controls (PC,) the herbicide trifluralin (0.84 mg/L) and Methanesulfonate (4 ×10-4 mol/L), were applied. Distilled water was negative control (NC). The following endpoints were analyzed: root growth (RG), cytogenotoxic potential by cell cycle analysis, induction of DNA damage through TUNEL and comet assays. The obtained data were submitted to one-way variance analysis (ANOVA) and then to Tukey or Kruskal Wallis (P < 0.05) tests. The concentrations (C1, C2, C4 and C5) affected negatively the RG of L. sativa, in comparison with the NC. The mitotic index was reduced by 25% from NC to C1 and in the rest of treatments it did not present significant modifications. However, from C3 to C5 great amount of chromosome alterations were observed, in comparison with the NC. TBZ-based fungicide also induced DNA fragmentation as measured by TUNEL and comet assays. Thus, TBZ-based fungicide in some concentrations can have phytotoxic, cytotoxic and genotoxic effects in roots and meristematic cells of L. sativa.


Assuntos
Fungicidas Industriais/toxicidade , Alface/fisiologia , Triazóis/toxicidade , Bioensaio , Aberrações Cromossômicas , Ensaio Cometa , Dano ao DNA , Germinação/efeitos dos fármacos , Herbicidas/toxicidade , Meristema/efeitos dos fármacos , Índice Mitótico , Raízes de Plantas/efeitos dos fármacos , Sementes/efeitos dos fármacos , Toxicogenética
4.
Toxicol Lett ; 342: 73-84, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609687

RESUMO

Trovafloxacin (TVX) is associated with idiosyncratic drug-induced liver injury (iDILI) and inflammation-mediated hepatotoxicity. However, the inflammatory stress-regulated mechanisms in iDILI remain unclear. Herein, we elucidated the novel role of tumor-necrosis factor alpha (TNFα), an inflammatory stress factor, in TVX-induced in vitro hepatotoxicity and synergistic toxicity. TVX specifically induced synergistic toxicity in HepG2 cells with TNFα, which inhibits autophagy. TVX-treated HepG2 cells induced protective autophagy by inhibiting the expression of mTOR signaling proteins, while ATG5 knockdown in HepG2 cells, responsible for the impairment of autophagy, enhanced TVX-induced toxicity due to the increase in cytochrome C release and JNK pathway activation. Interestingly, the expression of mTOR signal proteins, which were suppressed by TVX, disrupted the negative feedback of the PI3K/AKT pathway and TNFα rebounded p70S6K phosphorylation. Co-treatment with TVX and TNFα inhibited protective autophagy by maintaining p70S6K activity, which enhanced TVX-induced cytotoxicity. Phosphorylation of p70S6K was inhibited by siRNA knockdown and rapamycin to restore TNFα-inhibited autophagy, which prevented the synergistic effect on TVX-induced cytotoxicity. These results indicate that TVX activates protective autophagy in HepG2 cells exposed to toxicity and an imbalance in negative feedback regulation of autophagy by TNFα synergistically enhanced the toxicity. The finding from this study may contribute to a better understanding of the mechanisms underlying iDILI associated with inflammatory stress.


Assuntos
Autofagia/efeitos dos fármacos , Fluoroquinolonas/toxicidade , Hepatócitos/efeitos dos fármacos , Naftiridinas/toxicidade , Fator de Necrose Tumoral alfa/farmacologia , Antimaláricos/toxicidade , Sobrevivência Celular , Cloroquina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Levofloxacino/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Piperazinas/toxicidade , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Inibidores da Recaptação de Serotonina e Norepinefrina/toxicidade , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Triazóis/toxicidade
5.
Environ Pollut ; 271: 116292, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33388683

