RESUMO
Cyathostomins are the largest group of parasites in horses that can be controlled by ivermectin (IVM). This study aimed to run a four-dose titration trial of IVM in 28 naturally infected Thoroughbred yearlings. The local Strongyle population had been recorded to be resistant to IVM (200 µg/kg). The parasite fecal egg count (FEC) was performed to investigate the egg reappearance period (ERP) of two and five weeks (w2pt and w5pt) after IVM treatment. FEC was > 1000 on day zero for all groups. Although 100% FEC reduction was reported at w2pt for all concentrations, the FEC at w5pt revealed < 83% efficacy. This study reports the reduction of ERP using the label dose as well as 300, and 400 µg/kg (double dose) of IVM. The protocol allowed IVM to significantly suppress FEC w2pt although not eliminating adult worms, failing to guarantee an extension of its protection period over 8 weeks. Moreover, the FEC at w5pt possibly means the infection was not cleared, and worms reestablished egg laying. We raised the possibility of withdrawing IVM of control programs when the drug has less than 80% FEC reduction at w5pt.
Assuntos
Ivermectina , Contagem de Ovos de Parasitas , Animais , Ivermectina/uso terapêutico , Ivermectina/administração & dosagem , Cavalos/parasitologia , Brasil , Doenças dos Cavalos/parasitologia , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/diagnóstico , Feminino , Antiparasitários/uso terapêutico , Antiparasitários/administração & dosagem , Infecções Equinas por Strongyloidea/tratamento farmacológico , Infecções Equinas por Strongyloidea/parasitologia , Infecções Equinas por Strongyloidea/diagnóstico , Fezes/parasitologiaRESUMO
Fluazuron is a novel veterinary pour-on antitick formulation which can be applied simultaneously with bovine reproduction management strategies. Considering the economic importance of the livestock industry in many countries, it is important to know whether antiparasitics such as fluazuron may cause embryonic loss. The aim of this study was to evaluate the toxicological effect of fluazuron on bovine oocytes during in vitro maturation. The best fluazuron concentrations were determined in a preliminary experiment on Chinese hamster ovary (CHO)-K1 cells and further used to compare fluazuron toxicity in both study models. Results of the annexin V and alkaline single cell gel electrophoresis assays demonstrated that fluazuron caused cytotoxicity and genotoxicity in bovine cumulus cells at all the concentrations tested (50, 75 and 100 µg fluazuron/mL). The evaluation of cortical granules and mitochondria distribution showed that cytoplasmic maturation was not affected by fluazuron treatment. However, a decrease in metaphase II + polar body, degenerate oocytes as well as disorganized chromatin in polar body were observed at all concentrations tested. Whereas the fertilization process was not altered by 50 µg/mL fluazuron, the embryo development rate decreased significantly. No significant differences were observed in any of the oxidative stress parameters assessed. This study contributes to a better understanding of fluazuron in bovines, suggesting that the antiparasitic may affect bovine reproduction and might cause embryo loss.
Assuntos
Técnicas de Maturação in Vitro de Oócitos , Oócitos , Compostos de Fenilureia , Animais , Bovinos , Oócitos/efeitos dos fármacos , Compostos de Fenilureia/farmacologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Células CHO , Cricetulus , Antiparasitários/farmacologia , Antiparasitários/toxicidade , FemininoRESUMO
Ivermectin (IVM) is a widely used antiparasitic. Concerns have been raised about its environmental effects in the wetlands of Río de la Plata basin where cattle have been treated with IVM for years. This study investigated the sublethal effects of environmentally relevant IVM concentrations in sediments on the Neotropical fish Prochilodus lineatus. Juvenile P. lineatus were exposed to IVM-spiked sediments (2 and 20 µg/Kg) for 14 days, alongside a control sediment treatment without IVM. Biochemical and oxidative stress responses were assessed in brain, gills, and liver tissues, including lipid damage, glutathione levels, enzyme activities, and antioxidant competence. Muscle and brain acetylcholinesterase activity (AChE) and stable isotopes of 13C and 15N in muscle were also measured. The lowest IVM treatment resulted in an increase in brain lipid peroxidation, as measured by thiobarbituric acid reactive substances (TBARs), decreased levels of reduced glutathione (GSH) in gills and liver, increased catalase activity (CAT) in the liver, and decreased antioxidant capacity against peroxyl radicals (ACAP) in gills and liver. The highest IVM treatment significantly reduced GSH in the liver. Muscle (AChE) was decreased in both treatments. Multivariate analysis showed significant overall effects in the liver tissue, followed by gills and brain. These findings demonstrate the sublethal effects of IVM in P. lineatus, emphasizing the importance of considering sediment contamination and trophic habits in realistic exposure scenarios.
