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1.
Exp Parasitol ; 221: 108059, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338468

RESUMO

Treatment for visceral leishmaniasis (VL) is hindered mainly by the toxicity and/or high cost of therapeutic drugs. In addition, parasite resistance has been registered. Thus, there is an urgent need for the identification of novel, effective and low-cost antileishmanial agents. Since drug discovery is a long and expensive process, drug repositioning for treatment of leishmaniasis should be considered. In the present study, Ivermectin (IVE), a broad-spectrum drug used for treatment of parasitic diseases, was evaluated in vitro and in vivo against Leishmania infantum species. Results in vitro showed that IVE presented 50% Leishmania and macrophage inhibitory concentrations (IC50 and CC50, respectively) of 3.64 ± 0.48 µM and 427.50 ± 17.60 µM, respectively, with a selectivity index (SI) of 117.45; whereas Amphotericin B (AmpB), which was used as control, showed IC50 and CC50 values of 0.12 ± 0.05 µM and 1.06 ± 0.23 µM, respectively, with a corresponding SI of 8.90. Treatment with IVE effectively reduced the infection percentage and parasite burden in infected and treated macrophages and displayed a prophylactic activity by inhibiting macrophage infection with pre-treated parasites. Furthermore, preliminary studies suggested that IVE targets the parasite's mitochondria. Activity of IVE in its free format or incorporated into Pluronic® F127-based polymeric micelles (IVE/Mic) was also evaluated in vivo as a treating drug for L. infantum-infected BALB/c mice. Miltefosine was used as a control. Results showed that Miltefosine, IVE and IVE/Mic-treated animals presented significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as well as development of an antileishmanial Th1-type immune response one and 15 days after treatment. Notably, IVE/Mic showed a better parasitological and immunological response in comparison to other alternative treatments. In conclusion, results suggest that IVE/Mic could be considered in future studies as a therapeutic alternative to treat VL.


Assuntos
Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Anfotericina B/farmacologia , Animais , Antiprotozoários/toxicidade , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Concentração Inibidora 50 , Ivermectina/toxicidade , Macrófagos Peritoneais/efeitos dos fármacos , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Baço/parasitologia
2.
Bull Environ Contam Toxicol ; 105(4): 582-587, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32948914

RESUMO

Oreochromis niloticus was exposed to 10.0 ppb of organophosphate insecticide chlorpyrifos (CPF) and avermectin insecticides abamectin (ABM) and emamectin benzoate (EB) for 48 and 96 h. RBC and Hb decreased in CPF- and ABM-exposed fish after 96-h. Plasma ALT, AST, cortisol, and glucose increased in 96-h CPF-, ABM- and EB-exposed fish, while plasma ions declined in 96-h CPF-exposed ones. Insecticides caused alterations in liver oxidative stress parameters. In fish exposed to CPF, CAT increased after 48-h whereas it decreased after 96-h. Also, CAT declined in 48- and 96-h ABM-exposed fish, whereas it elevated in 48-h EB-exposed ones. Insecticides caused decreases in SOD at 48- and 96-h and in GR after 96-h. GSH elevated in CPF-exposed fish after 48-h, while it decreased in all the tested insecticide exposures after 96-h. Malondialdehyde of fish exposed to insecticides for 96-h increased. Consequently, toxic effects of insecticides on O. niloticus were generally as CPF > ABM > EB.


Assuntos
Clorpirifos/toxicidade , Ciclídeos , Inseticidas/toxicidade , Ivermectina/análogos & derivados , Poluentes Químicos da Água/toxicidade , Animais , Análise Química do Sangue/veterinária , Testes Hematológicos/veterinária , Ivermectina/toxicidade , Fígado/efeitos dos fármacos , Fígado/enzimologia , Oxirredução , Distribuição Aleatória , Testes de Toxicidade Aguda/veterinária
3.
Mar Pollut Bull ; 157: 111375, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32658716

RESUMO

At the end of March 2020, ivermectin was confirmed as a drug for COVID-19 treatment. A significant amount of ivermectin could deposit into sediments of the semi-closed Mediterranean Sea, where three European COVID-19 epicenters are located: Italy, Spain, and France. Meiobenthic nematodes were exposed to three ivermectin doses (1.8 ng.g-1, 9 ng.g-1, and 18 ng.g-1) for 10 days. Ivermectin caused a great reduction in abundance. However, the diversity indices decreased only at high doses. Ivermectin disadvantaged the 1B-Cr-Id functional type (non-selective deposit feeders and nematodes with circular or indistinct amphids) and benefited the 2A-REL-Sp type (epistrate feeders and nematodes with rounded or elongated loop amphids). Thus, Trophic Diversity and Amphideal Diversity index values increased with sedimentary ivermectin enrichment. Large amphideal foveas were more efficient for 2A-REL-Sp nematodes to avoid ivermectin. The responses of the functional type 2A-REL-Sp and corresponding taxa predict post-COVID-19 environmental concerns and the bioaccumulation of ivermectin in seafoods.