RESUMO

Drilled seeds are an important food resource for many farmland birds but may pose a serious risk when treated with pesticides. Most compounds currently used as seed treatment in the EU have low acute toxicity but may still affect birds in a sub-chronic or chronic way, especially considering that the sowing season lasts several weeks or months, resulting in a long exposure period for birds. Tebuconazole is a triazole fungicide widely used in agriculture but its toxicity to birds remains largely unknown. Our aim was to test if a realistic scenario of exposure to tebuconazole treated seeds affected the survival and subsequent reproduction of the red-legged partridge (Alectoris rufa). We fed captive partridges with wheat seeds treated with 0%, 20% or 100% of tebuconazole application rate during 25 days in late winter (i.e. tebuconazole dietary doses were approximately 0.2 and 1.1 mg/kg bw/day). We studied treatment effects on the physiology (i.e. body weight, biochemistry, immunology, oxidative stress, coloration) and reproduction of partridges. Exposed birds did not reduce food consumption but presented reduced plasmatic concentrations of lipids (triglycerides at both exposure doses, cholesterol at high dose) and proteins (high dose). The coloration of the eye ring was also reduced in the low dose group. Exposure ended 60 days before the first egg was laid, but still affected reproductive output: hatching rate was reduced by 23% and brood size was 1.5 times smaller in the high dose group compared with controls. No significant reproductive effects were found in the low dose group. Our results point to the need to study the potential endocrine disruption mechanism of this fungicide with lagged effects on reproduction. Risk assessments for tebuconazole use as seed treatment should be revised in light of these reported effects on bird reproduction.


Assuntos
Fungicidas Industriais , Melhoramento Vegetal , Animais , Fungicidas Industriais/toxicidade , Reprodução , Sementes , Triazóis/toxicidade
6.
Ecotoxicol Environ Saf ; 211: 111894, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33472108

RESUMO

Enantiomers of chiral fungicides usually display different toxic effects on nontarget organisms in the surrounding environment, although there are rare reports on the enantioselective toxicity of metconazole (MEZ) to aquatic organisms, such as Microcystis flos-aquae (M. flos-aquae). To explore the enantioselective toxicity of MEZ in algae, the impact of various concentrations (0.001, 0.003, 0.01, 0.03 and 0.1 mg/L) of MEZ on M. flos-aquae over 8 days was investigated. Significant differences were observed between the four enantiomers in chlorophyll a (Chl a) contents, carotenoids, photochemical efficiency (Fv/Fm), rapid light-response curves (RLCs), utilization efficiency of light energy (α) and protein contents during treatment time. MEZ can enantioselectively stimulate the chlorophyll fluorescence parameters (RLCs, Fv/Fm and α) and carotenoid and Chl a contents of M. flos-aquae, especially at low concentrations (0.001 or 0.003 mg/L). At high concentrations of 0.03 or 0.1 mg/L, the chlorophyll fluorescence parameters (RLCs, Fv/Fm and α), protein and Chl a contents of M. flos-aquae exposed to cis-enantiomers were lower than those of M. flos-aquae exposed to trans-enantiomers. These observations indicated that the enantiomers of MEZ pose different toxicities to M. flos-aquae, with the cis-enantiomers more toxic than the trans-enantiomers. These results are beneficial for understanding the enantioselective effects of MEZ enantiomers on nontarget organisms and helpful for evaluating their eco-environment risk.


Assuntos
Fungicidas Industriais/toxicidade , Microcystis/fisiologia , Fotossíntese/efeitos dos fármacos , Triazóis/toxicidade , Clorofila A , Microcystis/efeitos dos fármacos , Estereoisomerismo
7.
Chemosphere ; 262: 127793, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32799142

