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1.
PLoS One ; 17(4): e0265962, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35390011

RESUMO

Current USEPA ecological risk assessments for pesticide registration include a determination of potential risks to bees. Toxicity data are submitted to support these assessments and the USEPA maintains a large database containing acute and chronic toxicity data on adult and larval honey bees (Apis mellifera), which USEPA considers a surrogate for Apis and non-Apis bees. We compared these toxicity data to explore possible trends. This analysis indicated a significant correlation between acute contact and oral median lethal dose (LD50) values for adult honey bees (ρ = 0.74, p <0.0001). Using default EPA modeling assumptions, where exposure for an individual bee is roughly 12x lower through contact than through ingestion, the analysis indicates that the oral LD50 is similarly if not more protective of the contact LD50 for the majority of pesticides and modes of action evaluated. The analysis also provided evidence that compounds with a lower acute toxicity for adults through contact and oral exposure pathways may still be acutely toxic for larvae. The acute toxicity of herbicides and fungicides was higher for larvae relative to oral and contact toxicity for adult honey bees for the same compounds and the no observed adverse effect level (NOAEL) from chronic toxicity studies were lower for larvae relative to adults, indicating increased sensitivity of larvae. When comparing 8-day LD50 values between single dose larval acute studies to those derived from repeat dose 22-day larval chronic toxicity studies, the LD50 values derived from chronic studies were significantly lower than those from acute toxicity tests (Z = -37, p = 0.03).


Assuntos
Praguicidas , Animais , Abelhas , Larva , Dose Letal Mediana , Praguicidas/toxicidade , Estudos Retrospectivos , Testes de Toxicidade Aguda
2.
Int J Mol Sci ; 23(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35269835

RESUMO

The radioprotective effects of a new 1-isobutanoil-2-isopropylisothiourea derivative named T1082 are presented. Research methods included toxic characteristics, radioprotective activity (Till-McCulloch's test and 30-day survival test) in γ-ray total-body-irradiated mice, and a clinical and histological study of the effect of T1082 on acute radiation skin reactions (RSR) in rats after a single or fractionated ß-ray local irradiation. T1082 is more effective than its analogue, the NOS inhibitor T1023, at low concentrations and doses (1/12-1/8 LD10), both parenterally and intragastrically. In this case, its therapeutic index (LD50/ED50) reaches 30, and the optimal radioprotective doses (ED84-98-141-224 mg/kg) are an order less than the maximum tolerated doses-1/16-1/10 LD10. These properties allowed T1082, at a low intragastrical dose (160 mg/kg; 1/14 LD10), to significantly limit the severity of acute RSR after single (40 Gy) and fractionated (78 Gy) ß-ray irradiation. The results confirm T1082 as one of the safest emergency radioprotectors and indicate the prospects for its further development as a pharmacological agent for the prevention of RT complications.


Assuntos
Proteção Radiológica , Protetores contra Radiação , Animais , Raios gama , Dose Letal Mediana , Camundongos , Fosfatos , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Ratos
3.
Proc Natl Acad Sci U S A ; 119(11): e2109667119, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35275791

RESUMO

SignificanceYersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. This plague bacillus has been used as a biological weapon during human history and is currently one of the deadliest biological threats. Currently, no licensed plague vaccines are available in the Western world. Since an array of immunogens are enclosed in outer membrane vesicles (OMVs), immune responses elicited by OMVs against a diverse range of antigens may reduce the likelihood of antigen circumvention. Therefore, self-adjuvanting OMVs from a remodeled Yersinia pseudotuberculosis strain as a type of plague vaccine could diversify prophylactic choices and solve current vaccine limitations.


