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1.
Rev Bras Parasitol Vet ; 33(3): e004924, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39194144

RESUMEN

In aquaculture worldwide, most of the chemotherapeutic agents used for disease control and treatment are unregulated chemical products derived from agriculture. In this study, we investigated the efficacy of therapeutic baths with albendazole against the monogeneans Anacanthorus spathulatus, Notozothecium janauachensis and Mymarothecium boegeri, which infest the gills of Colossoma macropomum, and the hematological and histopathological effects of this anthelmintic agent on these fish. Albendazole at a concentration of 500 mg/L was used in three baths of 24 hours each, with intervals of 24 hours between these baths. Three replications of this treatment were used, and the control group consisted of water from the cultivation tank. Afterwards, hematological, histopathological and parasitological analyses were conducted. We found that the therapeutic baths with albendazole at 500 mg/L presented high efficacy (94.9%) against monogeneans de C. macropomum and caused few physiological or histopathological alterations. Therefore, baths with albendazole at 500 mg/L, as used in this strategy, can be recommended for controlling and treating infections by monogeneans in C. macropomum.


Asunto(s)
Albendazol , Antihelmínticos , Enfermedades de los Peces , Animales , Enfermedades de los Peces/tratamiento farmacológico , Enfermedades de los Peces/parasitología , Albendazol/uso terapéutico , Albendazol/farmacología , Antihelmínticos/uso terapéutico , Antihelmínticos/farmacología , Characiformes/parasitología , Infecciones por Trematodos/tratamiento farmacológico , Infecciones por Trematodos/veterinaria , Infecciones por Trematodos/parasitología , Trematodos/efectos de los fármacos , Platelmintos/efectos de los fármacos
2.
BMC Vet Res ; 20(1): 334, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39061083

RESUMEN

BACKGROUND: Gills monogenean infestation causes significant mortalities in cultured fishes as a result of respiratory manifestation. Medicinal plants are currently being heavily emphasized in aquaculture due to their great nutritional, therapeutic, antimicrobial activities, and financial value. METHODS: The current study is designed to assess the effect of garlic (Allium sativum) and onion (Allium cepa) extracts as a water treatment on the hematological profile, innate immunity, and immune cytokines expression besides histopathological features of gills of Nile tilapia (Oreochromis niloticus L.) infected with gills monogenetic trematodes (Dactylogyrus sp.). Firstly, the 96-hour lethal concentration 50 (96 h-LC50) of garlic extract (GE) and onion extract (OE) were estimated to be 0.4 g/ L and 3.54 g/ L for GE and OE, respectively. Moreover, the in-vitro anti-parasitic potential for (GE) was found between 0.02 and 0.18 mg/mL and 0.4 to 1.8 mg/mL for OE. For the therapeutic trial, fish (n = 120; body weight: 40-60 g) were randomly distributed into four groups in triplicates (30 fish/group, 10 fish/replicate) for 3 days. Group1 (G1) was not infected or treated and served as control. G2 was infected with Dactylogyrus spp. and not exposed to any treatment. G3, G4 were infected with Dactylogyrus sp. and treated with 1/10 and 1/5 of 96 h LC50 of OE, respectively. G5, G6 were infected with Dactylogyrus sp. and treated with 1/10 and 1/5 of 96 h LC50 of GE, respectively. RESULTS: No apparent signs or behaviors were noted in the control group. Dactylogyrus spp. infected group suffered from clinical signs as Pale color and damaged tissue. Dactylogyrus spp. infection induced lowering of the hematological (HB, MCH, MCHC and WBCs), and immunological variables (lysozyme, nitric oxide, serum Anti- protease activities, and complement 3). the expression of cytokine genes IL-ß and TNF-α were modulated and improved by treatment with A. sativum and A. cepa extracts. The obtained histopathological alterations of the gills of fish infected with (Dactylogyrus spp.) were hyperplasia leading to fusion of the gill filament, lifting of epithelial tissue, aneurism and edema. The results indecated that G4 and G5 is more regenarated epithelium in compare with the control group. CONCLUSION: A. sativum and A. cepa extracts enhance the blood profile and nonspecific immune parameters, and down-regulated the expression level of (IL-1ß and TNF-α).


