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1.
J Agric Food Chem ; 68(50): 14824-14831, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33322905

RESUMO

Soil-borne pathogens and weeds could synergistically affect vegetable growth and result in serious losses. The investigation of antagonistic metabolites from a marine-derived entomopathogenic fungus, Beauveria felina, obtained polyhydroxy steroid (1), tricyclic diterpenoid (2), isaridin (3), and destruxin cyclodepsipeptides (4-6). The structures and absolute configurations of new 1-3 were elucidated by extensive spectroscopic and X-ray crystallographic analyses, as well as electronic circular dichroism (ECD) calculations. Compounds 1 and 2 showed antifungal activities against carbendazim-resistant strains of Botrytis cinerea, with the minimum inhibitory concentration (MIC) values ranging from 16 to 32 µg/mL, which were significantly better than those of carbendazim (MIC = 256 µg/mL). Compound 5 exhibited significant antagonistic activity against the radicle growth of Amaranthus retroflexus seedlings, which was almost identical to that of the positive control (2,4-dichlorophenoxyacetic acid). The structure-activity differences of 4-6 suggested that the Cl atom in HMPA1 and ß-Me in Pro2 should be the key factors to their herbicidal activities. Besides, compounds 3-6 showed moderate nematicidal activities against Meloidogyne incognita. These antagonistic effects of 1-6 were first reported and further revealed the synergistically antagonistic potential of B. felina to be developed into the biopesticide.


Assuntos
Antifúngicos/farmacologia , Antinematódeos/farmacologia , Beauveria/química , Beauveria/metabolismo , Animais , Antifúngicos/química , Antifúngicos/metabolismo , Antinematódeos/química , Antinematódeos/metabolismo , Beauveria/isolamento & purificação , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Cristalografia por Raios X , Depsipeptídeos/química , Depsipeptídeos/metabolismo , Depsipeptídeos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Água do Mar/microbiologia , Metabolismo Secundário , Tylenchoidea/efeitos dos fármacos , Tylenchoidea/crescimento & desenvolvimento
2.
PLoS One ; 15(10): e0239993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022025

RESUMO

A two-year field trial was conducted in a vineyard (northern Egypt)cultivated with Thompson seedless grapevines to evaluate the effectiveness of four "alternative" (biological/chemical) treatments, Bacillus megaterium, boric acid, calcium nitrate and chitosan, against the root-knot nematode Meloidogyne incognita (Mi), compared to that of the nematicide oxamyl. The influence of these treatments on plant nutritional status and fruit yield and quality was also assessed. All treatments significantly inhibited Mi reproduction parameters in both seasons, decreasing the numbers of nematode galls and egg masses (roots) and of second-stage juveniles (soil). Oxamyl application resulted in the highest reductions in Mi-reproduction parameters, followed by boric acid, which also showed the highest relative nematicidal efficacy (respect to oxamyl). In the 1st season, the highest fruit yield (10.34 kg/grapevine) was recorded from boric acid-treated plants, followed by that from oxamyl-treated plants (7.50 kg/grapevine); in the subsequent season (2019), oxamyl use led to the highest yield, followed by boric acid + chitosan use (10.04 and 8.62 kg/grapevine, respectively). In both seasons, application of boric acid alone and combined with chitosan enhanced the total soluble solids (TSS)/total acidity ratio in grape juice. All treatments led to higher nutrient contents (leaf petioles) and chlorophyll levels (leaves) as well as enhanced fruit size and weight. We conclude that the tested treatments can be safely applied for nematode management in Thompson seedless grapevines, with positive effects on fruit yield and quality.


Assuntos
Estado Nutricional , Controle da População/métodos , Tylenchoidea/fisiologia , Vitis/crescimento & desenvolvimento , Animais , Antinematódeos/farmacologia , Ácidos Bóricos/farmacologia , Carbamatos/farmacologia , Quitosana/farmacologia , Clorofila/análise , Egito , Frutas/efeitos dos fármacos , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Sucos de Frutas e Vegetais/análise , Estado Nutricional/efeitos dos fármacos , Estações do Ano , Tylenchoidea/efeitos dos fármacos , Vitis/efeitos dos fármacos , Vitis/metabolismo
3.
Rev Bras Parasitol Vet ; 29(3): e003820, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027421

RESUMO

Semi-intensive equine breeding system favors gastrointestinal nematode infections. The treatment of these infections is based on the use of anthelmintics. However, the inappropriate use of these drugs has led to parasitic resistance to the available active principles. The objective of this study was to evaluate the efficacy of the main classes of antiparasitic (ATP) used in control in adult and young animals, including: benzimidazoles (fenbendazole), pyrimidines (pyrantel pamoate), macrocyclic lactones (ivermectin and moxidectin), as well as the combination of active ingredients (ivermectin + pyrantel pamoate). The study was carried out in two military establishments, located in Rio Grande do Sul (RS), from January to December, 2018. The intervals between the treatments of the animals were performed from 30 to 90 days. Coproparasitological evaluations were determined by the egg count reduction in the faeces. Cyatostomine larvae were identified in pre and post-treatment cultures. The results demonstrated the multiple parasitic resistance of cyathostomins to fenbendazole, moxidectin in young animals, and to fenbendazole, pyrantel pamoate in adult animals. Thus, it is necessary to define or diagnose parasitic resistance to assist in the creation of prophylactic parasitic control, using suppressive treatment with ATP associated with integrated alternatives. The progress of parasitic resistance can be slowed.