Assuntos
Antígenos de Bactérias , Lipídeo A , Vacina contra a Peste , Peste , Proteínas Citotóxicas Formadoras de Poros , Yersinia pseudotuberculosis , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Dose Letal Mediana , Lipídeo A/genética , Lipídeo A/imunologia , Camundongos , Peste/prevenção & controle , Vacina contra a Peste/administração & dosagem , Vacina contra a Peste/genética , Vacina contra a Peste/imunologia , Plasmídeos/genética , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/imunologia , Yersinia pseudotuberculosis/genética , Yersinia pseudotuberculosis/imunologia
4.
Molecules ; 27(5)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35268738

RESUMO

A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and ß-sitosterol (4).


Assuntos
Artemisia/química , Proteases 3C de Coronavírus/antagonistas & inibidores , Flavonoides/química , SARS-CoV-2/enzimologia , Animais , Artemisia/metabolismo , Sítios de Ligação , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico , Proteases 3C de Coronavírus/metabolismo , Teoria da Densidade Funcional , Flavonoides/isolamento & purificação , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Dose Letal Mediana , Masculino , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ratos , SARS-CoV-2/isolamento & purificação , Pele/efeitos dos fármacos , Pele/patologia
5.
Biomed Res Int ; 2022: 1040129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35211622

RESUMO

BACKGROUND: Traditional Chinese medicine Yinhuapinggan granule (YHPG) has been used for treating upper respiratory tract infection like influenza, cough, and viral pneumonia. However, its active ingredients that really exert the main efficacy have not been well elucidated. This study is aimed at screening its antiviral components and investigating the potential therapeutic mechanisms of YHPG against the influenza A/PR8/34 (H1N1) virus in Madin Darby canine kidney (MDCK). METHODS: MDCK cells were infected with the influenza virus and then treated with ribavirin, YHPG, and main active ingredients in YHPG. Based on the maximum nontoxic concentration (TC0), half-maximal toxic concentration (TC50), half-maximal inhibitory concentration (IC50), and therapeutic index (TI), interferon-ß (IFN-ß) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the gene expression of TLR7, MyD88, tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Jun amino terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and p65 nuclear transcription factor-kappa B (p65 NF-κB) was quantified using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The results indicated that the components of YHPG, such as ephedrine hydrochloride, pseudoephedrine hydrochloride, chlorogenic acid, and emodin, had significant antiviral effects. High and medium doses of YHPG effectively reduced the cytopathic effect (CPE) and significantly decreased IFN-ß and IL-6 levels in the supernatant. Simultaneously, the transcript levels of TLR7, MyD88, TRAF6, JNK, p38 MAPK, and p65 NF-κB decreased in infected MDCK cells. Moreover, a certain dose-dependent relationship among different groups of YHPG was observed. CONCLUSIONS: These results indicated that YHPG and the components of YHPG had a significant inhibitory function on the proliferation of the H1N1 virus. The mechanism might be associated with suppressing the activation of the TLR7/MyD88 signaling pathway, a decrease in the mRNA expression of key target genes, and inhibition of IFN-ß and IL-6 secretion.


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Animais , Cães , Interferon beta/metabolismo , Interleucina-6/metabolismo , Dose Letal Mediana , Células Madin Darby de Rim Canino , Medicina Tradicional Chinesa , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Ribavirina/farmacologia , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 7 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo
6.
Sci Rep ; 12(1): 2277, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35145175

RESUMO

Botanical insecticides are preferred for their environment and user-friendly nature. Eugenol is a plant-based monoterpene having multifarious biocidal activities. To understand whether eugenol would persistently work against Aedes aegypti, we performed larvicidal bioassays on thirty successive generations and determined median lethal concentration (LC50) on each generation. Results showed no apparent differences between LC50 at F0 (63.48 ppm) and F30 (64.50 ppm) indicating no alteration of susceptibility toward eugenol. To analyze, if eugenol has any effect on metabolic detoxification-associated enzymes, we measured esterases (alpha and beta), cytochrome P450, and GST activities from the survived larvae exposed to LC50 concentration from F0-F30. Results revealed a decrease of esterases, GST, and cytochrome P450 activities at the initial 4-8 generations and then a gradual increase as the generations progressed. GST activity remained significantly below the control groups. Synergists (TPP, DEM, and PBO) were applied along with eugenol at F30 and LC50 concentration, and the said enzyme activities were recorded. Results showed a noticeable decrease in LC50 and enzyme activities indicating effective inhibitions of the respective enzymes. Overall, present results inferred that eugenol would effectively work as a larvicide for a longer period in successive generations without initiating rapid resistance and therefore could be advocated for controlling A. aegypti.