Asunto(s)
Cíclidos , Citocinas , Enfermedades de los Peces , Ajo , Branquias , Cebollas , Extractos Vegetales , Trematodos , Infecciones por Trematodos , Animales , Branquias/parasitología , Branquias/patología , Branquias/efectos de los fármacos , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/tratamiento farmacológico , Enfermedades de los Peces/inmunología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Cíclidos/inmunología , Cíclidos/parasitología , Ajo/química , Citocinas/genética , Citocinas/metabolismo , Infecciones por Trematodos/veterinaria , Infecciones por Trematodos/tratamiento farmacológico , Infecciones por Trematodos/parasitología , Infecciones por Trematodos/inmunología , Trematodos/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos
3.
Exp Parasitol ; 261: 108748, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38593863

RESUMEN

Monogeneans are parasitic platyhelminths that can harm the health of farmed fish. Few treatments are available against monogeneans, and the incentive to develop new antiparasitic agents is similar or even lower than the incentive for neglected parasitic diseases in humans. Considering that searching for and developing new antimonogenean compounds may require enormous investments of time, money, and animal sacrifice, the use of a computer-guided drug repositioning approach is a reasonable alternative. Under this context, this study aimed to evaluate the effectiveness of plumbagin and bromocriptine against adults and eggs of the monogenean Rhabdosynochus viridisi (Diplectanidae). Plumbagin is a phytochemical compound that has recently emerged as a potent antimonogenean; however, further investigation is required to determine its effects on different monogenean species. Bromocriptine was selected through a computational approach that included molecular docking analyses of 77 receptors of monogeneans (putative drug targets) and 77 ligands (putative inhibitors). In vitro experiments showed that bromocriptine does not exhibit mortality at concentrations of 0.1, 1, and 10 mg/L whereas plumbagin at 2 and 10 mg/L caused 100% monogenean mortality after 3 h and 30 min, respectively. The most effective concentration of plumbagin (10 mg/L) did not completely inhibit egg hatching. These findings underscore plumbagin as a highly effective agent against adult monogeneans and highlight the need for research to evaluate its effect(s) on fish. Although computational drug repositioning is useful for selecting candidates for experimental testing, it does not guarantee success due to the complexity of biological interactions, as observed here with bromocriptine. Therefore, it is crucial to examine the various compounds proposed by this method.


Asunto(s)
Bromocriptina , Reposicionamiento de Medicamentos , Enfermedades de los Peces , Simulación del Acoplamiento Molecular , Naftoquinonas , Bromocriptina/farmacología , Bromocriptina/uso terapéutico , Naftoquinonas/farmacología , Naftoquinonas/química , Animales , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/tratamiento farmacológico , Trematodos/efectos de los fármacos
4.
Acta Parasitol ; 69(2): 1212-1218, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38662072

RESUMEN

PURPOSE: This study investigated the anthelmintic efficacy of therapeutic baths with the essential oil of Piper marginatum Jacq against the monogeneans Anacanthorus spathulatus Kritsky, Thatcher & Kayton, 1979, Notozothecium janauachensis Belmont-Jégu, Domingues & Laterça 2004, Mymarothecium boegeri Cohen & Kohn, 2005 and Linguadactyloides brinkmanni Thatcher & Krytsky, 1983 in Colossoma macropomum Cuvier, 1818, and its hematological and histopathological effects on this fish. METHODS: Short six therapeutic baths with 100 mg/L of the essential oil of P. marginatum and two control groups (water from the cultivation tank and water from the cultivation tank + 70% alcohol) were used for 20 min every two days. RESULTS: The therapeutic baths with 100 mg/L of the essential oil of P. marginatum had efficacy of 42.8% against monogeneans of C. macropomum gills. Toxicity was low for C. macropomum, because there were few physiological and histopathological changes that did not compromise the functioning of the gills of this fish. CONCLUSION: Short therapeutic baths with 100 mg/L of the essential oil of P. marginatum had low efficacy for controlling monogeneans in C. macropomum and thus cannot be recommended.


Asunto(s)
Characiformes , Enfermedades de los Peces , Branquias , Aceites Volátiles , Piper , Infecciones por Trematodos , Animales , Aceites Volátiles/farmacología , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/tratamiento farmacológico , Characiformes/parasitología , Branquias/parasitología , Infecciones por Trematodos/veterinaria , Infecciones por Trematodos/parasitología , Infecciones por Trematodos/tratamiento farmacológico , Piper/química , Antihelmínticos/farmacología , Trematodos/efectos de los fármacos
5.
J Fish Dis ; 44(11): 1819-1829, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34339060

RESUMEN

Parasite infections in fish require constant surveillance and strategies for efficient treatments which guarantee the fish health, their sale value and the non-propagation of pathogens in new environments. Fish treatments based on nanotechnology become of increasing interest since nanoparticles have been shown as efficient materials for optimizing administration of bioactives. In this study a chitosan derivative, alginate and praziquantel conjugated nanobioparticle of effective action for oral treatment of digenetic trematodes in highly infected Corydoras schwartzi was evaluated in terms of histological and hematological safety. The inherent absence of alterations in intestinal tissue and the reversible blood cells counting during a period up to 35 days showed the safety of the drug delivery nanobioparticles, which thus represent a promising strategy for effective applications in pathogens treatments by oral administration.


