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1.
Int J Mol Sci ; 25(19)2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39408999

RESUMO

Organic compounds with antibacterial and antiparasitic properties are gaining significance for biomedical applications. This study focuses on the solvent-free synthesis (green synthesis) of 1,4-naphthoquinone or 2,3-dichloro-1,4-naphthoquinone with different phenylamines using silica gel as an acid solid support. The study also includes in silico PASS predictions and the discovery of antibacterial and antiparasitic properties of phenylaminonaphthoquinone derivatives 1-12, which can be further applied in drug discovery and development. These activities were discussed in terms of molecular descriptors such as hydrophobicity, molar refractivity, and half-wave potentials. The in vitro antimicrobial potential of the synthesized compounds 1-12 was evaluated against a panel of six bacterial strains (three Gram-positive: Staphylococcus aureus, Proteus mirabilis, and Enterococcus faecalis; and three Gram-negative bacteria: Escherichia coli, Salmonella typhimurium, and Klebsiella pneumoniae). Six compounds (1, 3, 5, 7, 10, and 11) showed better activity toward S. aureus with MIC values between 3.2 and 5.7 µg/mL compared to cefazolin (MIC = 4.2 µg/mL) and cefotaxime (MIC = 8.9 µg/mL), two cephalosporin antibiotics. Regarding in vitro antiplasmodial activity, compounds 1 and 3 were the most active against the Plasmodium falciparum strain 3D7 (chloroquine-sensitive), displaying IC50 values of 0.16 and 0.0049 µg/mL, respectively, compared to chloroquine (0.33 µg/mL). In strain FCR-3 (chloroquine-resistant), most of the compounds showed good activity, with compounds 3 (0.12 µg/mL) and 11 (0.55 µg/mL) being particularly noteworthy. Additionally, docking studies were used to better rationalize the action and prediction of the binding modes of these compounds. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Naftoquinonas , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Naftoquinonas/farmacologia , Naftoquinonas/química , Naftoquinonas/síntese química , Antiparasitários/farmacologia , Antiparasitários/síntese química , Antiparasitários/química , Química Verde/métodos , Bactérias Gram-Negativas/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos
2.
Rev Bras Parasitol Vet ; 33(3): e003324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39140496

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/parasitologia
3.
J Fish Dis ; 47(11): e14010, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39163500

RESUMO

This study aimed to perform in vitro antiparasitic and antimicrobial tests with the essential oil (EO) of Schinus terebinthifolius against of fish and shrimp. The chemical composition of the EO of S. terebinthifolius was determined by gas chromatography. For the antiparasitic test, the protozoan Epistylis sp. obtained from parasitized Oreochromis niloticus was used, and exposed to different concentrations of EO (2%, 1%, 0.5%, 0.25%), and control with 1% grain alcohol. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) test with EO of S. terebinthifolius evaluated the antimicrobial potential, with serial dilutions starting at 2% and control with 1% grain alcohol, using the strains of Aeromonas hydrophila (2.2 × 108 CFU mL-1), Edwardsiella tarda, Vibrio parahaemolyticus, V. harveyi, and V. alginolyticus (2.0 × 108 CFU mL-1). Chemical analysis revealed that the major EO compounds of S. terebinthifolius were δ-3-Carene (56.00%) and α-Pinene (16.89%). In the antiparasitic test, the concentration of 2% EO showed 100% efficacy against Epistylis sp. within 5 min. In the antimicrobial tests, the concentration of 2% EO was effective against all bacteria tested. The EO of S. terebinthifolius demonstrated antiparasitic and antimicrobial activity at a concentration of 2%, standing out as an alternative to conventional antibiotics.


Assuntos
Anacardiaceae , Doenças dos Peixes , Testes de Sensibilidade Microbiana , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia , Doenças dos Peixes/parasitologia , Anacardiaceae/química , Antiparasitários/farmacologia , Ciclídeos , Antibacterianos/farmacologia , Penaeidae/microbiologia , Schinus
4.
Environ Sci Pollut Res Int ; 31(32): 45425-45440, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965109

RESUMO

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/metabolismo
5.
Theriogenology ; 227: 92-101, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39047407

RESUMO

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 , Feminino
6.
Anal Methods ; 16(25): 4136-4142, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38860551

RESUMO

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-2
7.
Artigo em Inglês | MEDLINE | ID: mdl-38885750

RESUMO

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 fármacos
8.
Parasitol Res ; 123(5): 211, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748261

RESUMO

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 & desenvolvimento
9.
Parasite Immunol ; 46(4): e13034, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38625016

RESUMO

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 Depuradores
10.
Braz J Microbiol ; 55(2): 1251-1263, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492163

RESUMO

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 fármacos
11.
Phytomedicine ; 128: 155414, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503155

RESUMO

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 & purificação
12.
PLoS Negl Trop Dis ; 18(2): e0011961, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38408095

RESUMO

BACKGROUND: Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases. METHODOLOGY: This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation. RESULTS: We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed ~13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/µL, higher viral load, and absence of antiretroviral therapy. CONCLUSION: We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.