Assuntos
Aedes/efeitos dos fármacos , Eugenol/farmacologia , Inseticidas , Larva/efeitos dos fármacos , Aedes/embriologia , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Esterases/metabolismo , Glutationa Transferase/metabolismo , Larva/enzimologia , Dose Letal Mediana
7.
Sci Rep ; 12(1): 1975, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35132122

RESUMO

Aphelenchoides besseyi could cause great yield losses of rice and many economically important crops. Acetylcholinesterase (AChE) inhibitors were commonly used to manage plant-parasitic nematodes. However, nematodes resistant to AChE inhibitors have been increasingly reported due to the extensive use of these chemicals. The current study was aimed to establish the correlation between fenamiphos (an AChE-inhibitor) sensitivities and acetylcholinesterase genes (ace) by analyzing two isolates of A. besseyi (designated Rl and HSF), which displayed differential sensitivities to fenamiphos. The concentrations of fenamiphos that led to the death of 50% (LD50) of Rl and HSF were 572.2 ppm and 129.4 ppm, respectively. Three ace genes were cloned from A. besseyi and sequenced. Sequence searching and phylogenic analyses revealed that AChEs of R1 and HSF shared strong similarities with those of various vertebrate and invertebrate species. Molecular docking analysis indicated that AChEs-HSF had much higher affinities to fenamiphos than AChEs-R1. Quantitative reverse transcriptase-PCR analyses revealed that expression of three ace genes were downregulated in HSF but were upregulated in Rl after exposure to 100 ppm fenamiphos for 12 h. The results indicated that the expression of the ace genes was modulated in response to fenamiphos in different nematode strains. An increased expression of the ace genes might contribute to fenamiphos-insensitivity as seen in the Rl isolate.


Assuntos
Acetilcolinesterase/genética , Inibidores da Colinesterase/farmacologia , Expressão Gênica , Nematoides/efeitos dos fármacos , Nematoides/genética , Compostos Organofosforados/farmacologia , Acetilcolinesterase/metabolismo , Animais , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Dose Letal Mediana , Simulação de Acoplamento Molecular , Regulação para Cima/efeitos dos fármacos
8.
PLoS One ; 17(2): e0263677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35143580

RESUMO

Spodoptera frugiperda (J.E. Smith) is a highly invasive noctuid pest first reported in northern Australia during early 2020. To document current status of resistance in S. frugiperda in Australia, insecticide toxicity was tested in field populations collected during the first year of establishment, between March 2020 and March 2021. Dose-response was measured by larval bioassay in 11 populations of S. frugiperda and a susceptible laboratory strain of Helicoverpa armigera. Emamectin benzoate was the most efficacious insecticide (LC50 0.023µg/ml) followed by chlorantraniliprole (LC50 0.055µg/ml), spinetoram (LC50 0.098µg/ml), spinosad (LC50 0.526µg/ml), and methoxyfenozide (1.413µg/ml). Indoxacarb was the least toxic selective insecticide on S. frugiperda (LC50 3.789µg/ml). Emamectin benzoate, chlorantraniliprole and methoxyfenozide were 2- to 7-fold less toxic on S. frugiperda compared with H. armigera while spinosyns were equally toxic on both species. Indoxacarb was 28-fold less toxic on S. frugiperda compared with H. armigera. There was decreased sensitivity to Group 1 insecticides and synthetic pyrethroids in S. frugiperda compared with H. armigera: toxicity was reduced up to 11-fold for methomyl, 56 to 199-fold for cyhalothrin, and 44 to 132-fold for alpha cypermethrin. Synergism bioassays with metabolic inhibitors suggest involvement of mixed function oxidase in pyrethroid resistance. Recommended diagnostic doses for emamectin benzoate, chlorantraniliprole, spinetoram, spinosad, methoxyfenozide and indoxacarb are 0.19, 1.0, 0.75, 6, 12 and 48µg/µl, respectively.