Assuntos
Antivirais/toxicidade , Infecções por Coronavirus , Ivermectina , Nematoides , Pandemias , Pneumonia Viral , Animais , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , França , Humanos , Itália , Ivermectina/toxicidade , Mar Mediterrâneo , Espanha
4.
Aquat Toxicol ; 225: 105528, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32569996

RESUMO

Abamectin (ABM) has been extensively used in Chinese aquaculture systems for parasite control, but no information is available regarding its effects on the important freshwater commercial fish species Schizothorax prenanti. We performed an acute toxicity test to determine the effects of ABM on S. prenanti, and the 48- and 96-h median lethal concentration values were 33.32 and 15.98 µg/L, respectively. In a second test, animals were exposed to sublethal concentrations of ABM (0.5, 2 or 8 µg/L) for 8 days, and various cytological and biochemical parameters were measured. ABM caused DNA damage in hepatocytes, with significant increases in Olive Tail Moment values and 8-hydroxy-2'-deoxyguanosine levels. Hepatocytic apoptosis occurred following all treatments, and was accompanied by an increase in reactive oxygen species (ROS) generation and caspase activity in a dose- and time-dependent manner. In addition, there were significant decreases in glutathione peroxidase levels and superoxide dismutase and catalase activity and increases in malonaldehyde levels. ABM-induced hepatocytic apoptosis in S. prenanti was probably triggered by ROS generation following a cascade reaction of caspases in mitochondrial or death receptor pathways, which caused antioxidant inhibition, oxidative product accumulation, and DNA damage in the liver.


Assuntos
Cyprinidae/metabolismo , Dano ao DNA , Ivermectina/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Cyprinidae/genética , Cyprinidae/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Água Doce/química , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Ivermectina/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Oxirredução , Superóxido Dismutase/metabolismo
5.
Chemosphere ; 259: 127448, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32593828

RESUMO

Ivermectin (IVM), a broad-spectrum antiparasitic drug, is widely used in agriculture and animal husbandry. Due to widespread use and little metabolism in animals, the toxicity of IVM has received increasing attention. The accumulation of IVM in animal tissues and the excretion of urine and feces in the environment is the major source of potential toxicity. Human consumption of meat or milk contaminated with livestock can result in exposure to high levels of IVM exposure. The aim of this study was to reveal the cytotoxic mechanism of IVM in model cell HeLa in vitro, in order to provide a theoretical basis for the safe and rational use of IVM. Here we observed the γH2AX and 8-oxodG foci to detect the DNA damage in HeLa cells. As expected, we found that IVM can induce oxidative double-stranded damage in HeLa cells, indicating that IVM has potential genotoxicity to human health. In addition, we observed the formation of LC3-B in HeLa cells, the accumulation of Beclin1, the degradation of p62 and the activation of the AMPK/mTOR signal transduction pathway. This suggests that IVM confers cytotoxicity through autophagy mediated by the AMPK/mTOR signaling pathway. We conclude that IVM produces genotoxicity and cytotoxicity by inducing DNA damage and AMPK/mTOR-mediated autophagy, thereby posing a potential risk to human health.


Assuntos
Inseticidas/toxicidade , Ivermectina/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antiparasitários/farmacologia , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Dano ao DNA/efeitos dos fármacos , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
6.
Aquat Toxicol ; 224: 105519, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32502848

RESUMO

Emamectin benzoate (EB) is a prophylactic pharmaceutical used to protect Atlantic salmon (Salmo salar) smolts migrating out of rivers and into the ocean against sea lice parasites. Randomized control trials comparing the marine survival of smolts treated with EB to a control group is used to calculate the fraction of marine mortality attributable to sea lice parasitism. However, it is assumed that there is no baseline difference in survival induced by the application of EB treatment. We used a combined laboratory and field study approach to investigate the potential impacts of EB treatment on behaviour and survival of hatchery-reared Atlantic salmon in western Norway. In aquaria experiments, EB-treated salmon smolts did not differ significantly in exploratory behaviour. Fish from treated groups responded similarly to simulated predator attack with spontaneous escape and elevated gill beat rate. Three rivers in the Osterfjord system of western Norway were selected for field experiments, Dale, Vosso, and Modalen. Dale River smolts were treated with intraperitoneal EB injections and had lower probability of detection in a wolf trap downstream of the release site than control smolts. Salmon smolts raised in the Vosso River hatchery were treated with EB delivered in their food and were detected on PIT antennas at the rivermouth of Vosso and Modalen at lower rates than control fish, but only when released at downstream sites. Calculation of risk ratios suggested that the bias in mortality caused by treatment with EB decreased the estimated survival of treated fish from an expected 18%to 46%, reducing the observable negative impact of sea lice on Atlantic salmon smolts in randomized control trials. The results suggest that estimates of the fraction of mortality attributable to sea lice may be underestimated due to lower baseline survival of treated fish caused by treatment and bring urgent attention towards a potential systematic underestimation of the impacts of sea lice on wild salmon.