Asunto(s)
Bagres/parasitología , Enfermedades de los Peces/tratamiento farmacológico , Nanopartículas , Praziquantel/administración & dosificación , Infecciones por Trematodos/veterinaria , Administración Oral , Alginatos , Animales , Quitosano , Portadores de Fármacos , Enfermedades de los Peces/parasitología , Intestinos/efectos de los fármacos , Intestinos/patología , Trematodos/efectos de los fármacos , Infecciones por Trematodos/tratamiento farmacológico
6.
Infect Genet Evol ; 93: 104931, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34023509

RESUMEN

The Excretory/Secretory (ES) proteins of parasites are involved in invasion and colonization of their hosts. In addition, since ES proteins circulate in the extracellular space, they can be more accessible to drugs than other proteins, which makes ES proteins optimal targets for the development of new and better pharmacological strategies. Monogeneans are a group of parasitic Platyhelminthes that includes some pathogenic species problematic for finfish aquaculture. In the present study, 8297 putative ES proteins from four monogenean species which genomic resources are publicly available were identified and functionally annotated by bioinformatic tools. Additionally, for comparative purposes, ES proteins in other parasitic and free-living platyhelminths were identified. Based on data from the monogenean Gyrodactylus salaris, 15 ES proteins are considered potential drug targets. One of them showed homology to 10 cathepsins with known 3D structure. A docking molecular analysis uncovered that the anthelmintic emodepside shows good affinity to these cathepsins suggesting that emodepside can be experimentally tested as a monogenean's cathepsin inhibitor.


Asunto(s)
Antiplatelmínticos/química , Biología Computacional , Desarrollo de Medicamentos , Proteínas del Helminto/genética , Trematodos/efectos de los fármacos , Animales
7.
Parasitol Res ; 120(6): 2135-2148, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33991246

RESUMEN

Habitat loss, climate change, environmental contaminants, and parasites and pathogens are among the main factors thought to act singly or together in causing amphibian declines. We tested for combined effects of neonicotinoid pesticides and parasites (versus parasites-only) on mortality, growth, and white blood cell profiles of a model amphibian: the northern leopard frog (Rana pipiens). We first exposed infectious stages of frog trematodes (cercariae of Echinostoma spp.) to low and high concentrations of thiamethoxam or clothianidin versus water-only controls. There were no differences in survival of trematode cercariae between treatments. For the main experiment, we exposed tadpoles to clean water versus high concentrations of clothianidin or thiamethoxam for 2 weeks and added trematode cercariae to all tanks after 1 week. Exposure of tadpoles and parasites to high concentrations of thiamethoxam or clothianidin did not affect parasite infection success. Tadpole survival was not different between treatments before or after parasite addition and there were no significant differences in tadpole snout-to-vent lengths or developmental stages between treatments. Tadpoles exposed to thiamethoxam + parasites had smaller widths than parasite-only tadpoles, whereas tadpoles exposed to clothianidin + parasites had higher eosinophil to leukocyte ratios compared to parasite-only tadpoles. Tadpoles of both neonicotinoid + parasite treatments had significantly lower monocyte to leukocyte ratios relative to parasite-only tadpoles. High concentrations of neonicotinoid combined with parasites appear to influence tadpole immune function important for further defense against parasites and pathogens. This work highlights the need for more holistic approaches to ecotoxicity studies, using multiple stressors.


Asunto(s)
Células Sanguíneas/efectos de los fármacos , Neonicotinoides/toxicidad , Plaguicidas/toxicidad , Trematodos/patogenicidad , Animales , Recuento de Células Sanguíneas , Células Sanguíneas/patología , Cercarias/efectos de los fármacos , Cercarias/patogenicidad , Echinostoma/patogenicidad , Ecotoxicología , Larva/efectos de los fármacos , Larva/inmunología , Larva/parasitología , Rana pipiens , Trematodos/efectos de los fármacos
8.
Vet Parasitol ; 291: 109385, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33667989

RESUMEN

Paramphistomosis is a pathogenic disease that occurs frequently in tropical and subtropical countries including Thailand. This disease is affected in the parasites causing severe gastrointestinal disorders and death in infected animals. In the present study, we examined the anthelmintic efficacy of albendazole (ABZ) and crude plant extracts from barks of Bombax ceiba L., Diospyros rhodocalyx Kurz. and Vitex glabrata R.Br., and leaves of Terminalia catappa L. and Cassia alata L. against Gastrothylax crumenifer. The hightest anthelmintic activity on the parasites after 24 h incubation was observed in the n-butanol extract of T. catappa leaf. In this study, fractionation bioassay of n-butanol extract of T. catappa leaf was conducted to both separation and discrimination of rutin served as a new efficient compound (LC50 = 28.96; LC90 = 88.75 µg/mL) against G. crumenifer. This compound was confirmed by 1H nuclear magnetic resonance (1H NMR), 13C NMR, infrared (IR) and ultraviolet (UV) spectra as well as mass spectra data. The rutin-treated parasites with all dosages showed swift decrease of the motility and the relative motility (RM) and survival index (SI) were decreased obviously from 3 h until flukes were killed after 12 h of incubation. When observed with light microscopy, the parasites showed the earliest change in a limited region of the tegument. When observed by scanning electron microscopy, the parasites' tegument exhibited similar sequences of surface changes after treatments with rutin and ABZ, but less severity in ABZ treatment. The sequences of changes comprised swelling of folds and ridges, formation of blebbing, rupturing of blebs, erosions, lesions and the tegument demolition. Hence, rutin could be considered as the potential anthelmintic agent for treatment of paramphistomosis.