Assuntos
Resistência a Inseticidas , Inseticidas/toxicidade , Oxigenases de Função Mista/metabolismo , Spodoptera/crescimento & desenvolvimento , Animais , Austrália , Combinação de Medicamentos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hidrazinas/toxicidade , Proteínas de Insetos/metabolismo , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Hormônios Juvenis/toxicidade , Larva/efeitos dos fármacos , Larva/enzimologia , Larva/crescimento & desenvolvimento , Dose Letal Mediana , Macrolídeos/toxicidade , Oxazinas/toxicidade , Vigilância da População , Spodoptera/efeitos dos fármacos , Spodoptera/enzimologia , ortoaminobenzoatos/toxicidade
9.
Mar Drugs ; 20(2)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35200611

RESUMO

Palytoxin (PLTX) is a highly toxic polyether identified in various marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. In addition to adverse effects in humans, negative impacts on different marine organisms have been often described during Ostreopsis blooms and the concomitant presence of PLTX and its analogues. Considering the increasing frequency of Ostreopsis blooms due to global warming, PLTX was investigated for its effects on Artemia franciscana, a crustacean commonly used as a model organism for ecotoxicological studies. At concentrations comparable to those detected in culture media of O. cf. ovata (1.0-10.0 nM), PLTX significantly reduced cysts hatching and induced significant mortality of the organisms, both at larval and adult stages. Adults appeared to be the most sensitive developmental stage to PLTX: significant mortality was recorded after only 12 h of exposure to PLTX concentrations > 1.0 nM, with a 50% lethal concentration (LC50) of 2.3 nM (95% confidence interval = 1.2-4.7 nM). The toxic effects of PLTX toward A. franciscana adults seem to involve oxidative stress induction. Indeed, the toxin significantly increased ROS levels and altered the activity of the major antioxidant enzymes, in particular catalase and peroxidase, and marginally glutathione-S-transferase and superoxide dismutase. On the whole, these results indicate that environmentally relevant concentrations of PLTX could have a negative effect on Artemia franciscana population, suggesting its potential ecotoxicological impact at the marine level.


Assuntos
Acrilamidas/toxicidade , Artemia/efeitos dos fármacos , Venenos de Cnidários/toxicidade , Toxinas Marinhas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Acrilamidas/administração & dosagem , Animais , Venenos de Cnidários/administração & dosagem , Relação Dose-Resposta a Droga , Ecotoxicologia , Dose Letal Mediana , Estágios do Ciclo de Vida , Toxinas Marinhas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
10.
Arch Toxicol ; 96(3): 817-830, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35034154

RESUMO

There exists consensus that the traditional means by which safety of chemicals is assessed-namely through reliance upon apical outcomes obtained following in vivo testing-is increasingly unfit for purpose. Whilst efforts in development of suitable alternatives continue, few have achieved levels of robustness required for regulatory acceptance. An array of "new approach methodologies" (NAM) for determining toxic effect, spanning in vitro and in silico spheres, have by now emerged. It has been suggested, intuitively, that combining data obtained from across these sources might serve to enhance overall confidence in derived judgment. This concept may be formalised in the "tiered assessment" approach, whereby evidence gathered through a sequential NAM testing strategy is exploited so to infer the properties of a compound of interest. Our intention has been to provide an illustration of how such a scheme might be developed and applied within a practical setting-adopting for this purpose the endpoint of rat acute oral lethality. Bayesian statistical inference is drawn upon to enable quantification of degree of confidence that a substance might ultimately belong to one of five LD50-associated toxicity categories. Informing this is evidence acquired both from existing in silico and in vitro resources, alongside a purposely-constructed random forest model and structural alert set. Results indicate that the combination of in silico methodologies provides moderately conservative estimations of hazard, conducive for application in safety assessment, and for which levels of certainty are defined. Accordingly, scope for potential extension of approach to further toxicological endpoints is demonstrated.