Assuntos
Copépodes/efeitos dos fármacos , Ivermectina/análogos & derivados , Salmo salar/crescimento & desenvolvimento , Poluentes Químicos da Água/toxicidade , Migração Animal/efeitos dos fármacos , Animais , Brânquias/efeitos dos fármacos , Ivermectina/farmacologia , Ivermectina/toxicidade , Modelos Teóricos , Noruega , Distribuição Aleatória , Rios/química , Salmo salar/metabolismo , Análise de Sobrevida , Poluentes Químicos da Água/farmacologia
7.
Ecotoxicology ; 29(9): 1486-1499, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32388636

RESUMO

This study evaluated the toxicity of pesticide formulations Kraft® 36 EC (active ingredient-a.i. abamectin) and Score® 250 EC (a.i. difenoconazole), and their mixtures in Daphnia magna at different biological levels of organization. Survival, reproduction and biochemical markers (cholinesterase (ChE), catalase (CAT) and lipid peroxidation (LPO)) were some of the endpoints evaluated. Total proteins and lipids were also studied together with energy consumption (Ec). D. magna neonates were exposed for 96 h to Kraft (2, 4, and 6 ng a.i./L) and Score (12.5, 25, and 50 µg a.i./L) for the biochemical experiments, and for 15 days to abamectin (1-5 ng a.i./L) and to difenoconazole (3.12-50 µg a.i./L) to assess possible changes in reproduction. Exposures of organisms to both single compounds did not cause effects to antioxidant and detoxifying enzymes, except for LPO occurring at the highest concentration of difenoconazole tested. For ChE and CAT there was enzymatic induction in mixture treatments organisms, occurring at minor pesticides concentrations for CAT and at the two highest concentrations for ChE. There were no significant differences for total protein in D. magna but lipids showed an increase at the highest concentrations of pesticide mixture combinations. There was a significant increase of Ec in individuals of all treatments tested. In the chronic test, increased fecundity occurred for D. magna under difenoconazole exposures and mixtures. This study demonstrated that mixtures of these pesticides caused greater toxicity to D. magna than when tested individually, except for Ec. Therefore, effects of mixtures are very hard to predict only based on information from single compounds, which most possibly is the result of biological complexity and redundancy in response pathways, which need further experimentation to become better known.


Assuntos
Daphnia/fisiologia , Dioxolanos/toxicidade , Ivermectina/análogos & derivados , Praguicidas/toxicidade , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Colinesterases , Ivermectina/toxicidade , Reprodução , Testes de Toxicidade Aguda
8.
Chemosphere ; 253: 126658, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32259680

RESUMO

The objective of the present study was to determine the susceptibility of entomopathogenic nematodes to ivermectin and thiabendazole. Soil samples collected from the municipalities of Irapuato and León, Guanajuato, Mexico, were obtained, from which the entomopathogenic nematodes (EPNs) of the Steinernematidae and Heterorhabditidae families were isolated. The samples were classified from livestock and nonlivestock soils, and the susceptibility of EPNs to anthelmintics was determined with the larval motility assay (LMA, 24 h) and the larval migration inhibition assay (LMI assay, 48 h). Sterile distilled water (T1) and treatments with 1% ivermectin diluted in 5% DMSO (dimethyl sulfoxide) (T2) and 5% thiabendazole diluted in 5% DMSO (T3) were applied to infective juvenile larvae. Analysis of variance was performed with a factorial design and Tukey's test at 0.05 probability. In addition, different concentrations of ivermectin (0.1, 0.5, 1, 1.2, 1.5, and 2 µg) and thiabendazole (1, 5, 10, 12, 15, and 20 mg) were evaluated to perform a Probit analysis to determine their LC50. All strains of EPNs were susceptible to ivermectin in both the LMA and LMI assay. The results show that EPNs are susceptible to ivermectin and thiabendazole, and the degree depends on the type of test performed, the chemical product used, and the origin of the strain of EPN.