Assuntos
Antinematódeos , Resistência a Múltiplos Medicamentos , Militares , Infecções Equinas por Strongyloidea , Estrongilídios , Animais , Antinematódeos/farmacologia , Antinematódeos/uso terapêutico , Brasil , Fezes/parasitologia , Cavalos , Larva/efeitos dos fármacos , Contagem de Ovos de Parasitas/veterinária , Infecções Equinas por Strongyloidea/tratamento farmacológico , Infecções Equinas por Strongyloidea/parasitologia , Estrongilídios/efeitos dos fármacos
4.
J Vet Sci ; 21(5): e72, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33016019

RESUMO

BACKGROUND: Fenbendazole, a dewormer drug, is used widely in the clinical treatment of parasite infections in animals. Recent studies have shown that fenbendazole has substantial effects on tumor growth, immune responses, and inflammatory responses, suggesting that fenbendazole is a pluripotent drug. Nevertheless, the antiviral effects have not been reported. Fenbendazole can disrupt microtubules, which are essential for multiple viruses infections, suggesting that fenbendazole might have antiviral effects. OBJECTIVES: This study examined whether fenbendazole could inhibit bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures. METHODS: The effects of fenbendazole on viral production, transcription of the immediate early (IE) genes, viron-associated protein expression, and the cellular signaling PLC-γ1/Akt pathway were assessed using distinct methods. RESULTS: Fenbendazole could inhibit BoHV-1 productive infections significantly in MDBK cells in a dose-dependent manner. A time-of-addition assay indicated that fenbendazole affected both the early and late stages in the virus replication cycles. The transcription of IE genes, including BoHV-1 infected cell protein 0 (bICP0), bCP4, and bICP22, as well as the synthesis of viron-associated proteins, were disrupted differentially by the fenbendazole treatment. The treatment did not affect the cellular signaling pathway of PLC-γ1/Akt, a known cascade playing important roles in virus infection. CONCLUSIONS: Overall, fenbendazole has antiviral effects on BoHV-1 replication.


Assuntos
Antivirais/farmacologia , Fenbendazol/farmacologia , Herpesvirus Bovino 1/efeitos dos fármacos , Animais , Antinematódeos/farmacologia , Cães , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Células Madin Darby de Rim Canino
5.
Exp Parasitol ; 218: 107982, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866584

RESUMO

Ancylostoma caninum is a gastrointestinal parasite that affect dogs and humans, considered a worldwide public health problem. The control of these parasitosis is increasingly difficult due to the development of multi-drug resistance. Bacillus thuringiensis is an insecticidal, spore forming bacterium, often species specific. The strain GP526 of B. thuringiensis has toxic effect on the cestode Dipylidium caninum and the trematode Centrocestus formosanus, both of them zoonotic parasites. The high degrees of specificity and environment safe make B. thuringiensis suitable for use against pathogen parasites, especially those resistant to synthetic chemical insecticides. The objective of the current work was to evaluate the in vitro effect of B. thuringiensis on Ancylostoma caninum. Spore-crystal mixture of the strains was co-incubated with 120 adult nematodes (males, non-pregnant females and pregnant females) or with 4800 eggs. GP526 showed a nematicidal effect with an LT50 of 35.8 h and an LC50 of 60 µg/ml. It also showed an ovicidal effect with an LC50 of 94.9 µg/ml. Histological analyses showed detachment of the cuticle and of the uterus in adult females, and vacuolization with destruction of the eggs. The effects of GP526 strain were comparable to those of albendazole, allowing us to propose GP526 for A. caninum control, in both, the adult stage at a gastrointestinal level, and in egg stage in the environment. In addition, GP526 can be proposed as a potential broad spectrum antiparasitic drug.


Assuntos
Ancylostoma/microbiologia , Ancilostomíase/prevenção & controle , Bacillus thuringiensis/fisiologia , Zoonoses/parasitologia , Albendazol/farmacologia , Albendazol/uso terapêutico , Ancylostoma/efeitos dos fármacos , Animais , Antinematódeos/farmacologia , Antinematódeos/uso terapêutico , Bacillus thuringiensis/química , Proteínas de Bactérias/análise , Doenças do Cão/parasitologia , Cães , Eletroforese em Gel de Poliacrilamida , Feminino , Dose Letal Mediana , Masculino , Controle Biológico de Vetores/métodos , Zoonoses/prevenção & controle
6.
PLoS One ; 15(8): e0237150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760111