Assuntos
Medição de Risco/métodos , Testes de Toxicidade Aguda/métodos , Toxicologia/métodos , Animais , Teorema de Bayes , Segurança Química/métodos , Simulação por Computador , Dose Letal Mediana , Ratos
11.
J Fluoresc ; 32(1): 397-404, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34977993

RESUMO

Reported here is a new [Cu4I4] cluster-based coordination polymer, namely [Cu4I4(bib)2]n·n(DMF) (1, bib = 1,4-bis(imidazolyl)butane, DMF = N,N'-dimethylformamide), which was synthesized by the self-assemble reaction of CuI, bib and KI under solvothermal conditions. Remarkably, compound 1 shows promising photocatalytic performance toward to the degradation of MB solution under visible light irradiation. For the COPD treatment, the ELISA detection kit was conducted to determine the content of INF-γ released by the respiratory tract mucosal epithelial cells. In addition to this, the activation levels of the NF-κB signaling pathway were still need to be assessed by the real time RT-PCR after the compound treatment.


Assuntos
Cobre/química , Cobre/farmacologia , Interferon gama/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Animais , Catálise , Células Epiteliais/metabolismo , Humanos , Dose Letal Mediana , Camundongos , NF-kappa B/metabolismo , Processos Fotoquímicos , Polímeros , Reação em Cadeia da Polimerase em Tempo Real , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Transdução de Sinais , Difração de Raios X
12.
BMC Complement Med Ther ; 22(1): 16, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031035

RESUMO

BACKGROUND: Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. METHODS: Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals' relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. RESULTS: There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats' relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium's inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. CONCLUSION: The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.


Assuntos
Aloe/toxicidade , Extratos Vegetais/toxicidade , Animais , Feminino , Dose Letal Mediana , Masculino , Ratos , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Uganda
13.
J Agric Food Chem ; 70(4): 1079-1089, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35060723

RESUMO

The golden apple snail Pomacea canaliculata is an invasive pest that causes extensive damage to agricultural production. P. canaliculata is also an intermediate host of Angiostrongylus cantonensis, which causes human eosinophilic meningitis. In this study, the molluscicidal activity and safety profile of a novel molluscicide PBQ [1-(4-chlorophenyl)-3-(pyridin-3-yl)urea] were evaluated. PBQ exhibited strong molluscicidal potency against adult and juvenile snails (LC50 values of 0.39 and 0.07 mg/L, respectively). In field trials, PBQ killed 99.42% of the snails at 0.25 g a.i./m2. An acute toxicity test in rats demonstrated that PBQ is a generally nonhazardous chemical. PBQ is also generally safe for nontarget organisms including Brachydanio rerio, Daphnia magna, and Apis mellifera L. Transcriptomics analysis revealed that PBQ had a significant impact on the carbohydrate and lipid metabolism pathways, which provided insights into its molluscicidal mechanism. These results suggest that PBQ could be developed as an effective and safe molluscicide for P. canaliculata control.