Assuntos
Anti-Helmínticos/toxicidade , Ivermectina/toxicidade , Rabditídios/fisiologia , Tiabendazol/toxicidade , Animais , Larva/efeitos dos fármacos , México , Solo
9.
Ecotoxicol Environ Saf ; 194: 110452, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171961

RESUMO

The commercial farming of Atlantic salmon, Salmo salar, may require the periodic application of emamectin benzoate (EB) treatments to reduce the effects of biological pests, such as sea lice. As a result, EB is detected in sediments beneath these fish farms at considerable levels. Literature sediment toxicity data for EB for marine benthic species is only available for 10-day sediment toxicity tests, which might be too short to assess field effects. Here, we present a sediment toxicity test to determine 28-day mortality and growth effect concentrations for the non-target polychaete worm Arenicola marina, the crustacean Corophium volutator and the mollusk Cerastoderma edule using a marine microcosm setup. Results indicate that no concentration-dependent increase of mortality and growth rate was apparent to A. marina and C. edule. But for C. volutator, a concentration-dependent increase in mortality was observed, resulting in a calculated 28-d LC50 of 316 µg/kg dry sediment (95% confidence interval: 267-373 µg/kg dry sediment). There were significant effects on C. volutator growth rate at concentrations of 100 µg/kg dry sediment and above (NOEC = 30 µg/kg dry sediment). These observations show that C. volutator is more sensitive to EB than A. marina, which differs from results reported in previous studies. Comparison to the most sensitive NOEC (30 µg/kg dry sediment) found for C. volutator (organisms of 8-11 mm length), shows that the Environmental Quality Standard, derived by the Scottish Environment Protection Agency in 2017 which based on freshwater species data (NOEC = 1.175 µg/kg dry sediment), are relatively strict and is sufficiently protective for the marine species tested in this paper.


Assuntos
Ivermectina/análogos & derivados , Poluentes Químicos da Água/toxicidade , Anfípodes/efeitos dos fármacos , Animais , Monitoramento Ambiental/métodos , Água Doce , Sedimentos Geológicos , Ivermectina/toxicidade , Poliquetos , Testes de Toxicidade Crônica
10.
Chemosphere ; 250: 126271, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32114345

RESUMO

Pesticides and veterinary products that are globally used in farming against pests and parasites are known to impact non-target beneficial organisms. While most studies have tested the lethal and sub-lethal effects of single chemicals, species are exposed to multiple contaminants that might interact and exacerbate the toxic responses of life-history fitness components. Here we experimentally tested an ecotoxicological scenario that is likely to be widespread in nature, with non-target dung communities being exposed both to cattle parasiticides during the larval stage and to agricultural insecticides during their adult life. We assessed the independent and combined consumptive effects of varying ivermectin and spinosad concentration on juvenile life-history and adult reproductive traits of the widespread yellow dung fly (Scathophaga stercoraria; Diptera: Scathophagidae). Larval exposure to ivermectin prolonged development time and reduced egg-to-adult survival, body size, and the magnitude of the male-biased sexual size dimorphism. The consumption by the predatory adult flies of spinosad-contaminated prey showed an additional, independent (from ivermectin) negative effect on female clutch size, and subsequent egg hatching success, but not on the body size and sexual size dimorphism of their surviving offspring. However, there were interactive synergistic effects of both contaminants on offspring emergence and body size. Our results document adverse effects of the combination of different chemicals on fitness components of a dung insect, highlighting transgenerational effects of adult exposure to contaminants for their offspring. These findings suggest that ecotoxicological tests should consider the combination of different contaminants for more accurate eco-assessments.


Assuntos
Ecotoxicologia/métodos , Insetos/efeitos dos fármacos , Praguicidas/farmacologia , Animais , Antiparasitários/farmacologia , Tamanho Corporal/efeitos dos fármacos , Bovinos , Dípteros/efeitos dos fármacos , Combinação de Medicamentos , Interações Medicamentosas , Feminino , Ivermectina/toxicidade , Larva/efeitos dos fármacos , Macrolídeos/toxicidade , Masculino , Praguicidas/análise , Reprodução/efeitos dos fármacos
11.
Environ Toxicol Chem ; 39(4): 863-872, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32181912