RESUMO

Prevention of canine heartworm disease caused by Dirofilaria immitis relies on chemoprophylaxis with macrocyclic lactone anthelmintics. Alarmingly, there are increased reports of D. immitis isolates with resistance to macrocyclic lactones and the ability to break through prophylaxis. Yet, there is not a well-established laboratory assay that can utilize biochemical phenotypes of microfilariae to predict drug resistance status. In this study we evaluated laboratory assays measuring cell permeability, metabolism, and P-glycoprotein-mediated efflux. Our assays revealed that trypan blue, propidium iodide staining, and resazurin metabolism could detect differences among D. immitis isolates but none of these approaches could accurately predict drug susceptibility status for all resistant isolates tested. P-glycoprotein assays suggested that the repertoire of P-gp expression is likely to vary among isolates, and investigation of pharmacological differences among different P-gp genes is warranted. Further research is needed to investigate and optimize laboratory assays for D. immitis microfilariae, and caution should be applied when adapting cell death assays to drug screening studies for nematode parasites.


Assuntos
Antinematódeos/farmacologia , Dirofilaria immitis/efeitos dos fármacos , Ivermectina/farmacologia , Macrolídeos/farmacologia , Fenótipo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Células Cultivadas , Dirofilaria immitis/metabolismo , Dirofilaria immitis/patogenicidade , Dirofilariose/parasitologia , Cães , Resistência a Medicamentos , Proteínas de Helminto/metabolismo
7.
Nat Commun ; 11(1): 2858, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504051

RESUMO

Metastatic melanoma is challenging to manage. Although targeted- and immune therapies have extended survival, most patients experience therapy resistance. The adaptability of melanoma cells in nutrient- and therapeutically-challenged environments distinguishes melanoma as an ideal model for investigating therapy resistance. In this review, we discuss the current available repertoire of melanoma models including two- and three-dimensional tissue cultures, organoids, genetically engineered mice and patient-derived xenograft. In particular, we highlight how each system recapitulates different features of melanoma adaptability and can be used to better understand melanoma development, progression and therapy resistance.


Assuntos
Antinematódeos/farmacologia , Modelos Animais de Doenças , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Antinematódeos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Camundongos , Camundongos Transgênicos , Organoides , Pele/citologia , Pele/imunologia , Pele/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Esferoides Celulares
8.
Parasitol Res ; 119(10): 3369-3376, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32556502

RESUMO

Toxocara canis is a common parasite of dogs and can cause zoonotic toxocariasis in humans. As a part of control programs for this agent, optimized hygiene including chemical disinfection is considered essential in the prevention and control of zoonotic toxocariasis in humans. However, commonly used disinfectants at present mostly fail to inhibit the embryogenesis and viability of T. canis eggs. To this effect, the present study was designed to evaluate the effect of a chlorocresol-based disinfectant product Neopredisan®135-1 (NP) on embryonic development of T. canis eggs in vitro and to investigate the infectivity of exposed eggs by assessing larval establishment in a mouse model. Under in vitro conditions, NP at a final concentration of 0.25, 0.50, 1, 2, or 4% all exhibited significant killing effect on T. canis embryogenesis compared with the control eggs (P < 0.05), regardless of contact times (30, 60, 90, or 120 min). Such killing activity increased in a concentration- and time-dependent manner, with a maximum killing efficacy of 95.81% at 4% concentration and 120 min exposure time. Comparisons between low and high concentrations and between short and long contact times concluded that a protocol using the 1% concentration of NP with a 90-min contact could be the most suitable for practical application. Additionally, the lower larval recovery in mice inoculated with eggs treated by either 0.25 or 0.5% NP than that from their corresponding controls (P < 0.05) verified once again that NP had an adverse impact on the larval development of T. canis eggs even at a low concentration. To the best of our knowledge, this is the first study to report the effect of the chlorocresol-based disinfectant NP on the embryonation and larval development of T. canis eggs, and the results presented here would contribute to environmental clearance and control of toxocariasis by providing an alternative disinfectant resource. However, it is highlighted that the clearance of the novel and existing sources of infection including larvated eggs in places treated with NP is not guaranteed and therefore continuous monitoring and additional disinfection are still required.


Assuntos
Antinematódeos/farmacologia , Cresóis/farmacologia , Desinfetantes/farmacologia , Toxocara canis/efeitos dos fármacos , Toxocaríase/prevenção & controle , Animais , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Camundongos , Óvulo/efeitos dos fármacos , Óvulo/crescimento & desenvolvimento , Carga Parasitária , Toxocara canis/crescimento & desenvolvimento , Toxocaríase/parasitologia
9.
PLoS Pathog ; 16(4): e1008396, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32243475

RESUMO

Nematode parasites infect approximately 1.5 billion people globally and are a significant public health concern. There is an accepted need for new, more effective anthelmintic drugs. Nicotinic acetylcholine receptors on parasite nerve and somatic muscle are targets of the cholinomimetic anthelmintics, while glutamate-gated chloride channels in the pharynx of the nematode are affected by the avermectins. Here we describe a novel nicotinic acetylcholine receptor on the nematode pharynx that is a potential new drug target. This homomeric receptor is comprised of five non-α EAT-2 subunits and is not sensitive to existing cholinomimetic anthelmintics. We found that EAT-18, a novel auxiliary subunit protein, is essential for functional expression of the receptor. EAT-18 directly interacts with the mature receptor, and different homologs alter the pharmacological properties. Thus we have described not only a novel potential drug target but also a new type of obligate auxiliary protein for nAChRs.