Asunto(s)
Extractos Vegetales/farmacología , Rutina/farmacología , Terminalia/química , Trematodos/efectos de los fármacos , 1-Butanol/química , Albendazol/farmacología , Animales , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Hojas de la Planta/química , Plantas Medicinales/química , Terminalia/ultraestructura , Infecciones por Trematodos/tratamiento farmacológico
9.
Parasitol Res ; 119(8): 2371-2382, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32607709

RESUMEN

After almost 50 years of praziquantel (PZQ) research, Park and Marchant (Trends Parasitol 36:182-194, 2020) described the Ca++-permeable transient receptor potential (TRP) channel Sm.TRPMPZQ in Schistosoma mansoni as target of PZQ. Here we describe the deadly cascade in schistosomes which is induced by the (R)-PZQ enantiomer that includes contemporaneous stereoselective activation of Sm.TRPMPZQ-mediated Ca++ influx, disturbed Ca++ homeostasis, Ca++-dependent spastic paralysis, and Ca++- and PZQ-dependent disruption of parasitic teguments. Under normal conditions, there is a reversible balance between bilayer, isotropic, and HII phases in biological membranes (Jouhet 2013). In vitro, we could observe an irreversible but not stereoselective transition to the HII phase in liposomes consisting of phosphatidylethanolamine (PE) and phosphatidylserine (PS), two naturally occurring phospholipids in schistosomes, by the concerted action of Ca++ and PZQ (Harder 2013). HII structures are a prerequisite for induction of fusion processes (Jouhet 2013), which, indeed, become visible as blebs, vacuolation processes, and large balloon-like surface exudates in a large variety of PZQ-sensitive parasitic flukes and cestodes after PZQ treatment. These tegument damages are irreversible. As homologs of Sm.TRPMPZQ are also present in the other trematodes S. japonicum, S. haematobium, or Clonorchis sinensis and cestodes Taenia solium, Echinococcus multilocularis, or Hymenolepis microstoma (Park and Marchant, Trends Parasitol 36:182-194, 2020), it is suggested that a similar deadly cascade will be operating generally in PZQ-sensitive parasites.


Asunto(s)
Cestodos/efectos de los fármacos , Praziquantel/farmacología , Schistosoma mansoni/efectos de los fármacos , Trematodos/efectos de los fármacos , Animales , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitología , Canales Catiónicos TRPM/efectos de los fármacos
10.
J Aquat Anim Health ; 32(3): 127-132, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32506710

RESUMEN

Monogeneans are parasitic flatworms that may be a threat for finfish aquaculture. In this study, the anthelmintic activity of two terpenes, geraniol and ß-citronellol, was tested in vitro against ancyrocephalin and diplectanid monogeneans. Experiments were performed in both water and a culture medium. We observed that monogeneans in culture medium may be more tolerant to treatments compared with bioassays performed only in water. Concentrations of 300 mg/L of both compounds were required to kill 100% of monogeneans at 1 h postexposure. The toxicity of ß-citronellol to fish was not evaluated. However, geraniol at 300 mg/L and 150 mg/L killed juvenile Nile Tilapia Oreochromis niloticus and White Snook Centropomus viridis, respectively, after a few minutes. Therefore, the present work suggests that other alternatives should be studied for use against monogeneans in aquaculture.


Asunto(s)
Monoterpenos Acíclicos , Cíclidos , Perciformes , Trematodos/efectos de los fármacos , Monoterpenos Acíclicos/efectos adversos , Monoterpenos Acíclicos/farmacología , Animales , Antihelmínticos/efectos adversos , Antihelmínticos/farmacología , Especificidad de la Especie
11.
Acta Parasitol ; 65(3): 804-809, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32394290

RESUMEN

PURPOSE: The aim of this study was to evaluate the in vitro and in vivo efficacy of propolis against Ligictaluridus floridanus on Ictalurus punctatus gills. METHODS: This study used an ethanol extract of propolis at a concentration of 300 mg mL-1, with a total polyphenol concentration of 2.77 mg mL-1 as determined by chromatography. In vitro trial used propolis concentrations at 5, 30 as well as 60 mg L-1 and a 70% ethanol control group to treat naturally infected catfish. The in vivo experiment was 16 weeks in duration, consisting of seventy-two fish infected by cohabitation and subjected to one-hour baths every 72 h during the trial. RESULTS: In vitro studies showed that parasites exposed to 60 mg L-1 of propolis displayed a significant reduction (p < 0.05) in their survival time. In vivo studies confirmed the reduction of intensity and abundance of Ligictaluridus floridanus on the gills of channel catfish. CONCLUSION: This study has provided the first challenge of propolis against L. floridanus on I. punctatus gills and shows that propolis has an anthelmintic effect.