RESUMO

It is often difficult to compare studies examining the effects of endectocides on dung fauna because of different experimental approaches, for example, active ingredients (eprinomectin, doramectin, ivermectin, moxidectin) and formulations (injectable, pour-on, spiked). To gain a better understanding, we performed a quantitative meta-analysis using 22 studies to assess the overall effect of endectocide residues on the occurrence (presence or absence) and abundance of aphodiine dung beetles. Our results document a positive effect on the occurrence of adult beetles, indicating that adults tend to be attracted to dung with residues. Conversely, larvae are less likely to occur in the presence of residues. Thus, either adults that colonize dung with residues do not lay eggs or, more likely, the larvae that hatch from these eggs die early in development. Abundance of adult and larval stages was shown to be significantly reduced in dung containing residues. When individual endectocides were compared, only ivermectin demonstrated a significantly negative effect on the abundance of both adults and larvae, possibly owing to a small sample size for other agents. In laboratory studies, only dung "spiked" with endectocides reduced the abundance of larvae, whereas during field research, only pour-on applications were shown to reduce the abundance of larvae. The present study further documents the nontarget effects of endectocide residues on dung-dwelling organisms, provides robust evidence on the consequences of different application methods, and emphasizes the need for standardized methodological techniques in future studies. Environ Toxicol Chem 2020;39:863-872. © 2020 SETAC.


Assuntos
Besouros/efeitos dos fármacos , Resíduos de Drogas/toxicidade , Poluentes Ambientais/toxicidade , Ivermectina/análogos & derivados , Drogas Veterinárias/toxicidade , Animais , Besouros/crescimento & desenvolvimento , Resíduos de Drogas/análise , Poluentes Ambientais/análise , Fezes/química , Ivermectina/análise , Ivermectina/toxicidade , Larva/efeitos dos fármacos , Gado , Drogas Veterinárias/análise
12.
Chemosphere ; 250: 126321, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32135440

RESUMO

The lacewing, Chrysoperla sinica, is an important predatory insect, which plays an important role in the integrated pest management of agroforestry pests. However, the extensive use of insecticides negatively affects C. sinica. The acute toxicity, risk level, and, sublethal effects on growth and production, predation ability, protective enzyme activity and genotoxicity of four insecticides: indoxacarb, emamectin benzoate, imidacloprid and lambda-cyhalothrin to C. sinica were studied. The results showed that all four insecticides had lethal toxicity to larvae of C. sinica. Among them, emamectin benzoate had the highest toxicity with LC50 value of 7.41 mg/L. The insecticides also had different effects on the growth and reproduction of C. sinica, of which lambda-cyhalothrin had the greatest impacts. Even at a very low LC1 concentration (3.37 mg/L), it had strong impacts on the growth, reproduction and predatory ability of C. sinica. The four insecticides also caused a decrease in the predatory ability of the lacewing, of which lambda-cyhalothrin had the greatest effect. During the larval stage, the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were significantly decreased by the four insecticides. At the pupal and adult stages, the effects of the four insecticides on the activities of protective enzymes were different, and the activities of SOD, CAT and POD decreased or increased. Indoxacarb and lambda-cyhalothrin exposure induced DNA damage in the haemocytes of C. sinica and produced obvious genotoxicity. These results provide important scientific basis for the rational use of these insecticides and the protection and utilization of lacewing.


Assuntos
Insetos/efeitos dos fármacos , Inseticidas/toxicidade , Animais , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Larva/efeitos dos fármacos , Neonicotinoides/toxicidade , Nitrilos , Nitrocompostos/toxicidade , Oxazinas/toxicidade , Comportamento Predatório/efeitos dos fármacos , Pupa/efeitos dos fármacos , Piretrinas , Testes de Toxicidade Aguda
13.
Ecotoxicol Environ Saf ; 194: 110446, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171122

RESUMO

Pesticides can affect all receiving compartments, especially soils, and their fate and effects may be enhanced by temperature, increasing their risk to ecological functions of soils. In Brazil, the most widely used pesticides are the insecticide Kraft 36 EC® (a.s. abamectin) and the fungicide Score 250 EC® (a.s. difenoconazole), which are commonly used in strawberry, often simultaneously as a mixture. The aim of this study was to evaluate the toxicity of realistic environmental applications, single and in mixtures, for both pesticides to the springtail Folsomia candida and the plant species Allium cepa (onion) and Lycopersicum esculentum (tomato). Mesocosms filled with Brazilian natural soil (lattosolo) were dosed with water (control), Kraft (10.8 g a.s/ha), Score (20 g.a.s/ha) and Kraft + Score (10.8 + 20 g a.s./ha). The applications were repeated every 7 days, during 18 days of experiment, and simulating rainfall twice a week. Collembola reproduction tests were conducted with soils from the first (day 1) and last day (day 18) of experiment for each treatment. Plant toxicity tests were carried out in the experimental units. The experiments were run at 23 °C and 33 °C. Kraft, alone and in the binary mixture, showed high toxicity to the springtails in soils from both days 1 and 18, especially at 23 °C where it caused 100% mortality. Score however, was not toxic to the springtails. Plant growth was reduced by Score, but responses varied depending on temperature. This study indicates a high environmental risk of the insecticide Kraft, particularly at lower temperatures (23 °C), and an influence of temperature on pesticide fate and effects.