Assuntos
Antinematódeos/farmacologia , Ascaris suum/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Helminto/metabolismo , Faringe/metabolismo , Receptores Nicotínicos/metabolismo , Acetilcolina/farmacologia , Animais , Ascaris suum/efeitos dos fármacos , Ascaris suum/genética , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Helminto/genética , Faringe/efeitos dos fármacos , Receptores Nicotínicos/genética
10.
Vet Parasitol ; 280: 109088, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32278938

RESUMO

Chicory (Cichorium intybus) is a bioactive forage rich in sesquiterpene lactones (SLs) with reported in vitro and in vivo anthelmintic activity in livestock. However, the on-farm adoption of chicory as an anthelmintic crop is limited and may be facilitated by using standardised industrial chicory material. Chicory root pulp is a by-product obtained from industrial chicory roots after inulin extraction and can potentially retain SLs. However, SL content and associated anthelmintic activity of chicory root pulp have not been investigated. Here, we evaluated the anthelmintic activity of SL-enriched extracts from chicory root pulp and forage chicory, and used untargeted metabolomics and molecular networking to identify potential anthelmintic molecules. Six different sources of chicory material were used: fresh chicory root pulp (from industrial chicory roots C. intybus var. sativum; "Root Pulp"), fresh leaves from chicory cv. Spadona (sampled on four occasions) and fresh leaves from chicory cv. Choice. The resulting extracts were tested for anthelmintic activity against the free-living nematode Caenorhabditis elegans and the pig nematode Ascaris suum. The cytotoxicity of the chicory extracts was evaluated on mammalian (Vero) cells. In the C. elegans assays, the Root Pulp was the most potent extract and induced paralysis in >95% of worms exposed to >250  µg extract/mL (EC50 = 64.2 µg/mL). In the A. suum assays, the Root Pulp was also the most potent chicory extract to inhibit worm motility (EC50 = 87.6  µg/mL), followed closely by two of the Spadona leaf extracts (EC50 = 89.8  µg/mL and 112.2  µg/mL) The Root Pulp extract had the lowest cytotoxicity of all tested extracts towards mammalian cells, with a selectivity index of 5.37. Untargeted metabolomics revealed that chicory Root Pulp had a markedly different chemical profile in comparison with forage chicory extracts. Molecular networking confirmed several SLs and SL-derivatives mainly present in chicory root pulp, that may be responsible of its potent anti-parasitic activity. Bioactivity-based molecular networking of chicory root pulp and the most potent forage chicory extracts revealed a high predicted anthelmintic score for the guaianolide SL 11,13-dihydro-lactucopicrin. In conclusion, chicory root pulp showed potent and selective in vitro anthelmintic activity against C. elegans and A. suum, with low cytotoxicity in mammalian cells. The promising anthelmintic activity of chicory root pulp should be confirmed in vivo to further explore the potential of this agro-industrial by-product as a nutraceutical anthelmintic for livestock and as novel source of anti-parasitic compounds.


Assuntos
Antinematódeos/farmacologia , Ascaris suum/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Chicória/química , Resíduos Industriais/análise , Metaboloma , Animais , Chlorocebus aethiops , Metabolômica , Células Vero
11.
J Helminthol ; 94: e135, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32127057

RESUMO

Haemonchus contortus is a haematophagous gastrointestinal nematode (GIN) that causes severe anaemia and even death in small ruminants, negatively impacting the economic viability of farms. Traditionally, this parasite has been controlled with chemical compounds; however, inadequate use of these types of products has favoured the emergence of anthelmintic resistance. Therefore, it is necessary to search for alternatives for GIN control. Previous studies have reported the anthelmintic activity of edible mushroom extracts against H. contortus. A recent study reported that a fraction constituted of different fatty acids and ß-sitosterol isolated from the basidiomata of the edible mushroom Pleurotus djamor ECS-123 has ovicidal and larvicidal activity against H. contortus. Thus, this study aimed to assess the anthelmintic activity of the pure molecules: pentadecanoic acid, palmitic acid, ß-sitosterol, stearic acid and linoleic acid. For this purpose, an egg-hatching inhibition test was carried out in which the compounds were evaluated individually and in combination at a final concentration of 20 mg mL-1. Furthermore, larval mortality was assessed using a combination of the five commercial compounds previously mentioned at different concentrations (1.25-20 mg mL-1). Palmitic acid and stearic acid, in some combinations, inhibited H. contortus egg hatching by 100%. On the other hand, in the larval mortality test, the combination of the five compounds showed dose-dependent behaviour, and 100% mortality was obtained 24 h post-incubation. Pure molecules and their combinations have anthelmintic-like activity against the eggs and larvae of H. contortus.