Asunto(s)
Bagres/parasitología , Enfermedades de los Peces/parasitología , Própolis/farmacología , Trematodos/efectos de los fármacos , Infecciones por Trematodos/veterinaria , Animales , Antihelmínticos/farmacología , Branquias/parasitología , Trematodos/aislamiento & purificación
12.
J Helminthol ; 94: e150, 2020 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-32381146

RESUMEN

Many temperate freshwater habitats are at risk for contamination by run-off associated with the application of road de-icing salts. Elevated salinity can have various detrimental effects on freshwater organisms, including greater susceptibility to infection by parasites and pathogens. However, to better understand the net effects of road salt exposure on host-parasite dynamics, it is necessary to consider the impacts on free-living parasite infectious stages, such as the motile aquatic cercariae of trematodes. Here, we examined the longevity and activity of cercariae from four different freshwater trematodes (Ribeiroia ondatrae, Echinostoma sp., Cephalogonimus sp. and an unidentified strigeid-type) that were exposed to road salt at five different environmentally relevant concentrations (160, 360, 560, 760 and 960 mg/ml of sodium chloride). Exposure to road salt had minimal detrimental effects, with cercariae activity and survival often greatest at intermediate concentrations. Only the cercariae of Cephalogonimus sp. showed reduced longevity at the highest salt concentration, with those of both R. ondatrae and the unidentified strigeid-type exhibiting diminished activity, indicating interspecific variation in response. Importantly, cercariae seem to be relatively unaffected by salt concentrations known to increase infection susceptibility in some of their hosts. More studies will be needed to examine this potential dichotomy in road salt effects between hosts and trematodes, including influences on parasite infectivity.


Asunto(s)
Cloruro de Sodio/farmacología , Trematodos/efectos de los fármacos , Contaminantes Químicos del Agua/farmacología , Animales , Cercarias/efectos de los fármacos , Cercarias/fisiología , Agua Dulce , Salinidad , Trematodos/fisiología
13.
J Fish Dis ; 43(6): 687-695, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32315094

RESUMEN

This study compared the in vitro anthelmintic activity of Copaifera reticulata oleoresin (200, 400, 600, 800 and 1,000 mg/L) and of nanoemulsions prepared with this oleoresin (50, 100, 150, 200 and 250 mg/L) against monogeneans on the gills of Colossoma macropomum. The major compounds present in the oleoresin of C. reticulata were γ-macrocarpene (14.2%), α-bergamotene (13.6%), ß-selinene (13.4%) and ß-caryophyllene (11.7%). All concentrations of the nanoemulsion and the oleoresin without nanoformulation showed anthelmintic efficacy against monogeneans, and higher concentrations led to more rapid parasite mortality. Structural damages to the tegument of the parasites exposed to C. reticulata oleoresin were observed with scanning electron microscopy. At two hours of exposure, fish showed 100% tolerance to all nanoemulsion concentrations used in the in vitro assays, whereas 100% mortality was shown in the fish exposed to the oleoresin without nanoformulation after one hour. The results of this study suggest that nanoemulsions with oleoresin of C. reticulata have advantages in the control and treatment of monogenean infections in C. macropomum when compared to the oleoresin without nanoformulation. In addition, since nanoemulsions with the C. reticulata oleoresin are safe to control monogeneans, the efficacy of these nanoformulations may be assayed in therapeutic baths to treat C. macropomum infected by monogeneans.


Asunto(s)
Antiplatelmínticos/farmacología , Fabaceae/química , Enfermedades de los Peces/tratamiento farmacológico , Extractos Vegetales/farmacología , Trematodos/efectos de los fármacos , Infecciones por Trematodos/veterinaria , Animales , Compuestos Bicíclicos con Puentes/farmacología , Relación Dosis-Respuesta a Droga , Emulsiones/química , Enfermedades de los Peces/parasitología , Nanoestructuras/química , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos de Eudesmano/farmacología , Tetrahidronaftalenos/farmacología , Infecciones por Trematodos/tratamiento farmacológico , Infecciones por Trematodos/parasitología
14.
Sci Rep ; 10(1): 2587, 2020 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-32054976