RESUMO

Currently, few studies have investigated the joint toxicity mechanism of azole fungicides at different exposure times and mixed at the relevant environmental concentrations. In this study, three common azole fungicides, namely, myclobutanil (MYC), propiconazole (PRO), and tebuconazole (TCZ), were used in studying the toxic mechanisms of a single substance and its ternary mixture exposed to ambient concentrations of Chlorella pyrenoidosa. Superoxide dismutase (SOD), catalase (CAT), chlorophyll a (Chla), and total protein (TP), were used as physiological indexes. Results showed that three azole fungicides and ternary mixture presented obvious time-dependent toxicities at high concentrations. MYC induced a hormetic effect on algal growth, whereas PRO and TCZ inhibit algal growth in the entire range of the tested concentrations. The toxicities of the three azole fungicides at 7 days followed the order PRO > TCZ > MYC. Three azole fungicides and their ternary mixture induced different levels of SOD and CAT activities in algae at high concentrations. The ternary mixture showed additive effects after 4 and 7 days exposure, but no effect was observed at actual environmental concentrations. The toxic mechanisms may be related to the continuous accumulation of reactive oxygen species, which not only affected protein structures and compositions but also damaged thylakoid membranes, hindered the synthesis of proteins and chlorophyll a, and eventually inhibited algal growth. These findings increase the understanding of the ecotoxicity of azole fungicides and use of azole fungicides in agricultural production.


Assuntos
Antioxidantes/metabolismo , Azóis/toxicidade , Chlorella/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Catalase/metabolismo , Chlorella/enzimologia , Chlorella/crescimento & desenvolvimento , Clorofila A/metabolismo , Relação Dose-Resposta a Droga , Nitrilos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Triazóis/toxicidade
8.
Chemosphere ; 262: 127792, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805656

RESUMO

Tebuconazole is a triazole fungicide, used in agriculture to treat phytopathogenic fungi, and as a biocide, has been reported to be related to reproductive and developmental toxicity. The purpose of this study was to investigate the effect of tebuconazole exposure on rat fetal Leydig cells and fetal testis during pregnancy. Pregnant Sprague-Dawley rats were randomly divided into 4 groups, daily gavaged with corn oil (as a control), 25, 50, and 100 mg/kg body weight tebuconazole for 10 days (from the 12th day of pregnancy). Tebuconazole increased fetal serum testosterone and progesterone levels at a dose of 100 mg/kg. Exposure to 100 mg/kg tebuconazole significantly caused an increase in the number of fetal Leydig cells per testis without inducing cell aggregation. Tebuconazole up-regulated the expression of Star, Cyp11a1, Hsd17b3, and Fshr and their proteins. Further investigation found that tebuconazole caused increased phosphorylation of AKT1, ERK1/2, and mTOR, the level of BCL2, as well as the decrease of Beclin1, LC3B, and BAX, which may contribute to the fetal Leydig cell autophagy and proliferation. In conclusion, in utero exposure of tebuconazole causes the proliferation of fetal Leydig cells.


Assuntos
Fungicidas Industriais/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Reprodução/efeitos dos fármacos , Triazóis/toxicidade , Animais , Feminino , Células Intersticiais do Testículo/metabolismo , Masculino , Fosfoproteínas/genética , Fosforilação , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Testículo/efeitos dos fármacos , Testículo/embriologia , Testículo/patologia , Testosterona/sangue , Regulação para Cima
9.
Sci Total Environ ; 753: 141940, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32890874

RESUMO

Environmental pollutants and especially endocrine disrupting chemicals (EDCs) are implicated as one of the drivers of the amphibian declines. To advance the understanding of the risks of EDCs to amphibians, methods to determine endocrine-linked adverse effects are needed. The aims were to 1) develop a partial life-cycle assay with the model frog Xenopus tropicalis to determine endocrine perturbation and adverse developmental effects, and 2) determine effects of propiconazole in this assay. Propiconazole is a pesticide with multiple endocrine modes of action in vitro. Its potential endocrine activity and adverse effects in amphibians remain to be elucidated. Tadpoles were exposed to 0, 33 and 384 µg propiconazole/L during critical developmental windows until completed metamorphosis. At metamorphosis, a sub-sample of animals was analysed for endpoints for disruption of estrogen/androgen (sex ratio, brain aromatase activity) and thyroid pathways (time to metamorphosis). The remaining individuals were kept unexposed for 2 months post-metamorphosis to analyze effects on sexual development including gonadal and Müllerian duct maturity and gametogenesis. At metamorphosis, brain aromatase activity was significantly increased in the high-dose group compared to control. In both propiconazole groups, an increased proportion of individuals reached metamorphosis faster than the mean time for controls, suggesting a stimulatory effect on the thyroid system. At 2 months post-metamorphosis, testis size, sperm and Müllerian duct maturity were reduced in the low-dose males, and the liver somatic index in males was increased in both propiconazole groups, compared with controls. In conclusion, our results show that propiconazole exposure caused endocrine perturbations and subsequent hepatic and reproductive effects evident at puberty, indicating persistent disruption of metabolism and male reproductive function. Our findings advance the development of methodology to determine endocrine and adverse effects of EDCs. Moreover, they increase the understanding of endocrine perturbations and consequent risk of adverse effects of azoles in amphibians.