Assuntos
Angiostrongylus cantonensis , Moluscocidas , Infecções por Strongylida , Animais , Dose Letal Mediana , Moluscocidas/toxicidade , Ratos , Caramujos
14.
Pest Manag Sci ; 78(4): 1657-1664, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34989113

RESUMO

BACKGROUND: The white garden snail, Theba pisana, is distributed worldwide and is a serious molluscan pest of different crops. Emamectin benzoate (EMB) 'an avermectin derivative' is a novel biorational agent and highly effective pesticide. This study focused on the lethal and in vivo sublethal toxic effect of EMB on the energy reserves (glycogen, lipids and proteins), total energy reserves and activities of glutathione S-transferase (GST), γ-glutamyl transferase (γ-GT), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the hepatopancreas of T. pisana for up to 7 days of exposure. RESULTS: The median lethal dose (LD50 ) at 48 h of EMB treatment was 5.34 µg g-1 body weight (b.w.). Sublethal doses of 1.07 and 3.20 µg g-1 b.w. (i.e., 20% and 60% of the LD50 ) led to significant dose- and time-dependent decreases in glycogen and lipids; these doses increased the total protein level. Overall, the tested sublethal doses significantly decreased the total energy reserves. Moreover, GST and γ-GT activities were elevated, whereas the activities of AST and ALT were inhibited in the exposed snails. A decrease in LDH activity after 1 and 3 days of exposure and an increase after 7 days of exposure were seen in snails treated with EMB. CONCLUSION: EMB exerted lethal toxicity on T. pisana and consequently caused changes in energy reserve levels and enzyme activities in the animal. © 2022 Society of Chemical Industry.


Assuntos
Moluscocidas , Animais , Glutationa Transferase/metabolismo , Ivermectina/análogos & derivados , Dose Letal Mediana , Moluscocidas/toxicidade , Caramujos
15.
BMC Pharmacol Toxicol ; 23(1): 3, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983670

RESUMO

BACKGROUND: Up-and-down procedure (UDP) was recommended to replace traditional acute toxicity methods. However, it was limited due to the long experimental period (20-42 days). To improve UDP, an improved UDP method (iUDP) was developed by shortening observation time between sequence dosages. The aim of this study was to test the reliability of iUDP to provide a reliable method for the acute toxicity measurement of valuable or minor amount compounds. METHODS: Oral median lethal dose (LD50) of nicotine, sinomenine hydrochloride and berberine hydrochloride were measured both by iUDP and modified Karber method (mKM). RESULTS: LD50 of the three alkaloids measured by iUDP with 23 mice were 32.71 ± 7.46, 453.54 ± 104.59, 2954.93 ± 794.88 mg/kg, respectively. LD50 of the three alkaloids measured by mKM with 240 mice were 22.99 ± 3.01, 456.56 ± 53.38, 2825.53 ± 1212.92 mg/kg, respectively. The average time consumed by the two methods were 22 days and 14 days respectively. Total grams of the alkaloids used by the two methods were 0.0082 and 0.0673 (nicotine), 0.114 and 1.24 (sinomenine hydrochloride), 1.9 and 12.7 (berberine hydrochloride). CONCLUSION: iUDP could replace mKM to detect acute toxicity of substances with comparable and reliable result. And it is suitable for valuable or minor amount substances.


Assuntos
Alcaloides , Alcaloides/toxicidade , Animais , Dose Letal Mediana , Camundongos , Reprodutibilidade dos Testes
16.
BMC Pharmacol Toxicol ; 23(1): 2, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983673