Assuntos
Antinematódeos/farmacologia , Ácidos Graxos/farmacologia , Haemonchus/efeitos dos fármacos , Sitosteroides/farmacologia , Agaricales/química , Animais , Bioensaio , Ácidos Graxos/química , Ácidos Graxos/classificação , Trato Gastrointestinal/parasitologia , Larva/efeitos dos fármacos , Masculino , Extratos Vegetais/farmacologia , Ovinos/parasitologia
12.
Molecules ; 25(3)2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32050419

RESUMO

Root-knot nematode diseases cause severe yield and economic losses each year in global agricultural production. Virgibacillus dokdonensis MCCC 1A00493, a deep-sea bacterium, shows a significant nematicidal activity against Meloidogyne incognita in vitro. However, information about the active substances of V. dokdonensis MCCC 1A00493 is limited. In this study, volatile organic compounds (VOCs) from V. dokdonensis MCCC 1A00493 were isolated and analyzed through solid-phase microextraction and gas chromatography-mass spectrometry. Four VOCs, namely, acetaldehyde, dimethyl disulfide, ethylbenzene, and 2-butanone, were identified, and their nematicidal activities were evaluated. The four VOCs had a variety of active modes on M. incognita juveniles. Acetaldehyde had direct contact killing, fumigation, and attraction activities; dimethyl disulfide had direct contact killing and attraction activities; ethylbenzene had an attraction activity; and 2-butanone had a repellent activity. Only acetaldehyde had a fumigant activity to inhibit egg hatching. Combining this fumigant activity against eggs and juveniles could be an effective strategy to control the different developmental stages of M. incognita. The combination of direct contact and attraction activities could also establish trapping and killing strategies against root-knot nematodes. Considering all nematicidal modes or strategies, we could use V. dokdonensis MCCC 1A00493 to set up an integrated strategy to control root-knot nematodes.


Assuntos
Antinematódeos/isolamento & purificação , Doenças das Plantas/prevenção & controle , Tylenchoidea/efeitos dos fármacos , Virgibacillus/química , Compostos Orgânicos Voláteis/isolamento & purificação , Acetaldeído/isolamento & purificação , Acetaldeído/farmacologia , Animais , Antinematódeos/farmacologia , Organismos Aquáticos , Derivados de Benzeno/isolamento & purificação , Derivados de Benzeno/farmacologia , Butanonas/isolamento & purificação , Butanonas/farmacologia , Quimiotaxia/efeitos dos fármacos , Dissulfetos/isolamento & purificação , Dissulfetos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/parasitologia , Contagem de Ovos de Parasitas , Doenças das Plantas/parasitologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/parasitologia , Microextração em Fase Sólida , Tylenchoidea/crescimento & desenvolvimento , Compostos Orgânicos Voláteis/farmacologia
13.
Vet Parasitol ; 278: 109031, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32032866

RESUMO

The neuromuscular system of parasitic nematodes has proven to be an efficient pharmacological target for antihelmintics. Some of the most frequently used antiparasitic drugs are agonists or antagonists of nicotinic acetylcholine receptors (nAChRs). The antinematodal mechanism of action of carvacrol involves the inhibition of parasite muscle contraction. We have examined the interaction of carvacrol with antinematodal drugs that are agonists of different subtypes of nAChRs and monepantel, which is a non-competitive antagonist of this receptor in A. suum. Additionally, we investigated the effect of carvacrol on the muscle type of nAChRs in the mammalian host. As orthosteric agonists of nAChR, pyrantel, morantel and befinijum lead to dose-dependent contractions of the neuromuscular preparation of Ascaris suum. Carvacrol 100 µM decreased the Emax of pyrantel, morantel and bephenium by 29%, 39% and 12 %, 39 % and 12 % respectively. The EC50 ratio was 3.43, 2.95 and 2.47 for pyrantel, morantel and bephinium, respectively. Carvacrol 300 u µM reduces the Emax of pyrantel, morantel and bephenium by 71%, 80% and 75 %, 80 % and 75 % respectively. The EC50 ratio for pyrantel, morantel and bephenium was 3.88, 3.19 and 4.83 respectively. Furthermore, carvacrol enhances the inhibitory effect of monepantel on A. suum contractions, which may have an effective clinical application. On the other hand, tested concentrations of carvacrol did not significantly affect the EFS-induced contractions of the rat diaphragm, indicating a lack of interaction with the postsynaptic nAChR at the muscle end plate in mammals, but the highest concentration (300 µM) caused a clear tetanic fade. Carvacrol exhibited a time and dose-dependent effect on the Rota-rod performances of rats with a high value of the ED50 (421.6 mg/kg). In our research, carvacrol dominantly exhibited characteristics of a non-competitive antagonist of nAChR in A. suum, and enhances the inhibitory effect of monepantel. The combination of monepantel and carvacrol may be clinically very effective, and the carvacrol molecule itself can be used as a promising platform for the development of new anthelmintic drugs.