Assuntos
Disruptores Endócrinos , Triazóis , Animais , Disruptores Endócrinos/toxicidade , Humanos , Larva , Masculino , Metamorfose Biológica , Reprodução , Triazóis/toxicidade , Xenopus
10.
Ecotoxicol Environ Saf ; 207: 111236, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32911182

RESUMO

The fungicides epoxiconazole and pyraclostrobin have been widely used to control wheat fusarium head blight. This study was designed to investigate the dissipation behaviors in different climate regions and provide data for the modification of maximum residue limits of the two fungicides. Wheat samples were collected from field sites in twelve different regions, China and analyzed with an HPLC-MS/MS method for simultaneous detection of epoxiconazole and pyraclostrobin in wheat. The average recoveries of epoxiconazole and pyraclostrobin in wheat matrix were 87-112% and 85-102%, respectively, with the relative standard deviations ≤8.1%. The limits of quantification of epoxiconazole and pyraclostrobin in grain and straw were both 0.01 mg/kg. The dissipations of epoxiconazole and pyraclostrobin followed first-order kinetics, with the half-lives of 10.3 days and 7.6 days, respectively. The terminal residues of epoxiconazole and pyraclostrobin in grain were below 0.034 and 0.028 mg/kg, separately, both lower than the maximum residue limits recommended by China. Based on Chinese dietary pattern and terminal residue distributions, the risk quotients of epoxiconazole and pyraclostrobin were 13.9% and 65.9%, respectively, revealing the evaluated wheat exhibited an acceptably low dietary risk to consumers.


Assuntos
Compostos de Epóxi/análise , Fungicidas Industriais/análise , Resíduos de Praguicidas/análise , Estrobilurinas/análise , Triazóis/análise , Triticum/fisiologia , China , Cromatografia Líquida de Alta Pressão , Dieta , Exposição Dietética/estatística & dados numéricos , Compostos de Epóxi/toxicidade , Fungicidas Industriais/toxicidade , Resíduos de Praguicidas/toxicidade , Medição de Risco , Estrobilurinas/toxicidade , Espectrometria de Massas em Tandem/métodos , Triazóis/toxicidade , Triticum/efeitos dos fármacos
11.
Environ Pollut ; 270: 116269, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33338958

RESUMO

The enantioselective toxic effect and environmental behavior of chiral pesticides have attracted increasing research attention. In this study, the enantioselective toxicity and residues of hexaconazole (HEX) in earthworms (Eisenia fetida) were investigated. In the present study, significant enantioselective degradation characteristics were observed in artificial soil with the R-enantiomer preferentially degrading (p < 0.05); however, no significant enantioselective bioaccumulation was observed in the earthworms (p > 0.05). The acute toxicity of S-(+)-HEX was higher than that of R-(-)-HEX in earthworms, with 48-h LC50 values of 8.62 and 22.35 µg/cm2, respectively. At 25 mg/kg, enantiospecific induction of oxidative stress was observed in earthworms; moreover, S-(+)-HEX had a greater influence on the contents of malonaldehyde, cytochrome P450, and 8-hydroxy-2-deoxyguanosine than R-(-)-HEX. These results were consistent with those of the enrichment analysis of differentially expressed genes. The transcriptome sequencing results showed that S-(+)-HEX had a more significant influence on steroid biosynthesis, arachidonic acid metabolism, and cell cycle processes than R-(-)-HEX, leading to abnormal biological function activities. These results indicate that S-(+)-HEX may pose a higher risk to soil organisms than R-(-)-HEX. This study suggests that the environmental risk of chiral pesticides to nontarget organisms should be assessed at the enantiomeric level.