Assuntos
Dioxolanos/toxicidade , Ivermectina/análogos & derivados , Poluentes do Solo/toxicidade , Triazóis/toxicidade , Animais , Artrópodes/fisiologia , Brasil , Exposição Ambiental , Fungicidas Industriais , Inseticidas/toxicidade , Ivermectina/toxicidade , Praguicidas/toxicidade , Solo , Temperatura , Testes de Toxicidade
14.
PLoS One ; 15(2): e0228817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32032382

RESUMO

Abamectin is a common biocide used to control agricultural insect pests. However, the water insolubility of abamectin may result in extra organic solvent introduced in the environment. To solve this issue, it is desirable to develop nanoformulations to encapsulate abamectin with environment-friendly polymers. In this study, two polylactic acid based abamectin nanoformulations were prepared. The average particle sizes, measured by dynamic light scattering and transmission electron microscope, were 240 nm and 150 nm, respectively. The insecticidal activity of these nano-formulated abamectin was examined in the laboratory on the pea aphid, Acyrthosiphon pisum (Hemiptera: Aphididae). The acute toxicity of nano-formulated abamectin on non-target aphid predator Adalia bipunctata (Coleoptera: Coccinellidae) was also evaluated by topical, residual and oral exposure. The two nano-formulated abamectin had comparable insecticidal effect with commercial abamectin formulation against the pea aphid. Taking median lethal concentration (LC50) as the toxicological endpoint, nanoformulations had higher contact toxicity and lower oral toxicity to first-instar larvae of the predator A. bipunctata. These results are expected to contribute to the application of solvent-free nano-formulated pesticides that comply with the integrated pest management (IPM) strategies.


Assuntos
Afídeos/efeitos dos fármacos , Besouros/efeitos dos fármacos , Inseticidas/toxicidade , Ivermectina/análogos & derivados , Nanoestruturas/química , Poliésteres/química , Animais , Afídeos/crescimento & desenvolvimento , Besouros/crescimento & desenvolvimento , Composição de Medicamentos , Inseticidas/química , Ivermectina/química , Ivermectina/toxicidade , Dose Letal Mediana , Tamanho da Partícula
15.
Artigo em Inglês | MEDLINE | ID: mdl-31899308

RESUMO

Glutathione S-transferases (GSTs) are a multifunctional protein superfamily that can catalyze the detoxification processes in an organism. In the present study, we determined the structure and function of GSTs in Chinese mitten crab (Eriocheir sinensis) by gene cloning, expression, and enzyme activity in order to investigate the metabolic detoxification of GSTs in the hepatopancreas and muscles under three pesticide (trichlorfon, ß-cypermethrin and avermectin) stresses. Multiple sequence alignment analysis showed that all the three Es-GST genes possessed N-terminal, and C-terminal domain as well as G-binding sites, while Es-GST2 and Es-GST3 contained Mu-type GST-specific Mu-loop structures. Phylogenetic tree analysis revealed that the three Es-GSTs belonged to the Mu-type GST of crustaceans. The quantitative real-time PCR revealed that the three Es-GSTS were expressed in 9 tissues of Eriocheir sinensis, with highest expression in hepatopancreas and muscle. The expression of the three Es-GSTS significantly increased in the hepatopancreas and muscle under the three pesticide stresses compared to the control group, and a steady increase in GST activity was observed. The study showed that the three Es-GSTs belong to the Mu-type GST of the crustaceans and might play an important role in the metabolic detoxification in Eriocheir sinensis.


Assuntos
Braquiúros/enzimologia , Glutationa Transferase , Hepatopâncreas/metabolismo , Inseticidas , Músculos/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Expressão Gênica , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Inativação Metabólica , Inseticidas/metabolismo , Inseticidas/toxicidade , Ivermectina/análogos & derivados , Ivermectina/metabolismo , Ivermectina/toxicidade , Piretrinas/metabolismo , Piretrinas/toxicidade , Triclorfon/metabolismo , Triclorfon/toxicidade
16.
Biomed Pharmacother ; 124: 109841, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31972360