Assuntos
Aminoacetonitrila/análogos & derivados , Antinematódeos/farmacologia , Ascaris suum/efeitos dos fármacos , Cimenos/farmacologia , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Aminoacetonitrila/farmacologia , Animais , Sistema Nervoso Central/efeitos dos fármacos , Diafragma/efeitos dos fármacos , Feminino , Músculos/efeitos dos fármacos , Ratos
14.
Vet Parasitol ; 279: 109010, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035291

RESUMO

In a context of nematodicidal resistance, anthelmintic combinations have emerged as a reliable pharmacological strategy to control gastrointestinal nematodes in grazing systems of livestock production. The current work evaluated the potential drug-drug interactions following the coadministration of two macrocyclic lactones (ML) ivermectin (IVM) and abamectin (ABM) to parasitized cattle using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The kinetic behavior of both compounds administered either separately or coadministered was assessed and the therapeutic response of the combination was evaluated under different resistance scenarios. In the pharmacological trial, calves received a single subcutaneous (s.c.) injection of IVM (100 µg/Kg); a single s.c. injection of ABM (100 µg/Kg) or IVM + ABM (50 µg/Kg each) administered in different injection sites to reach a final ML dose of 100 µg/Kg (Farm 1). Plasma samples were taken from those animals up to 20 days post-treatment. IVM and ABM plasma concentrations were quantified by HPLC. A parasitological trial was carried out in three farms with different status of nematodes resistance to IVM. Experimental animals received IVM (200 µg/Kg), ABM (200 µg/Kg) or IVM + ABM (100 µg/Kg each) in Farm 2, and IVM + ABM (200 µg/Kg each) in Farms 3 and 4. The anthelmintic efficacy was determined by fecal egg count reduction test (FECRT). PK analysis showed similar trends for IVM kinetic behavior after coadministration with ABM. Conversely, the ABM elimination half-life was prolonged and the systemic exposure during the elimination phase was increased in the presence of IVM. Although IVM alone failed to control Cooperia spp., the combination IVM + ABM was the only treatment that achieved an efficacy higher than 95% against resistant Cooperia spp. in all farms. In fact, when Cooperia spp. was the main genus within the nematode population and Haemonchus spp. was susceptible or slightly resistant to ML (Farms 2 and 4), the total FECR for the combination IVM + ABM was higher than 90%. Instead, when the predominant nematode genus was a highly resistant Haemonchus spp. (Farm 3), the total FECR after the combined treatment was as low as the single treatments. Therefore, the rational use of these pharmacological tools should be mainly based on the knowledge of the epidemiology and the nematode susceptibility status in each cattle farm.


Assuntos
Antinematódeos/farmacologia , Doenças dos Bovinos/tratamento farmacológico , Haemonchus/efeitos dos fármacos , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Rabditídios/efeitos dos fármacos , Animais , Antinematódeos/farmacocinética , Bovinos , Interações Medicamentosas , Hemoncose/tratamento farmacológico , Hemoncose/veterinária , Ivermectina/farmacocinética , Masculino , Distribuição Aleatória , Infecções por Rhabditida/tratamento farmacológico , Infecções por Rhabditida/veterinária
15.
J Helminthol ; 94: e130, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103787

RESUMO

In a previous research work aimed at discovering natural helminthicides as alternatives to conventional synthetic drugs, Piper retrofractum fruit hexane extract (PHE) has been shown to possess promising nematocidal activity against the third-stage infective larvae of Strongyloides stercoralis. Thus, this study was designed to evaluate the chemical composition and the impact of PHE on symptom and structural alterations of S. stercoralis. Chemical analysis of PHE by gas chromatography-mass spectrometry demonstrated 26 different compounds, constituting 100% of the total composition. The main components were 4-acetylphenyl (4-benzoylphenoxy) acetate (14.86%) and octyl methoxycinnamate (12.72%). Nematocidal bioassays revealed promising potential of PHE against S. stercoralis larvae, with an LC50 value of 0.059 mg/ml, while the reference drug ivermectin exerted higher efficacy, with an LC50 value of 0.020 µg/ml. Behavioural observations under light microscopy revealed that PHE-treated S. stercoralis larvae moved slowly, became paralysed and eventually died during 24 h of incubation. The dead larvae appeared under light microscope as straight worms with unknown vacuoles of different sizes inside their internal bodies. Morphological alterations of the PHE-treated S. stercoralis larvae, such as straight bodies with swollen cuticle, faded transverse annulations and faded longitudinal striations, as well as shallow and smooth lateral longitudinal grooves, were seen clearly under scanning electron microscopy. Ultrastructural changes in the treated larvae, such as protruded lateral longitudinal grooves, loose muscle with vacuolation, dissociation between the hypodermis and cuticle and marked intracellular disorganization with vacuolation, were detected under transmission electron microscopy. The results of this study provide evidence that PHE is toxic against S. stercoralis and also a potential new alternative for anti-Strongyloides chemotherapy.