Assuntos
Fungicidas Industriais , Oligoquetos , Poluentes do Solo , Animais , Fungicidas Industriais/toxicidade , Solo , Poluentes do Solo/toxicidade , Estereoisomerismo , Triazóis/análise , Triazóis/toxicidade
12.
Chemosphere ; 261: 128054, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33113645

RESUMO

Triazophos (TAP), methamidophos (MAP) and carbofuran (CF) pesticides are highly toxic, soluble and absorbable. Efficient co-degradation of multi-pesticides is rare reported. The objectives of this study were to investigate TAP, MAP and CF co-degradative ability of Enterobacter sp. Z1 and study the degradation mechanisms. Strain Z1 was shown to efficiently co-degrade TAP, MAP and CF when they were used as primary carbon sources. The degradation occurred over a wide range of temperatures, pH values and pesticide concentrations and followed first-order kinetics. Under the optimum conditions (37 °C, pH 7 and 100 mg/L of each pesticide), the degradation efficiencies were 100%, 100%, and 95.3% for TAP, MAP and CF, respectively. In addition, strain Z1 could simultaneously degrade TAP, MAP, CF and total nitrogen in wastewater in a batch bioreactor, with high removal efficiencies of 98.3%, 100%, 98.7% and 100%, respectively. Genomics, proteomics, qRT-PCR and gene overexpression analyses revealed that the degradation mechanisms involved the activities of multiple proteins, among which, organophosphorus hydrolase (Oph) and 3-hydroxyacyl-CoA dehydrogenase (PaaC) are primarily responsible for TAP and MAP degradation, while carbofuran hydrolase (Mcd) and amidohydrolase (RamA) primarily degrade CF. Among these enzymes, PaaC and RamA are newly identified pesticide-degrading enzymes. Toxicity assays of strain Z1 using reporter recombinase gene (recA) and zebrafish showed that there was no accumulation of toxic metabolites during the degradation process. Biosafety test using zebrafish showed that the strain was nontoxic toward zebrafish. Strain Z1 provides a good purification effect for pesticides-containing wastewater and novel microbial pesticide-degrading mechanisms were discovered.


Assuntos
Reatores Biológicos/microbiologia , Enterobacter/metabolismo , Praguicidas , Águas Residuárias/química , Poluentes Químicos da Água , Purificação da Água/métodos , Biodegradação Ambiental , Carbofurano/análise , Carbofurano/toxicidade , Contenção de Riscos Biológicos , Enterobacter/efeitos dos fármacos , Hidrolases/metabolismo , Organotiofosfatos/análise , Organotiofosfatos/toxicidade , Compostos Organotiofosforados/análise , Compostos Organotiofosforados/toxicidade , Praguicidas/análise , Praguicidas/toxicidade , Triazóis/análise , Triazóis/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
13.
Ecotoxicol Environ Saf ; 203: 111013, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888588

RESUMO

Multiple pesticides originating from plant protection treatments and the treatment of pests infecting honey bees are frequently detected in beehive matrices. Therefore, winter honey bees, which have a long life span, could be exposed to these pesticides for longer periods than summer honey bees. In this study, winter honey bees were exposed through food to the insecticide imidacloprid, the fungicide difenoconazole and the herbicide glyphosate, alone or in binary and ternary mixtures, at environmental concentrations (0 (controls), 0.1, 1 and 10 µg/L) for 20 days. The survival of the honey bees was significantly reduced after exposure to these 3 pesticides individually and in combination. Overall, the combinations had a higher impact than the pesticides alone with a maximum mortality of 52.9% after 20 days of exposure to the insecticide-fungicide binary mixture at 1 µg/L. The analyses of the surviving bees showed that these different pesticide combinations had a systemic global impact on the physiological state of the honey bees, as revealed by the modulation of head, midgut and abdomen glutathione-S-transferase, head acetylcholinesterase, abdomen glucose-6-phosphate dehydrogenase and midgut alkaline phosphatase, which are involved in the detoxification of xenobiotics, the nervous system, defenses against oxidative stress, metabolism and immunity, respectively. These results demonstrate the importance of studying the effects of chemical cocktails based on low realistic exposure levels and developing long-term tests to reveal possible lethal and adverse sublethal interactions in honey bees and other insect pollinators.