RESUMEN

Trematode infections such as schistosomiasis and fascioliasis cause significant morbidity in an estimated 250 million people worldwide and the associated agricultural losses are estimated at more than US$ 6 billion per year. Current chemotherapy is limited. Triosephosphate isomerase (TIM), an enzyme of the glycolytic pathway, has emerged as a useful drug target in many parasites, including Fasciola hepatica TIM (FhTIM). We identified 21 novel compounds that selectively inhibit this enzyme. Using microscale thermophoresis we explored the interaction between target and compounds and identified a potent interaction between the sulfonyl-1,2,4-thiadiazole (compound 187) and FhTIM, which showed an IC50 of 5 µM and a Kd of 66 nM. In only 4 hours, this compound killed the juvenile form of F. hepatica with an IC50 of 3 µM, better than the reference drug triclabendazole (TCZ). Interestingly, we discovered in vitro inhibition of FhTIM by TCZ, with an IC50 of 7 µM suggesting a previously uncharacterized role of FhTIM in the mechanism of action of this drug. Compound 187 was also active against various developmental stages of Schistosoma mansoni. The low toxicity in vitro in different cell types and lack of acute toxicity in mice was demonstrated for this compound, as was demonstrated the efficacy of 187 in vivo in F. hepatica infected mice. Finally, we obtained the first crystal structure of FhTIM at 1.9 Å resolution which allows us using docking to suggest a mechanism of interaction between compound 187 and TIM. In conclusion, we describe a promising drug candidate to control neglected trematode infections in human and animal health.


Asunto(s)
Antihelmínticos/química , Antihelmínticos/farmacología , Trematodos/efectos de los fármacos , Trematodos/enzimología , Infecciones por Trematodos/tratamiento farmacológico , Triosa-Fosfato Isomerasa/antagonistas & inhibidores , Animales , Antihelmínticos/uso terapéutico , Cristalografía por Rayos X , Descubrimiento de Drogas , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Fasciola hepatica/efectos de los fármacos , Fasciola hepatica/enzimología , Fascioliasis/tratamiento farmacológico , Fascioliasis/parasitología , Femenino , Masculino , Mesocricetus , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/enzimología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitología , Infecciones por Trematodos/parasitología , Triosa-Fosfato Isomerasa/metabolismo
15.
Vet Ital ; 56(4): 271-287, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33635616

RESUMEN

Four ferns Blechnum orientale Linn. (BO), Dicranopteris linearis (Burm.f ) Underw. (DL), Marattia fraxinea Sm. (MF), and Microlepia speluncae (L.) Moore (MS) were extracted in varied combination of organic solvents followed by the preparation of eluates and isolation of secondary metabolites using chromatography on a glass column with silica gel as the fixed phase. The chemical components were identified using HPTLC and GC-MS analysis. The in vitro anti-trematodal activities of these eluates and compounds were evaluated against the sheep trematode worm Gastrothylax crumenifer (Plagiorrchiida: Gastrothylacidae) at increasing concentrations (1 to 5 mg/mL), to find the relative motility (RM) values for 0 to 60 min of incubation as reflection of paralysis and death of the worms. Hedon-Fleig salt solution was used as negative control and Oxyclozanide® 1% as standard control. In vitro incubation study showed DL and MS extracts had strong trematodicidal activity. BO extract (5 mg/mL) produced moderate trematodicidal activity and MF (5 mg/mL) showed the least trematodicidal activity. Phytochemicals analysis revealed that the ferns are a potential source of trematodicidal compounds such as phytol isomers fern-8-ene and fern-9(11)-ene (terpenoid derivative), quercetin 7,3 ́,4 ́-trimethoxy (flavonoid derivative), etc., which offer scope for a more elaborate study for exploitation of ferns for human welfare.


Asunto(s)
Antiplatelmínticos/farmacología , Helechos , Extractos Vegetales/farmacología , Enfermedades de las Ovejas/tratamiento farmacológico , Trematodos/efectos de los fármacos , Infecciones por Trematodos/veterinaria , Animales , Antiplatelmínticos/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Ovinos , Enfermedades de las Ovejas/parasitología , Infecciones por Trematodos/tratamiento farmacológico
16.
Rev. bras. parasitol. vet ; 28(4): 708-712, Oct.-Dec. 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1057979

RESUMEN

Abstract This study investigated the effects of diets supplemented with levamisole on monogeneans on the gills of Colossoma macropomum. Fish were fed with diets containing levamisole at concentrations of 0, 300, 600, 900 and 1200 mg kg-1 for 24, 96 and 240 h and the infection by Anacanthorus spatulatus, Notozothecium janauachensis and Mymarothecium boegeri were evaluated. None of the levamisole concentrations caused either mortality or behavioral alterations in fishes during 240 h of feeding. After 24 h of feeding with 1200 mg kg-1 of levamisole, the abundance of N. janauachensis decreased in comparison with treatments of 0, 300, 600 and 900 mg kg-1, as did the abundance of M. boegeri after 240 h of feeding with 1200 mg kg-1 of levamisole. The efficacy of 900 mg kg-1 of levamisole was only 55.7% after 96 h of feeding, but it was 84.6% after 240 h of feeding with 1200 mg kg-1. Our results show that 1200 mg kg-1 of levamisole for 10 days has good anthelmintic efficacy against monogeneans of C. macropomum. Since monogeneans elicit some of the worst problems in C. macropomum, this study has provided evidence of an effective control method that may be used in fish farms.