RESUMO

BACKGROUND: Py-mulin is a new pleuromutilin derivative with potent antibacterial activities in vitro and in vivo, suggesting this compound may lead to a promising antibacterial drug after further development. The present study is aimed to evaluate the acute and subacute oral toxicity, and the genotoxicity with the standard Ames test according to standard protocols. METHODS: Acute oral toxicity of Py-mulin was determined using Kunming mice. The 28-day repeated dose oral toxicity study in SD rats was performed according to OECD guideline No. 407. The bacterial reverse mutation (Ames test) was carried out using four Salmonella typhimurium (S. typhimurium) strains TA97, TA98, TA100 and TA1535 with and without S9 metabolic activation. RESULTS: The LD50 values in acute oral toxicity were 2973 mg/kg (female mice) and 3891 mg/kg (male mice) calculated by the Bliss method. In subacute toxicity study, 50 mg/kg Py-mulin did not induce any abnormality in body weight, food consumption, clinical sign, hematology, clinical chemistry, organ weight, and histopathology in all of the treatment groups. However, high doses of Py-mulin (100 and 300 mg/kg) displayed slightly hepatotoxicity to female rats. Furthermore, Py-mulin did not significantly increase the number of revertant colonies of four standard S. typhimurium strains with the doses of 0.16-1000 µg/plate in the Ames study. CONCLUSIONS: Based on our findings, our study provides some information for the safety profile of Py-mulin.


Assuntos
Antibacterianos , Salmonella typhimurium , Animais , Antibacterianos/toxicidade , Feminino , Dose Letal Mediana , Masculino , Camundongos , Testes de Mutagenicidade/métodos , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/genética
17.
Environ Pollut ; 297: 118786, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34990738

RESUMO

Polyhalogenated polycyclic aromatic hydrocarbons (HPAHs) represent a major environmental concern due to their persistency and toxicity. Among them, mono-halogenated (HNs) and halomethyl naphthalenes (HMNs) are not well-studied, and the toxicity of many HNs to fishes has not been reported. In this study, we exposed zebrafish (Danio rerio) embryos to naphthalene and five HNs at concentrations ranging from 0.25 to 2.0 mg L-1 to assess acute toxicities and developmental effects. Among them, 2-bromomethyl naphthalene (2-BMN) produced moderate lethal effects (96-h LC50 = 1.4 mg L-1) and significantly reduced hatchability. Abnormal phenotypes, including pericardial edema, spine curvature, and shortened body length, were also induced by 2-BMN (96-h EC50 = 0.45 mg L-1). Treatments of 0.5-2.0 mg L-1 2-BMN evoked cardiac malformations via significant down-regulation of the cacna1c gene, which codes the voltage-dependent calcium channel, at 72 hpf and up-regulation of the nppa gene, responsible for the expression of natriuretic peptides, at 96 hpf in zebrafish. One presumable toxic photo-dissociated metabolite of 2-BMN, the 2-naphthylmethyl radical, may be responsible for the toxic effect on zebrafish embryos. HPAHs must be monitored and managed due to their adverse effects on living organisms at low concentrations.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Embrião não Mamífero , Dose Letal Mediana , Naftalenos/toxicidade , Poluentes Químicos da Água/toxicidade
18.
Parasit Vectors ; 15(1): 2, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980219

RESUMO

BACKGROUND: Odorant-binding proteins (OBPs) play important roles in many physiological processes of mosquitoes. Previous high-throughput sequencing studies have revealed that some OBPs of Culex quinquefasciatus might be involved in the development of resistance to insecticides. METHODS: Based on the results of sequencing analyses, the OBP28 gene was selected for evaluation in this study. Three laboratory strains of Cx. quinquefasciatus [susceptible strain (SS), deltamethrin-resistant strain 1 (HN) and deltamethrin-resistant strain 2 (RR)] were first examined by using the Centers for Disease Control and Prevention bottle bioassay, after which the expression level of the OBP28 gene in the susceptible and deltamethrin-resistant strains was determined by real-time quantitative polymerase chain reaction. The OBP28 gene in deltamethrin-resistant strain RR was silenced using RNA interference technology. The expression level of OBP28 and the resistance level were tested in the silenced strain and control strain after microinjection of double-stranded RNA for a 48-h interference period. Four field-collected strains (henceforth 'field strains') of Cx. quinquefasciatus were also examined for their resistance to deltamethrin and levels of OBP28 expression. Finally, a correlation analysis between deltamethrin resistance and gene expression was carried out for all seven strains, i.e. the four field strains and the three laboratory strains. RESULTS: In the bioassay, the mortality of SS, HN and RR was 100%, 21.33% and 1.67%, respectively. The relative expression levels of OBP28 in strains HN and RR were 6.30- and 6.86-fold higher, respectively, than that of strain SS. After silencing of the OBP28 gene, the mortality of strain RR was 72.20% and that of the control strain 26.32%. The mortality of strain RR increased significantly after interference compared to that of the control strain. There was a negative correlation between OBP28 gene expression and mortality in adult mosquitoes after exposure to deltamethrin. CONCLUSIONS: To our knowledge, this study shows for the first time a correlation between the expression of a gene coding for OBP and insecticide resistance in mosquitoes. The potential resistance mechanism that was elucidated provides a new target gene for the surveillance of resistance in mosquitoes.