Assuntos
Abelhas/fisiologia , Fungicidas Industriais/toxicidade , Herbicidas/toxicidade , Inseticidas/toxicidade , Praguicidas/toxicidade , Animais , Dioxolanos/toxicidade , Sinergismo Farmacológico , Glicina/análogos & derivados , Glicina/toxicidade , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Polinização/efeitos dos fármacos , Triazóis/toxicidade
14.
Pestic Biochem Physiol ; 170: 104671, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980069

RESUMO

TEB belongs to the family of triazole fungicides and it is used to protect agricultural crop plants from fungal pathogens. The information regarding its cardiotoxic effects through different pathways particularly by perturbing the oxidative balance and causing damage to the myocardium is still limited. In the present study, oxidative and histopathologic damages caused by TEB in the cardiac tissue of male adult rats, were evaluated. Rats were exposed orally to TEB at 0.9, 9, 27 and 45 mg/kg b.w. for 28 days. Results showed that following TEB treatment malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP), antioxidant enzyme activities (GPx and GR) and GSSG levels increased, while GSH levels and thus the GSH/GSSG ratio decreased. Superoxide dismutase (SOD) and catalase (CAT) initially increased at the doses of 0.9, 9 and 27 mg/kg b.w. and then decreased at the dose of 45 mg/kg b.w. Moreover, western blot analysis showed that TEB increased SOD1, CAT and HSP70 protein levels after 24 h. Furthermore, TEB induced various histological changes in the myocardium, including leucocytic infiltration, hemorrhage congestion of cardiac blood vessels and cytoplasmic vacuolization. Therefore, our investigation revealed, that TEB exhibits cardiotoxic effects by changing oxidative balance and damaging the cardiac tissue.


Assuntos
Glutationa , Estresse Oxidativo , Animais , Antioxidantes , Catalase , Glutationa Peroxidase , Masculino , Malondialdeído , Ratos , Ratos Wistar , Superóxido Dismutase , Triazóis/toxicidade
15.
Ecotoxicol Environ Saf ; 205: 111367, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971454

RESUMO

Tebuconazole (TBZ), an azole pesticide, is one of the most frequently detected fungicides in surface water. Despite its harmful effects, mainly related to endocrine disturbance, the consequences of TBZ exposure in amphibians remain poorly understood. Here, we investigated the adverse and delayed effects of TBZ chronic exposure on a native anuran species, often inhabiting cultivated areas, the Italian tree frog (Hyla intermedia). To disclose the multiple mechanisms of action through which TBZ exerts its toxicity we exposed tadpoles over the whole larval period to two sublethal TBZ concentrations (5 and 50 µg/L), and we evaluated histological alterations in three target organs highly susceptible to xenobiotics: liver, kidney, and gonads. We also assessed morphometric and gravimetric parameters: snout-vent length (SVL), body mass (BM), liver somatic index (LSI), and gonad-mesonephros complex index (GMCI) and determined sex ratio, gonadal development, and differentiation. Our results show that TBZ induces irreversible effects on multiple target organs in H. intermedia, exerting its harmful effects through several pathological pathways, including a massive inflammatory response. Moreover, TBZ markedly affects sexual differentiation also by inducing the appearance of sexually undetermined individuals and a general delay of germ cell maturation. Given the paucity of data on the effects of TBZ in amphibians, our results will contribute to a better understanding of the environmental risk posed by this fungicide to the most endangered group of vertebrates.