RESUMO

Avermectins are broad-spectrum antiparasitic drugs in veterinary and human medication. The current study aimed to examine the toxic effects of ivermectin (IVM) and doramectin (DRM), with or without co-treatment of vitamin E (Vit.E) and selenium (Se) on apoptosis, oxidative stress and male fertility in Wistar rats. Twenty five adult male animals were divided into five groups; G1; was control (CTL) received saline, G2; IVM (0.2 mg/kg b.w), G3; IVM plus Vit.E/Se (80/1.6 mg/kg b.w, respectively), G4; DRM (0.2 mg/kg b.w), and G5; DRM plus Vit.E/Se. Both IVM and DRM were given by subcutaneous (s.c) injections while Vit.E/Se was orally given. All treatments were administered once weekly for four consecutive weeks. By 24 h after the last treatment, the animals were sacrificed. Blood and tissue samples were collected for hematology, serobiochemistry, histopathology, and molecular assays for hepatic/ renal toxicities, oxidative stress, cell viability and fertility parameters. Apoptosis of the hepatic cells obtained from the treated rats was assayed by detection of annexin-V using the flow cytometric assay (FCA). The proliferating cellular nuclear antigen (PCNA) and DNA fragmentation in the treated rats' testicular tissues were also assayed. Moreover, the direct effects of IVM or DRM with or without concomitant administration of Vit.E/Se on testicular cells isolated from adult rat were also performed in vitro. Apoptosis of those cultured testicular cells in response to the different treatments was assayed by detection of the inhibition-concentration fifty (IC50) using the SRB method, and evaluating the viable versus apoptotic cells microscopically after staining with acridine orange-ethidium bromide (AO/EB). In conclusion, both avermectins induced apoptosis in the living and cultured cells, while those antioxidants; Vit.E and Se, reduced the oxidative stress and cytotoxicity both in vivo and in vitro, either. Furthermore, the reprotoxicity and reduced male fertility were seriously evoked by IVM, but not DRM with dramatic ameliorative effect of Vit.E/Se if concomitantly administered. Avermectins, especially ivermectin, should be given according to the dose recommended by the manufacturer company and repeated dosages should be given with Vit.E/Se.


Assuntos
Antiparasitários/toxicidade , Ivermectina/farmacologia , Testículo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Sinergismo Farmacológico , Fertilidade/efeitos dos fármacos , Ivermectina/administração & dosagem , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Selênio/toxicidade , Testículo/patologia , Vitamina E/administração & dosagem
17.
Chemosphere ; 242: 125240, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896183

RESUMO

The veterinary pharmaceutical ivermectin is commonly used against parasites of livestock. Excreted in dung it can have lethal and sublethal effects on non-target organisms developing in and living around cattle dung. Research in this realm typically investigates the impact of pharmaceuticals on dung-feeding insects by looking at juvenile development and survival, while fitness effects of adult exposure are largely neglected. We conducted laboratory experiments to assess combined effects of ivermectin on life history and reproductive traits of juvenile and adult yellow dung flies (Scathophaga stercoraria). Two treatments (12 and 24 µg ivermectin/kg wet dung) were used for the larvae reared in dung, and one much higher concentration (3000 µg ivermectin/kg sugar) for the adult flies (in addition to uncontaminated controls). Juvenile ivermectin exposure lead to smaller body size of male and female flies. Adult feeding on ivermectin-contaminated dung additionally resulted in adult male flies with smaller testes (and likely fewer sperm) that experienced reduced mating durations, resulting in lower probability of producing offspring. Exposure of adult flies to ivermectin lowered offspring production and survival for both sexes. Thus, treatment of livestock with pharmaceuticals such as ivermectin appears to have even more far-reaching sublethal ecological consequences than previously assumed by affecting not only flies at their larval stage but also adult mating behaviour and reproduction.


Assuntos
Antiparasitários/toxicidade , Insetos/efeitos dos fármacos , Ivermectina/toxicidade , Animais , Tamanho Corporal/efeitos dos fármacos , Bovinos , Ecologia , Fezes , Feminino , Insetos/fisiologia , Larva/efeitos dos fármacos , Gado , Masculino , Fenótipo , Reprodução/efeitos dos fármacos , Drogas Veterinárias/farmacologia
18.
Lancet Glob Health ; 8(1): e92-e100, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31839144