Assuntos
Antinematódeos/farmacologia , Larva/efeitos dos fármacos , Larva/ultraestrutura , Piper/química , Extratos Vegetais/farmacologia , Strongyloides stercoralis/efeitos dos fármacos , Animais , Cromatografia Gasosa , Frutas/química , Ivermectina/farmacologia , Larva/anatomia & histologia , Espectrometria de Massas , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Strongyloides stercoralis/ultraestrutura
16.
PLoS One ; 15(1): e0216688, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31931510

RESUMO

The root-knot nematode Meloidogyne incognita has a wide host range and it is one of the most economically important crop parasites worldwide. Biological control has been a good approach for reducing M. incognita infection, for which many nematophagous fungi are reportedly applicable. However, the controlling effects of Phanerochaete chrysosporium strain B-22 are still unclear. In the present study we characterized the parasitism of this strain on M. incognita eggs, second-stage juveniles (J2), and adult females. The highest corrected mortality was 71.9% at 3 × 108 colony forming units (CFU) mL-1 and the estimated median lethal concentration of the fungus was 0.96 × 108 CFU mL-1. Two days after treatment with Phanerochaete chrysosporium strain B-22 eggshells were dissolved. A strong lethal effect was noted against J2, as the fungal spores developed in their body walls, germinated, and the resulting hyphae crossed the juvenile cuticle to dissolve it, thereby causing shrinkage and deformation of the juvenile body wall. The spores and hyphae also attacked adult females, causing the shrinkage and dissolution of their bodies and leakage of contents after five days. Greenhouse experiments revealed that different concentrations of the fungal spores effectively controlled M. incognita. In the roots, the highest inhibition rate for adult females, juveniles, egg mass, and gall index was 84.61%, 78.91%, 84.25%, and 79.48%, respectively. The highest juvenile inhibition rate was 89.18% in the soil. Phanerochaete chrysosporium strain B-22 also improved tomato plant growth, therefore being safe for tomato plants while effectively parasitizing M. incognita. This strain is thus a promising biocontrol agent against M. incognita.


Assuntos
Phanerochaete/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Tylenchoidea/microbiologia , Animais , Antinematódeos/farmacologia , Feminino , Interações Hospedeiro-Parasita/efeitos dos fármacos , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Hifas/patogenicidade , Phanerochaete/efeitos dos fármacos , Phanerochaete/patogenicidade , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia
17.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936073

RESUMO

Gastrointestinal strongyle nematodes (GIS) are included among the most important parasites of small ruminants. The widespread drug resistance and drug residues in products of animal origin have increased the interest in the search for natural compounds with anthelmintic activity as a valid alternative to current synthetic drugs. The aim of the present investigation was to test the 'in vitro' anthelmintic activity of saponins and prosapogenins from different Medicago species, selected for their importance as a forage crop worldwide for animal feeding. From these plants, saponin mixtures were extracted, purified and used at scalar concentrations to evaluate their anthelmintic activities against sheep gastrointestinal strongyles (GISs), by the egg hatch test. Treated and untreated controls were used as the comparison. Data were statistically analyzed, and EC50 and EC90 were also calculated. All saponins and prosapogenins showed inhibiting effects on GIS eggs in a concentration-dependent manner. At higher concentrations, most of them showed an efficacy comparable to the reference drug (Thiabendazole 3 µg/mL) (P < 0.001). With 1.72 mg/mL EC50 and 3.84 mg/mL EC90, saponin from M. polymorpha cultivars Anglona was the most active. Obtained results encourage further studies aimed at evaluating the efficacy 'in vivo' of saponins which resulted as most effective 'in vitro' in this study.


Assuntos
Antinematódeos/farmacologia , Trato Gastrointestinal/parasitologia , Medicago/química , Saponinas/farmacologia , Animais , Fezes/parasitologia , Nematoides/efeitos dos fármacos , Nematoides/crescimento & desenvolvimento , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Saponinas/química , Ovinos
18.
PLoS One ; 15(1): e0227448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31899763

RESUMO

Third-stage larvae (L3) of Steinernema feltiae exist as free-living infective juveniles (IJ), with suspended development activities. In contrast, parasitic stages (L1, L2, L4, adult) have mutualistic relations with Xenorhabdus species bacteria, along with unique morphological changes and development inside the cadaver of host insects and/or plant-parasitic nematodes. Commercial IJ strains are tolerant to cucurbitacin-containing phytonematicides, but we have scant information on how morphological adjustments in IJ are achieved. In this study, we investigated the nature of morphological adjustments in commercial S. feltiae IJ strains to Nemafric-BL phytonematicide, which contains cucurbitacin B as active ingredient. Post-72 h exposure to phytonematicide concentration, IJ specimens were fixed on mounting slides. Length (body, excretory pore to anterior end, pharynx, rectum, stoma, tail), diameter (head width, neck base, mid-body, anal body), cuticle thickness and De Man ratios were measured with a computer software programme attached to Omax light microscope. Morphometric data against increasing phytonematicide concentration exhibited either density-dependent quadratic, linear or neutral relations. Increase in body length at low phytonematicide concentration was accompanied by decrease in tail length and pharynx length during muscle contraction when IJ were still alive. After death at high phytonematicide concentration, the opposite morphometric effects ensued due to muscle relaxation. The observed changes in morphometric structures were explained on the basis of morphological adjustments that modulated volumes of pseudocoelom cavity in IJ. The modulation is intended to maintain hydrostatic pressure within permissible upper limits in order to avoid structural damage to internal organs embedded in the pseudocoelom fluids.