Assuntos
Doença de Chagas , Coinfecção , Infecções por HIV , Nitroimidazóis , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/genética , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Estudos Longitudinais , Estudos Transversais , Estudos Prospectivos , Doença de Chagas/complicações , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Nitroimidazóis/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Reação em Cadeia da Polimerase , Antiparasitários/uso terapêutico , Coinfecção/parasitologia
13.
Trop Anim Health Prod ; 56(2): 81, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368294

RESUMO

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.


Assuntos
Anti-Helmínticos , Haemonchus , Prosopis , Doenças dos Ovinos , Humanos , Ovinos , Animais , Antiparasitários , Farinha , Extratos Vegetais , Comprimidos , Ruminantes , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologia
14.
Acta Trop ; 252: 107141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342286

RESUMO

The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals.


Assuntos
Anti-Helmínticos , Hepatopatias , Esquistossomose mansoni , Esquistossomose , Animais , Camundongos , Schistosoma mansoni , Antiparasitários/uso terapêutico , Praziquantel/farmacologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Fígado/parasitologia , Esquistossomose/tratamento farmacológico , Inflamação/tratamento farmacológico , Fibrose , Dieta , Sacarose/farmacologia , Sacarose/uso terapêutico , Anti-Helmínticos/uso terapêutico
15.
Parasitol Res ; 123(2): 143, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407619

RESUMO

The objective of the study was to evaluate the in vitro and in vivo schistosomicidal activity of sanguinarine (SA) on Schistosoma mansoni and its in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The activity of SA in vitro, at the concentrations of 1.0-25 µM, was analyzed through the parameters of motility, mortality, and cell viability of the worms at intervals of 3-24 h. Mice were infected with cercariae and treated by gavage with SA (5 mg/kg/day, in a single dose or two doses of 2.5 mg/kg every 12 h for 5 consecutive days) on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms), and 45th (adult worms) days after infection. In vitro and in vivo praziquantel was the control. In vitro, SA showed schistosomicidal activity against schistosomula, young worms, and couples; with total mortality and reduced cell viability at low concentrations and incubation time. In a single dose of 5 mg/kg/day, SA reduces the total worm load by 47.6%, 54%, 55.2%, and 27.1%, and female worms at 52.0%, 39.1%, 52.7%, and 20.2%, respectively, results which are similar to the 2.5 mg/kg/day dose. SA reduced the load of eggs in the liver, and in histopathological and histomorphometric analyses, there was a reduction in the number and volume of hepatic granulomas, which exhibited less inflammatory infiltrate. SA has promising in vitro and in vivo schistosomicidal activity against different developmental stages of S. mansoni, in addition to reducing granulomatous liver lesions. Furthermore, in silico, SA showed good predictive pharmacokinetic ADMET profiles.


Assuntos
Alcaloides , Anti-Infecciosos , Isoquinolinas , Esquistossomicidas , Feminino , Animais , Camundongos , Antiparasitários , Schistosoma mansoni , Benzofenantridinas/farmacologia , Alcaloides/farmacologia
16.
PLoS Negl Trop Dis ; 18(2): e0011956, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38359089

RESUMO

BACKGROUND: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and leads to ~10,000 deaths each year. Nifurtimox and benznidazole are the only two drugs available but have significant adverse effects and limited efficacy. New chemotherapeutic agents are urgently required. Here we identified inhibitors of the acidic M17 leucyl-aminopeptidase from T. cruzi (LAPTc) that show promise as novel starting points for Chagas disease drug discovery. METHODOLOGY/PRINCIPAL FINDINGS: A RapidFire-MS screen with a protease-focused compound library identified novel LAPTc inhibitors. Twenty-eight hits were progressed to the dose-response studies, from which 12 molecules inhibited LAPTc with IC50 < 34 µM. Of these, compound 4 was the most potent hit and mode of inhibition studies indicate that compound 4 is a competitive LAPTc inhibitor, with Ki 0.27 µM. Compound 4 is selective with respect to human LAP3, showing a selectivity index of >500. Compound 4 exhibited sub-micromolar activity against intracellular T. cruzi amastigotes, and while the selectivity-window against the host cells was narrow, no toxicity was observed for un-infected HepG2 cells. In silico modelling of the LAPTc-compound 4 interaction is consistent with the competitive mode of inhibition. Molecular dynamics simulations reproduce the experimental binding strength (-8.95 kcal/mol), and indicate a binding mode based mainly on hydrophobic interactions with active site residues without metal cation coordination. CONCLUSIONS/SIGNIFICANCE: Our data indicates that these new LAPTc inhibitors should be considered for further development as antiparasitic agents for the treatment of Chagas disease.


Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Leucil Aminopeptidase/química , Leucil Aminopeptidase/farmacologia , Leucil Aminopeptidase/uso terapêutico , Doença de Chagas/tratamento farmacológico , Descoberta de Drogas , Antiparasitários/uso terapêutico , Tripanossomicidas/uso terapêutico
17.
Artigo em Inglês | MEDLINE | ID: mdl-38324876

RESUMO

Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.


Assuntos
Doença de Chagas , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Nitroimidazóis , Trypanosoma cruzi , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/complicações , Antiparasitários/uso terapêutico , Parasitemia/tratamento farmacológico , Parasitemia/epidemiologia , Parasitemia/parasitologia , Estudos Prospectivos , Transplante Autólogo , Doença de Chagas/tratamento farmacológico , Doença de Chagas/epidemiologia , Nitroimidazóis/uso terapêutico
18.
Arch Microbiol ; 206(2): 78, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277061

RESUMO

Varicellovirus bovinealpha 1 (formerly bovine alphaherpesvirus type 1, BoAHV-1) is associated with several syndromes in cattle, including respiratory disease and is one of the main agents involved in the bovine respiratory disease complex (BRDC). Its infectious cycle is characterized by latent infections with sporadic virus reactivation and transmission. Although the acute disease can be prevented by the use of vaccines, specific therapeutic measures are not available. Ivermectin (IVM) is a semi-synthetic avermectin with a broad-spectrum antiparasitic activity, which has previously shown to have potential as an antiviral drug. In this study, IVM antiviral activity against BoAHV-1 was characterized in two cell lines (MDBK [Madin Darby bovine kidney] and BT [bovine turbinate]), including the measurement of intracellular drug accumulation within virus-infected cells. IVM antiviral activity was assessed at three different drug concentrations (1.25, 2.5 and 5 µM) after incubation for 24, 48 and 72 h. Slight cytotoxicity was only observed with 5 µM IVM. Even the lowest IVM dose was able to induce a significant reduction in virus titers in both cell lines. These findings indicate that the antiviral effects of IVM were evident in our experimental model within the range of concentrations achievable through therapeutic in vivo administration. Consequently, additional in vivo trials are necessary to validate the potential utility of these results in effectively managing BoAHV-1 in infected cattle.


Assuntos
Ivermectina , Varicellovirus , Animais , Bovinos , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Antivirais/farmacologia
19.
Curr Top Med Chem ; 24(2): 89-108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37842892

RESUMO

Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by Leishmania, Trypanosoma, and Plasmodium parasites.


Assuntos
Antiprotozoários , Produtos Biológicos , Doença de Chagas , Leishmaniose , Malária , Tripanossomíase Africana , Animais , Humanos , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Antiparasitários/química , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Antiprotozoários/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Tripanossomíase Africana/tratamento farmacológico , Leishmaniose/tratamento farmacológico , Doença de Chagas/tratamento farmacológico , Malária/tratamento farmacológico
20.
Probiotics Antimicrob Proteins ; 16(1): 259-274, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36637793

RESUMO

The research aims to give new insights on the effect of administering selected bacterial strains, isolated from honey bee gut, and/or a commercial plant extract blend (HiveAlive®) on Nosema ceranae. Analyses were first performed under laboratory conditions such as different infective doses of N. ceranae, the effect of single strains and their mixture and the influence of pollen administration. Daily survival and feed consumption rate were recorded and pathogen development was analysed using qPCR and microscope counts. Biomarkers of immunity and physiological status were also evaluated for the different treatments tested using one bacterial strain, a mixture of all the bacteria and/or a plant extract blend as treatments. The results showed an increase of abaecin transcript levels in the midgut of the honey bees treated with the bacterial mixture and an increased expression of the protein vitellogenin in the haemolymph of honey bees treated with two separate bacterial strains (Bifidobacterium coryneforme and Apilactobacillus kunkeei). A significant effectiveness in reducing N. ceranae was shown by the bacterial mixture and the plant extract blend regardless of the composition of the diet. This bioactivity was seasonally linked. Quantitative PCR and microscope counts showed the reduction of N. ceranae under different experimental conditions. The antiparasitic efficacy of the treatments at field conditions was studied using a semi-field approach which was adapted from research on insecticides for the first time, to analyse antiparasitic activity against N. ceranae. The approach proved to be reliable and effective in validating data obtained in the laboratory. Both the mixture of beneficial bacteria and its association with Hive Alive® are effective in controlling the natural infection of N. ceranae in honey bee colonies.


Assuntos
Nosema , Extratos Vegetais , Abelhas , Animais , Vitelogeninas , Antiparasitários
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