Assuntos
Antiparasitários , Ivermectina , Poluentes Químicos da Água , Animais , Ivermectina/toxicidade , Antiparasitários/toxicidade , Poluentes Químicos da Água/toxicidade , Gado , América do Sul , Estresse Oxidativo/efeitos dos fármacos , Sedimentos Geológicos/química , Brânquias/efeitos dos fármacos , Brânquias/metabolismoRESUMO
Ivermectin (IVM) is a broad-spectrum veterinary antiparasitic used worldwide in cattle breeding. The aim of this study was to evaluate the lethal effects of the active ingredient and a commercial formulation of IVM (1 % active ingredient) in the embryonic stage (S. 4-6) and larval stage (S. 25) of the South American amphibian Rhinella arenarum through chronic standardized bioassays. Also, behavior analysis and oxidative stress and cholinergic effects biomarkers were analyzed at 1, 10 and 100 µg IVM/L concentrations. For the embryonic stage, the active ingredient (96 h- LC50: 15900 µg/L) was more toxic than the commercial formulation (96 h-LC50: 51230 µg/L) during the acute period, while at chronic exposure the commercial formulation was more toxic (504 h-LC50: 10.25 µg/L), compared to the active ingredient (504 h-LC50: 312.80 µg/L). For the larval stage, in acute exposure, the active ingredient (96 h-LC50: 800 µg/L) was more toxic than the commercial formulation (96 h-LC50: 1550 µg/L). In the chronic exposure, the commercial formulation (504 h-LC50: 77.33 µg/L) was more toxic than the active ingredient (504 h-LC50: 195.25 µg/L). Overall, larvae exhibited greater sensitivity to both the active ingredient and the commercial formulation. However, during chronic exposure, embryos were more sensitive to the commercial formulation than larvae. The commercial formulation primarily induced oxidative stress, and both forms of the compound affected behavior and cholinergic effect biomarkers, even at low environmentally relevant concentrations (1 µg/L). These results highlight the potential impact of IVM on aquatic ecosystems.
Assuntos
Ivermectina , Larva , Estresse Oxidativo , Poluentes Químicos da Água , Animais , Ivermectina/toxicidade , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Larva/efeitos dos fármacos , Antiparasitários/toxicidade , Bufonidae , Dose Letal Mediana , Ecotoxicologia , Embrião não Mamífero/efeitos dos fármacosRESUMO
The ivermectin (IVM), as a broad-spectrum antiparasitic drug, was widely prescribed to treat COVID-19 during the pandemic, despite lacking proven efficacy in combating this disease. Therefore, it is important to establish affordable devices in laboratories with minimal infrastructure. The laser engraving technology has been revolutionary in sensor manufacturing, primarily attributed to the diversity of substrates that can be employed and the freedom it provides in creating sensor models. In this work, electrochemical sensors based on graphene were developed using the laser engraving technology for IVM sensing. Through, the studies that used the techniques of cyclic voltammetry and differential pulse voltammetry, following parameter optimization, for the laser-induced graphene electrode demonstrated a mass transport governed by adsorption of the species and exhibited a linear working range of 10-100 (µmol L-1), a limit of detection (LOD) of 1.6 × 10-6 (mol L-1), a limit of quantification (LOQ) of 4.8 × 10-6 (mol L-1), and a sensitivity of 0.139 (µA µmol L-1). The developed method was successfully applied to direct analysis of pharmaceutical tablets, tap water (recovery of 94%) and synthetic urine samples (recovery between 97% and 113%). These results demonstrate the feasibility of the method for routine analyses involving environmental samples.