Assuntos
Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Animais , Anuros/crescimento & desenvolvimento , Gônadas/efeitos dos fármacos , Larva/efeitos dos fármacos , Diferenciação Sexual/efeitos dos fármacos
16.
Environ Pollut ; 267: 115450, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32892009

RESUMO

Penconazole is a widely used chiral triazole bactericide that may adversely affect the environment. It contains two corresponding enantiomers and there may be differences in toxicity between the isomers. Therefore, in this study, we exposed zebrafish embryos to different concentrations of the penconazole enantiomer to study the developmental toxicity and neurotoxicity of penconazole on zebrafish and the difference in toxicity between enantiomers. The results showed that penconazole exposure caused adverse effects on zebrafish embryos, such as autonomous motor abnormalities, heart rate slowing, and increased deformity, resulting in significant developmental toxicity. Meanwhile, also caused the zebrafish larvae to slow movement, the neurotransmitter content and nervous system related gene expression significantly changed, which proved that penconazole also caused neurotoxicity to zebrafish. Interestingly, our results also clearly show that (+)-penconazole is significantly more toxic to zebrafish than (-)-penconazole at the same concentration, whether it is developmental toxicity or neurotoxicity, which suggests that we should focus on (+)-penconazole more when conducting toxicological studies on penconazole.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Embrião não Mamífero , Larva , Triazóis/toxicidade
17.
Ecotoxicol Environ Saf ; 204: 111040, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32798748

RESUMO

Tebuconazole (TEB) is a common triazole fungicide that is widely used throughout the world in agriculture applications. We previously reported that TEB induces cardiac toxicity in rats. The aim of this study was to investigate the underlying mechanism of the toxicity induced by TEB in cardiac cells. TEB induced dose-dependent cell death in H9c2 cardiomyoblasts and in adult rat ventricular myocytes (ARVM). The comet assay and western blot analysis showed a concentration-dependent increase in DNA damage and in p53 and p21 protein levels 24 h after TEB treatment. Our findings also showed that TEB triggered the mitochondrial pathway of apoptosis as evidenced by a loss of mitochondrial transmembrane potential (ΔΨm), an increase in Bax/Bcl-2 ratio, an activation of caspase-9 and caspase-3, a cleavage of poly (ADP-ribose) polymerase (PARP) and an increase in the proportion of cells in the sub-G1 phase. In addition, TEB promoted ROS production in cardiac cells and consequently increased the amounts of MDA, the end product of lipid peroxidation. Treatment of cardiomyocytes with the ROS scavenger N-acetylcysteine reduced TEB-induced DNA damage and activation of the mitochondrial pathway of apoptosis. These results indicate that the genotoxic and cytotoxic effects of TEB are mediated through a ROS-dependent pathway in cardiac cells.


Assuntos
Apoptose , Cardiotoxicidade/metabolismo , Dano ao DNA , Fungicidas Industriais/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Triazóis/toxicidade , Animais , Cardiotoxicidade/etiologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Ratos , Ratos Wistar
18.
Aquat Toxicol ; 226: 105584, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32795838