Assuntos
Antinematódeos/química , Rabditídios/fisiologia , Animais , Antinematódeos/metabolismo , Antinematódeos/farmacologia , Tamanho Corporal/efeitos dos fármacos , Larva/anatomia & histologia , Larva/efeitos dos fármacos , Larva/fisiologia , Microscopia , Rabditídios/efeitos dos fármacos , Rabditídios/crescimento & desenvolvimento , Simbiose , Triterpenos/farmacologia , Xenorhabdus/fisiologia
19.
N Z Vet J ; 68(3): 187-192, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31778612

RESUMO

ABSTRACTAims: The main goal of the current study was to evaluate, on a commercial beef cattle farm, the impact of infection with gastrointestinal nematodes resistant to both ivermectin (IVM) and moxidectin (MXD) on the productivity of calves.Methods: Male Aberdeen Angus calves, aged 9-11 months, with faecal nematode egg counts (FEC) ≥200 epg and body weight ≥190 kg, were allocated to two herds. Herd A (n = 90) grazed a maize-winter forage crop rotation and Herd B (n = 90) grazed a 2-year-old Agropyrum pasture. On Day 0 in each herd, calves were randomly allocated into five groups (n = 18), which were treated with 0.2 mg/kg IVM; 0.2 mg/kg MXD; 3.75 mg/kg ricobendazole (RBZ), both IVM and RBZ, or remained untreated. Faecal samples collected on Days -1 and 19 were used to determine the percentage reduction in FEC, and genera of the nematodes were determined by the identification of the third-stage larvae recovered from faecal cultures. Total weight gain was determined from body weights recorded on Days -1 and 91.Results: Overall mean reduction in FEC was 42% for IVM, 67% for MXD, 97% for RBZ and 99% for IVM + RBZ. The reduction in FEC for Cooperia spp. was ≤78% for IVM and MXD, and for Haemonchus spp. was 0 and 36% for IVM and MXD, respectively, confirming the presence of parasites resistant to both anthelmintics. Only IVM + RBZ treatment resulted in 100% efficacy against Haemonchus spp. The overall estimated mean total weight gain for calves treated with IVM was 15.7 (95% CI = 11.9-19.7) kg and for calves treated with IVM + RBZ was 28.8 (95% CI = 25-32.5) kg (p < 0.001). Mean total weight gain for calves treated with MXD was 23.5 (95% CI = 19.7-27.2) kg.Conclusions and clinical relevance: In calves naturally infected with resistant nematodes, under the production system assessed here, weight gains were lower in calves treated with anthelmintics that were moderately or highly ineffective compared to those treated with highly effective anthelmintics. These results demonstrate to farmers and veterinarians the importance of a sustainable and effective nematode control under field conditions.


Assuntos
Albendazol/análogos & derivados , Antiparasitários/farmacologia , Doenças dos Bovinos/tratamento farmacológico , Ivermectina/farmacologia , Macrolídeos/farmacologia , Infecções por Nematoides/veterinária , Albendazol/farmacologia , Animais , Anti-Helmínticos/farmacologia , Antinematódeos/farmacologia , Argentina , Peso Corporal/efeitos dos fármacos , Bovinos , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/fisiopatologia , Resistência a Múltiplos Medicamentos , Quimioterapia Combinada/veterinária , Masculino , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/fisiopatologia , Contagem de Ovos de Parasitas/veterinária , Carne Vermelha
20.
J Asian Nat Prod Res ; 22(12): 1197-1206, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31773971

RESUMO

Gramine can be intelligently and efficiently supplied with N, N-dimethylamino group and then reacted with the corresponding sulfonyl chlorides to synthesize N, N-dimethylarylsulfonamides. We herein designed and controlled synthesis of N, N-dimethylarylsulfonamide derivatives, and first reported the results of the nematicidal activity of 15 title compounds 3a-o against Meloidogyne incongnita in vitro, respectively. Among all of the title derivatives, compounds 3a, 3c, 3k, and 3o exhibited potent nematicidal activity with median lethal concentration (LC50) values ranging from 0.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-methoxyphenylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide (3o) showed the best promising and pronounced nematicidal activity, with LC50 values of 0.2381 and 0.2259 mg/L, respectively.


Assuntos
Antinematódeos , Tylenchoidea , Animais , Antinematódeos/farmacologia , Estrutura Molecular
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