Assuntos
Técnicas Eletroquímicas , Grafite , Ivermectina , Lasers , Ivermectina/análise , Ivermectina/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Grafite/química , Humanos , Limite de Detecção , Antiparasitários/urina , Antiparasitários/análise , Antiparasitários/química , Eletrodos , COVID-19 , SARS-CoV-2RESUMO
Ivermectin is one of the most widely used drugs for parasite control. Previous studies have shown a reduction in the abundance and diversity of "non-target" coprophilous organisms due to the presence of ivermectin (IVM) in bovine faecal matter (FM). Due to its breadth of behavioural habits, Calliphora vicina is a suitable dipteran species to evaluate the effects of IVM in FM. The aim of this work was to evaluate the effect of five concentrations of IVM in FM (3000, 300, 100, 30, and 3 ng/g) on the development of C. vicina. The following endpoints were evaluated: survival (between the first larval stage and emergence of new adults), larval development times to pupation and pupation times to adult, and adult emergence (% sex) and LC50. Sampling was performed from larval hatching at 60 and 120 min and at 3, 4, 5, and 12 h, and every 24 h specimens were weighed until pupae were observed. Data were analysed by ANOVA using a non-parametric Kruskal-Wallis test and as a function of elapsed development time and accumulated degree hours (ADH). Mortality at 3000 and 300 ng/g was 100% and 97%, respectively. There were statistically significant delays in adult emergence time (p = 0.0216) and in the ADH (p = 0.0431) between the control group (C) and 100 ng/g. The LC50 was determined at 5.6 ng/g. These results demonstrate the lethal and sub-lethal effects of IVM on C. vicina, while highlighting the usefulness of this species as a bioindicator for ecotoxicological studies.
Assuntos
Calliphoridae , Fezes , Ivermectina , Larva , Animais , Ivermectina/farmacologia , Calliphoridae/efeitos dos fármacos , Calliphoridae/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Fezes/parasitologia , Bovinos , Análise de Sobrevida , Pupa/efeitos dos fármacos , Pupa/crescimento & desenvolvimento , Feminino , Antiparasitários/farmacologia , Masculino , Dose Letal Mediana , Dípteros/efeitos dos fármacos , Dípteros/crescimento & desenvolvimentoRESUMO
Scavenger receptors participate in a wide range of biological functions after binding to multiple non-self or altered self-ligands. Among them, CD5 and CD6 are lymphocyte scavenger receptors known to interact with different microbial-associated molecular patterns, and the administration of the recombinant soluble ectodomains of human CD5 (rshCD5) and/or CD6 (rshCD6) has shown therapeutic/prophylactic potential in experimental models of fungal, bacterial and echinococcal infections. The latter is a zoonosis caused by the larval stage of the cestode parasite Echinococcus granulosus sensu lato, which in humans can induce secondary cystic echinococcosis (CE) after the spillage of protoscoleces contained within fertile cysts, either spontaneously or during surgical removal of primary hydatid cysts. Herein, we have analysed the mechanisms behind the significant protection observed in the mouse model of secondary CE following prophylactic administration of rshCD5 or rshCD6. Our results show that both molecules exhibit intrinsic antiparasitic activities in vitro, as well as immunomodulatory functions during early secondary CE, mainly through Th1/Th17 cytokine bias and promotion of peritoneal polyreactive antibodies. These data support the relevance of the parasite components bound by rshCD5 and rshCD6, as well as the potential of their prophylactic administration as a useful strategy to reduce secondary CE in patients.