RESUMO

BACKGROUND: About 3·7 billion doses of ivermectin have been distributed in mass drug administration (MDA) campaigns globally over the past 30 years. At 10-100 times higher than current human doses, ivermectin is a known teratogen in mammals. During these campaigns with recommended doses, pregnant women might be inadvertently exposed. We therefore aimed to evaluate the existing evidence for serious and non-serious adverse events after ivermectin exposure in pregnant women. METHODS: For this systematic review and meta-analysis, we searched relevant databases and trial registry platforms on July 15, 2018, for randomised controlled trials (RCTs) and observational studies that reported adverse events in pregnant women. We did not use language or date restrictions. Outcomes of interest were spontaneous abortions, stillbirths, congenital anomalies, and neonatal death (serious adverse events), as well as maternal morbidity, preterm births, and low birthweight (adverse events). The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias Tool for RCTs. We did the meta-analysis of observational studies and RCTs separately. The quality of evidence was assessed using the GRADE approach. The study protocol is registered with PROSPERO, protocol CRD42016046914. FINDINGS: We identified 147 records, of which only five observational studies and one RCT were included for quantitative analysis; these studies were published between 1990 and 2008, and were done in six African countries. 893 women with 899 pregancy outcomes were included, of whom 496 pregnant women (500 pregnancy outcomes) received ivermectin inadvertently during MDA campaigns in the observational studies and 397 pregnant women (399 pregnancy outcomes) purposely received ivermectin as part of the open-label RCT. No study reported neonatal deaths, maternal morbidity, preterm births, or low birthweight. It is unclear whether exposure to ivermectin during pregnancy increases the risk of spontaneous abortions and stillbirths (odds ratio [OR] 1·15 [95% CI 0·75-1·78] with very low certainty of evidence for the four observational studies and 0·62 [0·18-2·14] with very low certainty of evidence for the RCT) or congenital anomalies (OR 1·69 [95% CI 0·83-3·41] with very low certainty of evidence for the five observational studies and 1·10 [0·07-17·65] with very low certainty of evidence for the RCT). INTERPRETATION: There is insufficient evidence to conclude on the safety profile of ivermectin during pregnancy. Treatment campaigns should focus additional efforts on preventing inadvertent treatment of pregnant women. FUNDING: Unitaid.


Assuntos
Ivermectina/administração & dosagem , Ivermectina/toxicidade , Ivermectina/uso terapêutico , Complicações na Gravidez/induzido quimicamente , Gestantes , Teratogênios/toxicidade , Administração Oral , Adulto , Feminino , Humanos , Gravidez , Resultado da Gravidez
19.
Environ Pollut ; 257: 113618, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784274

RESUMO

Pesticides pollution has caused serious environmental problems in recent years, and mounting evidence has shown that more and more insecticides have serious risk in human health. Emamectin Benzoate formally regarded as a highly safety insecticide based on its exclusive targets, but the cytotoxicity to human lung was ignored for a long time. In the present study, bioassay experiments were used to assess the toxicity of the Emamectin Benzoatein on human non-target cells including cell viability assay, DNA damage assay, flow cytometer assay and western blotting assay. The results indicated that Emamectin Benzoatecan cause the inhibition of the proliferation, cytochrome c release, activation of caspase-3/9 and increase Bax/Bcl-2 ratio, which means it induced the cytotoxicity on 16HBE cells associated with the mitochondrial apoptosis. Besides, the DNA damge caused by the Emamectin Benzoate suggest it has a potential genotoxic effect on human lung cells.


Assuntos
Inseticidas/toxicidade , Ivermectina/análogos & derivados , Testes de Toxicidade , Brônquios , Humanos , Ivermectina/toxicidade
20.
Ecotoxicol Environ Saf ; 188: 109889, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704331

RESUMO

It is known that abamectin (ABM) inflicts oxidative damage on aquatic animals; however, knowledge about the immune response under pesticide-induced oxidative stress is incomplete. In the present study, several cellular and humoral immune parameters, including total haemocyte counts (THC), lysosomal membrane stability (LMS), activities of acid phosphatase (ACP), alkaline phosphatase (AKP) and lysozyme (LZM) were investigated to reveal the effects of ABM exposure on the immune defence mechanisms of the important freshwater crab, Erocheir sinensis. According to the results, a significant increase of THC was found in low concentration groups (0.03 and 0.06 mg/L), while dramatic decreases occurred in high concentration groups (0.12 and 0.24 mg/L) after 96 h of exposure. We also detected significant increases of reactive oxygen species (ROS) in haemocytes at 0.12 and 0.24 mg/L, and there was a dose- and time-dependent decrease of lysosomal membrane stability. These results suggest that the excessive generation of ROS induced by ABM may be leading the massive collapse of lysosomal membrane, which in turn may be causing the sharp drop of haemocyte counts in E. sinensis. The increase of hydrolytic enzymes ACP and AKP at low concentrations and the decrease at high concentrations also indicate an immune response associated with haemocytes status under stress. However, activities of LZM decreased significantly. After injection of Aeromonas hydrophil, mortalities increased under exposure to ABM and were positively related to ABM concentration. These results confirm that ABM exposure has the ability to impair immune defence and result in the host's susceptibility to pathogens.


Assuntos
Braquiúros/imunologia , Inseticidas/toxicidade , Ivermectina/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Braquiúros/efeitos dos fármacos , Braquiúros/metabolismo , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Hemócitos/patologia , Imunidade Inata/efeitos dos fármacos , Ivermectina/toxicidade , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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