Resumo Este estudo investigou os efeitos de dietas suplementadas com levamisol na infecção por monogeneas nas brânquias de Colossoma macropomum. Os peixes foram alimentados com dietas contendo 0, 300, 600, 900 e 1200 mg kg-1 de levamisol por 24, 96 e 240 h e os níveis de infecção por Anacanthorus spatulatus, Notozothecium janauachensis e Mymarothecium boegeri, foram avaliados. Nenhuma das concentrações de levamisol causou mortalidade ou alterações comportamentais nos peixes durante 240 h de alimentação. Após 24 h de alimentação com 1.200 mg kg-1 de levamisol, a abundância de N. janauachensis diminuiu quando comparada aos tratamentos com 0, 300, 600 e 900 mg kg-1, bem como a abundância de M. boegeri após 240 h de alimentação com 1200 mg kg-1 de levamisol. A eficácia de 900 mg kg-1 de levamisol foi somente de 55,7% após 96 h de alimentação, mas foi de 84,6% após 240 h de alimentação com 1200 mg kg-1. Os resultados mostram que 1200 mg kg-1 de levamisol durante 10 dias, tem uma boa eficácia antihelmíntica contra monogeneas de C. macropomum. Como monogeneas provocam alguns dos piores problemas em C. macropomum, este estudo forneceu evidências de um método de controle eficaz que pode ser usado em pisciculturas.


Asunto(s)
Animales , Trematodos/efectos de los fármacos , Levamisol/administración & dosificación , Dieta , Enfermedades de los Peces/prevención & control , Peces/parasitología , Alimentación Animal , Antinematodos/administración & dosificación , Enfermedades de los Peces/parasitología
17.
Rev Bras Parasitol Vet ; 28(4): 708-712, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31721932

RESUMEN

This study investigated the effects of diets supplemented with levamisole on monogeneans on the gills of Colossoma macropomum. Fish were fed with diets containing levamisole at concentrations of 0, 300, 600, 900 and 1200 mg kg-1 for 24, 96 and 240 h and the infection by Anacanthorus spatulatus, Notozothecium janauachensis and Mymarothecium boegeri were evaluated. None of the levamisole concentrations caused either mortality or behavioral alterations in fishes during 240 h of feeding. After 24 h of feeding with 1200 mg kg-1 of levamisole, the abundance of N. janauachensis decreased in comparison with treatments of 0, 300, 600 and 900 mg kg-1, as did the abundance of M. boegeri after 240 h of feeding with 1200 mg kg-1 of levamisole. The efficacy of 900 mg kg-1 of levamisole was only 55.7% after 96 h of feeding, but it was 84.6% after 240 h of feeding with 1200 mg kg-1. Our results show that 1200 mg kg-1 of levamisole for 10 days has good anthelmintic efficacy against monogeneans of C. macropomum. Since monogeneans elicit some of the worst problems in C. macropomum, this study has provided evidence of an effective control method that may be used in fish farms.


Asunto(s)
Alimentación Animal , Antinematodos/administración & dosificación , Dieta , Enfermedades de los Peces/prevención & control , Peces/parasitología , Levamisol/administración & dosificación , Trematodos/efectos de los fármacos , Animales , Enfermedades de los Peces/parasitología
18.
Int J Parasitol ; 49(13-14): 1015-1021, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31655036

RESUMEN

Human activities have caused an increase in atmospheric CO2 over the last 250 years, leading to unprecedented rates of change in seawater pH and temperature. These global scale processes are now commonly referred to as ocean acidification and warming, and have the potential to substantially alter the physiological performance of many marine organisms. It is vital that the effects of ocean acidification and warming on marine organisms are explored so that we can predict how marine communities may change in future. In particular, the effect of ocean acidification and warming on host-parasite dynamics is poorly understood, despite the ecological importance of these relationships. Here, we explore the response of one himasthlid trematode, Himasthla sp., an abundant and broadly distributed species of marine parasite, to combinations of elevated temperature and pCO2 that represent physiological extremes, pre-industrial conditions, and end of century predictions. Specifically, we quantified the life span of the free-living cercarial stage under elevated temperature and pCO2, focussing our research on functional life span (the time cercariae spend actively swimming) and absolute life span (the period before death). We found that the effects of temperature and pCO2 were complex and interactive. Overall, increased temperature negatively affected functional and absolute life span, e.g. across all pCO2 treatments the average time to 50% cessation of active swimming was approximately 8 h at 5 °C, 6 h at 15 °C, 4 h at 25 °C, and 2 h at 40 °C. The effect of pCO2, which significantly affected absolute life span, was highly variable across temperature treatments. These results strongly suggest that ocean acidification and warming may alter the transmission success of trematode cercariae, and potentially reduce the input of cercariae to marine zooplankton. Either outcome could substantially alter the community structure of coastal marine systems.