Assuntos
Culex/metabolismo , Resistência a Inseticidas/fisiologia , Inseticidas/metabolismo , Nitrilas/metabolismo , Piretrinas/metabolismo , Receptores Odorantes/metabolismo , Animais , Bioensaio , Culex/classificação , DNA/biossíntese , DNA/química , Feminino , Dose Letal Mediana , RNA/genética , RNA/isolamento & purificação , Interferência de RNA/fisiologia , RNA de Cadeia Dupla/biossíntese , RNA de Cadeia Dupla/farmacologia
19.
Parasit Vectors ; 15(1): 35, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35073988

RESUMO

Dose-response relationships reflect the effects of a substance on organisms, and are widely used in broad research areas, from medicine and physiology, to vector control and pest management in agronomy. Furthermore, reporting on the response of organisms to stressors is an essential component of many public policies (e.g. public health, environment), and assessment of xenobiotic responses is an integral part of World Health Organization recommendations. Building upon an R script that we previously made available, and considering its popularity, we have now developed a software package in the R environment, BioRssay, to efficiently analyze dose-response relationships. It has more user-friendly functions and more flexibility, and proposes an easy interpretation of the results. The functions in the BioRssay package are built on robust statistical analyses to compare the dose/exposure-response of various bioassays and effectively visualize them in probit-graphs.


Assuntos
Bioensaio/estatística & dados numéricos , Bioestatística , Software , Animais , Bioestatística/instrumentação , Bioestatística/métodos , Relação Dose-Resposta a Droga , Humanos , Dose Letal Mediana , Saúde Pública/estatística & dados numéricos
20.
Molecules ; 27(2)2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35056874

RESUMO

Heavy metals intoxication causes several health problems that necessitate finding new protective and therapeutic approaches. This study aimed to evaluate the impact of Musa sp. leaves extract (MLE) on hepato-renal toxicities induced by cadmium (Cd) in male mice. The phytochemical screening, metal chelating activity (MCA), and the median lethal dose (LD50) of MLE were determined. Fifty CD-1 male mice were used and intraperitoneally (i.p.) injected with MLE (1000 to 5000 mg/kg b.wt) for MLE LD50 determination. Another 50 mice were used for evaluating the effect of MLE on Cd toxicity. Blood samples were collected for hematological, liver, and kidney functions assessments. Liver tissue homogenates were used for determination of oxidant/antioxidant parameters. Liver and kidney tissues were harvested for histopathological and molecular investigations. MLE showed potent in vitro antioxidant activities. The MCA and LD50 of the MLE were 75 µg/mL and 3000 mg/kg b.wt, respectively. MLE showed beneficial therapeutic activity against hepato-renal toxicities in Cd-intoxicated mice, evidenced by improving the hematological, biochemical, histopathological, and molecular alterations.


Assuntos
Antioxidantes/farmacologia , Quelantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Nefropatias/prevenção & controle , Musa/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Contagem de Células Sanguíneas , Cádmio/toxicidade , Intoxicação por Cádmio/prevenção & controle , Quelantes/química , Quelantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Enzimas/metabolismo , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/patologia , Dose Letal Mediana , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
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