RESUMO

There is increasing evidence about negative effects of fungicides on non-target organisms, including parasitic species, which are key elements in food webs. Previous experiments showed that environmentally relevant concentrations of fungicide tebuconazole are toxic to the microparasite Metschnikowia bicuspidata, a yeast species that infects the planktonic crustacean Daphnia spp. However, due to their short-term nature, this and other experimental studies were not able to test if parasites could potentially adapt to these contaminants. Here, we tested if M. bicuspidata parasite can adapt to tebuconazole selective pressure. Infected D. magna lineages were reared under control conditions (no tebuconazole) and environmentally realistic tebuconazole concentrations, for four generations, and their performance was compared in a follow-up reciprocal assay. Additionally, we assessed whether the observed effects were transient (phenotypic) or permanent (genetic), by reassessing parasite fitness after the removal of selective pressure. Parasite fitness was negatively affected throughout the multigenerational exposure to the fungicide: prevalence of infection and spore load decreased, whereas host longevity increased, in comparison to control (naive) parasite lineages. In a follow-up reciprocal assay, tebuconazole-conditioned (TEB) lineages performed worse than naive parasite lineages, both in treatments without and with tebuconazole, confirming the cumulative negative effect of tebuconazole. The underperformance of TEB lineages was rapidly reversed after removing the influence of the selective pressure (tebuconazole), demonstrating that the costs of prolonged exposure to tebuconazole were phenotypic and transient. The microparasitic yeast M. bicuspidata did not reveal potential for rapid evolution to an anthropogenic selective pressure; instead, the long-term exposure to tebuconazole was hazardous to this non-target species. These findings highlight the potential environmental risks of azole fungicides on non-target parasitic fungi. The underperformance of these microbes and their inability to adapt to such stressors can interfere with the key processes where they intervene. Further research is needed to rank fungicides based on the hazard to non-target fungi (parasites, but also symbionts and decomposers), towards more effective management and protective legislation.


Assuntos
Daphnia/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Metschnikowia/efeitos dos fármacos , Modelos Biológicos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Adaptação Fisiológica/efeitos dos fármacos , Animais , Daphnia/microbiologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Metschnikowia/crescimento & desenvolvimento
19.
Chem Biol Interact ; 330: 109114, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735800

RESUMO

Tebuconazole (TEB) is a broad-spectrum conazole fungicide that has been used in agriculture in the control of foliar and soil-borne diseases of many crops. The present study has investigated the adverse effects of subchronic exposure to TEB on the kidney of male rats. Animals were divided into four equal groups and treated with TEB at increasing doses 0.9, 9 and 27 mg/kg body weight for 28 consecutive days. The results showed that TEB induced oxidative stress in the kidney demonstrated by an increase in malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP) levels and DNA damage, as compared to the controls. Furthermore, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities were increased in the renal tissue of treated rats. Moreover, significant decrease in reduced glutathione (GSH) content in TEB-treated rats was observed, while oxidized glutathione (GSSG) levels were increased, thus a marked fall in GSH/GSSG ratio was registered in the kidney. Glutathione reductase (GR) activity showed a significant increase after TEB exposure. Moreover, TEB down-regulated the expression of Bcl2 and up-regulated the expression of Bax and caspase 3, which triggered apoptosis via the Bax/Bcl2 and caspase pathway. Also, TEB administration resulted in altered biochemical indicators of renal function and varying lesions in the overall histo-architecture of renal tissues. Taken together, our findings brought into light the renal toxicity induced by TEB, which was found to be significant at low doses.


Assuntos
Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Triazóis/toxicidade , Animais , Relação Dose-Resposta a Droga , Fungicidas Industriais/toxicidade , Regulação da Expressão Gênica , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Glutationa Redutase/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Oxirredução , Ratos , Ratos Wistar
20.
Bull Environ Contam Toxicol ; 105(4): 620-625, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32857223

RESUMO

Due to their ecological importance, fungi are suitable indicator organisms for anthropogenic stress. To estimate fungal biomass, the fungal membrane molecule ergosterol is often quantified as a proxy. Estimates based on ergosterol may, however, be distorted by exposure to demethylase inhibiting (DMI) fungicides, interfering with sterol synthesis. To test this hypothesis, we exposed ten fungal species to the DMI fungicide tebuconazole and measured concentrations of ergosterol and DNA per unit dry mass of the fungal hyphae. The latter served as alternative biomass proxy that is not specifically targeted by tebuconazole. Effects of tebuconazole on ergosterol concentrations were species-specific, while concentrations were on average reduced by 13%. In contrast, DNA concentrations were on average increased by 13%. We demonstrate that DMI fungicides - at close to field relevant levels - can distort fungal biomass estimation, complicating the use of this endpoint for environmental management.


Assuntos
Fungos/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Biomarcadores , Biomassa , Ergosterol
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