Asunto(s)
Concentración de Iones de Hidrógeno , Longevidad/efectos de los fármacos , Longevidad/efectos de la radiación , Agua de Mar/química , Temperatura , Trematodos/efectos de los fármacos , Trematodos/efectos de la radiación , Animales , Organismos Acuáticos/efectos de los fármacos , Organismos Acuáticos/efectos de la radiación , Calentamiento Global
19.
J Parasitol ; 105(4): 598-605, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31418652

RESUMEN

Eutrophication of aquatic habitats has become a global problem, with implications for host-parasite dynamics. Blooms of certain cyanobacteria are associated with cyanotoxins, particularly microcystins such as microcystin-LR (MC-LR). These potent toxins have been shown to adversely affect freshwater fauna and can increase host susceptibility to parasite infection. However, to understand how cyanotoxins influence infection outcomes in nature, it is necessary to investigate whether free-living parasite infectious stages, such as that of trematode cercariae, are also affected given their demonstrated sensitivity to various contaminants. Here we examined the effects of environmentally relevant levels of MC-LR representing relatively high (82 µg/L) and low (11 µg/L) concentrations on the activity and survival of four different types of cercariae ( Echinostoma sp., Cephalogonimus sp., Alaria sp., and an unidentified strigeid type) over 24 hr. Exposure to MC-LR did not affect the activity of any cercarial type, nor was survival reduced. In fact, the strigeid-type cercariae had significantly increased longevity if exposed to either MC-LR solution, with the greatest longevity in the highest concentration. Our results indicate that MC-LR may have opposing effects on aquatic parasites and their hosts, potentially increasing host susceptibility but having a neutral or positive effect on motile infectious stages such as cercariae. Cyanobacterial blooms could thus enhance trematode transmission; however, the effects of other cyanotoxins must be studied, as well as a broader range of host and parasite species.


Asunto(s)
Toxinas Bacterianas/toxicidad , Toxinas Marinas/toxicidad , Microcistinas/toxicidad , Trematodos/efectos de los fármacos , Animales , Cercarias/efectos de los fármacos , Toxinas de Cianobacterias , Relación Dosis-Respuesta a Droga , Echinostoma/efectos de los fármacos , Eutrofización , Modelos Lineales , Estanques , Caracoles/parasitología
20.
Acta Parasitol ; 64(4): 927-931, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31286361

RESUMEN

INTRODUCTION: Herbal therapy is a potentially beneficial alternative for fish aquaculture, since it may be cheaper and more effective than chemotherapy. The aim of this study was to investigate the in vitro efficacy of Ficus insipida latex on monogeneans of Colossoma macropomum gills. MATERIALS AND METHODS: To evaluate the anthelmintic activity, four concentrations of F. insipida latex (250, 500, 750 and 1000 µL/L) and exposure time to cause immobilization on monogeneans were used. In addition, two control groups, being one with water from the breeding tank and the other with breeding water from the tank + 70% ethyl alcohol were used. RESULTS: At the concentration of 250 µL/L of F. insipida latex, the immobilization of the monogeneans occurred after 4 h of exposure, while at the concentration of 500 µL/L, it occurred after 2 h. At the concentrations of 750 and 1000 µL/L of F. insipida latex, the immobilization of the monogeneans occurred after 1 h and 30 min, respectively. After exposure to 250 µL/L of F. insipida latex, 100% of immobilization of monogeneans was observed within 4 h, to 500 and 750 µL/L, 100% immobilization occurred within 4 h and to 1000 µL/L, 100% mortality occurred after 2 h. CONCLUSIONS: Thus, we recommended the use of 1000 µL/L of F. insipida latex for therapeutic baths in of C. macropomum against monogeneans, after previous test of toxicity.


Asunto(s)
Antihelmínticos/farmacología , Ficus/química , Látex/farmacología , Plantas Medicinales/química , Trematodos/efectos de los fármacos , Animales , Acuicultura , Characiformes/parasitología , Enfermedades de los Peces/tratamiento farmacológico , Enfermedades de los Peces/parasitología , Branquias/parasitología , Látex/química , Pruebas de Sensibilidad Parasitaria , América del Sur
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