Assuntos
Anti-Infecciosos , Equinococose , Animais , Camundongos , Humanos , Antiparasitários , Zoonoses , Receptores DepuradoresRESUMO
BACKGROUND: Chagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. PURPOSE: To assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. METHODS: Five natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. RESULTS: Through computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. CONCLUSION: The hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.
Assuntos
Alcaloides , Amaryllidaceae , Isoquinolinas , Leishmania infantum , Simulação de Acoplamento Molecular , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Amaryllidaceae/química , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Isoquinolinas/farmacologia , Isoquinolinas/química , Isoquinolinas/isolamento & purificação , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Antiparasitários/farmacologia , Antiparasitários/química , Antiparasitários/isolamento & purificação , Antiprotozoários/farmacologia , Antiprotozoários/química , Antiprotozoários/isolamento & purificaçãoRESUMO
Natural pigments have received special attention from the market and industry as they could overcome the harm to health and the environmental issues caused by synthetic pigments. These pigments are commonly extracted from a wide range of organisms, and when added to products they can alter/add new physical-chemical or biological properties to them. Fungi from extreme environments showed to be a promising source in the search for biomolecules with antimicrobial and antiparasitic potential. This study aimed to isolate fungi from Antarctic soils and screen them for pigment production with antimicrobial and antiparasitic potential, together with other previously isolated strains A total of 52 fungi were isolated from soils in front of the Collins Glacier (Southeast border). Also, 106 filamentous fungi previously isolated from the Collins Glacier (West border) were screened for extracellular pigment production. Five strains were able to produce extracellular pigments and were identified by ITS sequencing as Talaromyces cnidii, Pseudogymnoascus shaanxiensis and Pseudogymnoascus sp. All Pseudogymnoascus spp. (SC04.P3, SC3.P3, SC122.P3 and ACF093) extracts were able to inhibit S. aureus ATCC6538 and two (SC12.P3, SC32.P3) presented activity against Leishmania (L.) infantum, Leishmania amazonensis and Trypanossoma cruzii. Extracts compounds characterization by UPLC-ESI-QToF analysis confirmed the presence of molecules with biological activity such as: Asterric acid, Violaceol, Mollicellin, Psegynamide A, Diorcinol, Thailandolide A. In conclusion, this work showed the potential of Antartic fungal strains from Collins Glacier for bioactive molecules production with activity against Gram positive bacteria and parasitic protozoas.
Assuntos
Antiparasitários , Pigmentos Biológicos , Regiões Antárticas , Pigmentos Biológicos/farmacologia , Pigmentos Biológicos/biossíntese , Antiparasitários/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Fungos/efeitos dos fármacos , Fungos/metabolismo , Fungos/classificação , Microbiologia do Solo , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética , Testes de Sensibilidade Microbiana , Animais , Staphylococcus aureus/efeitos dos fármacosRESUMO
The use of herbal medicine to treat various diseases is becoming increasingly important as an alternative therapy. Numerous plants have been traditionally used for different purposes, including antiparasitic in humans and animals. Diseases caused by gastrointestinal parasites in ruminants, especially by the nematode Haemonchus contortus, cause large economic losses to the producers, whether by complications of the diseases or the cost of treatment. The main way of handling nematodiasis is by administering anthelmintic drugs, but their excessive use has the disadvantage of causing drug resistance; therefore, an alternative is the use of herbal medicine for this purpose. Mesquite (Prosopis spp.) has been used in Mexico to treat gastrointestinal diseases attributed to helminths. The present study aimed to characterize the rheological properties of mesquite flour using the SeDeM Expert System to determine its suitability for tablet production by direct compression. Direct compression technology facilitates the tableting process by reducing manufacturing costs. The results of the present study indicate that mesquite flour can be processed by direct compression. The latter could allow the manufacturing of economic tablets to treat infections by H. contortus in ruminants.