Experimental parasitology最新文献

{"title":"Anthelmintic efficacy of an organic fraction from Guazuma ulmifolia leaves and evaluation of reactive oxidative stress on Haemonchus contortus","authors":"Guillermo Reséndiz-González ,&nbsp;Agustín Olmedo-Juárez ,&nbsp;Roberto González-Garduño ,&nbsp;Jorge Alberto Cortes-Morales ,&nbsp;Manasés González-Cortazar ,&nbsp;Ana Elvia Sánchez-Mendoza ,&nbsp;María Eugenia López-Arellano ,&nbsp;Crisóforo Mercado-Márquez ,&nbsp;Alejandro Lara-Bueno ,&nbsp;Rosa Isabel Higuera-Piedrahita","doi":"10.1016/j.exppara.2024.108768","DOIUrl":"10.1016/j.exppara.2024.108768","url":null,"abstract":"<div><p>This study describes the anthelmintic efficacy of an organic fraction (EtOAc-F) from <em>Guazuma ulmifolia</em> leaves and the evaluation of its reactive oxidative stress on <em>Haemonchus contortus</em>. The first step was to assess the anthelmintic effect of EtOAc-F at 0.0, 3.5, 7.0 and 14 mg kg of body weight (BW) in gerbil's (<em>Meriones unguiculatus</em>) artificially infected with <em>H. contortus</em> infective larvae (L3). The second step was to evaluate the preliminary toxicity after oral administration of the EtOAc-F in gerbils. Finally, the third step was to determine the relative expression of biomarkers such as glutathione (GPx), catalase (CAT), and superoxide dismutase (SOD) against <em>H. contortus</em> L3 post-exposition to EtOAc-F. Additionally, the less-polar compounds of EtOAc-F were identified by gas mass spectrophotometry (GC-MS). The highest anthelmintic efficacy (97.34%) of the organic fraction was found in the gerbils treated with the 14 mg/kg of BW. Histopathological analysis did not reveal changes in tissues. The relative expression reflects overexpression of GPx (p&lt;0.05, fold change: 14.35) and over expression of SOD (p≤0.05, fold change: 0.18) in <em>H. contortus</em> L3 exposed to 97.44 mg/mL of EtOAc-F compared with negative control. The GC-MS analysis revealed the presence of 4-hydroxybenzaldehyde (<strong>1</strong>), leucoanthocyanidin derivative (<strong>2</strong>), coniferyl alcohol (<strong>3</strong>), ferulic acid methyl ester acetate (<strong>4</strong>), 2,3,4-trimethoxycinnamic acid (<strong>5</strong>) and epiyangambin (<strong>6</strong>) as major compounds. According to these results, the EtOAc-F from <em>G. ulmifolia</em> leaves exhibit anthelmintic effect and increased the stress biomarkers on <em>H. contortus.</em></p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108768"},"PeriodicalIF":2.1,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014489424000717/pdfft?md5=c64cd27215a93bba4648e4054fb65894&pid=1-s2.0-S0014489424000717-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive components in Psidium guajava extracts elicit biotoxic attributes and distinct antioxidant enzyme modulation in the larvae of vectors of lymphatic filariasis and dengue","authors":"Harun K. Aremu ,&nbsp;Olu I. Oyewole ,&nbsp;Adeola Adenmosun ,&nbsp;Lateefah Oyafajo ,&nbsp;Zarat O. Iwalewa ,&nbsp;Adenike Ademola ,&nbsp;Luqmon A. Azeez ,&nbsp;Monsuru A. Adeleke","doi":"10.1016/j.exppara.2024.108766","DOIUrl":"10.1016/j.exppara.2024.108766","url":null,"abstract":"<div><p>Control of mosquito vectors, which have caused a global disease burden, has employed various methods. However, the challenges posed by current physical and chemical methods have raised concerns about vector control programs, leading to the search for alternative methods that are less toxic, eco-friendly, and cost-effective. This study investigated the larvicidal potential of aqueous, methanol, and ethylacetate extracts of Guava (<em>Psidium guajava</em>) against <em>Aedes aegypti</em> and <em>Culex quinquefasciatus</em> larvae. Functional group and phytochemical characterization were performed using Fourier-Transform Infrared Spectroscopy (FTIR) and GC-MS analysis to identify the bioactive compounds in the extracts. Larval bioassays were conducted using WHO standard procedures at concentrations of 12.5, 25, 50, 125, and 250 mg/L, and mortality was recorded after 24, 48, and 72 h. Additionally, antioxidant enzyme profiles in the larvae were studied. All of the solvent extracts showed larvicidal activity, with the methanol extract exhibiting the highest mortality against <em>Ae. aegypti</em> and <em>Cx. quinquefasciatus</em> larvae, followed by aqueous and ethylacetate extracts. FTIR spectroscopic analysis revealed the presence of OH, C–H of methyl and methylene, C<img>O and C<img>C. The GC-MS analysis indicated that the methanol, aqueous, and ethylacetate extracts all had 27, 34, and 43 phytoactive compounds that were effective at causing larvicidal effects, respectively. Different concentrations of each extract significantly modulated the levels of superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione in larvae. This study's findings indicate the potential for developing environmentally friendly vector control products using the bioactive components of extracts from <em>P. guajava</em> leaves.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108766"},"PeriodicalIF":2.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxfendazole Nitazoxanide combination in experimental neurocysticercosis – Anti-inflammatory and cysticidal effects","authors":"Jefferson Aber Alves Araújo,&nbsp;Taynara Cristina Gomes,&nbsp;Vanessa Cindy Neres Lima,&nbsp;Yngrid Batista da Silva,&nbsp;Ruy de Souza Lino Junior,&nbsp;Marina Clare Vinaud","doi":"10.1016/j.exppara.2024.108764","DOIUrl":"10.1016/j.exppara.2024.108764","url":null,"abstract":"<div><p>Neurocysticercosis (NCC) is a parasitic infection caused by the larval stage of the pork tapeworm, <em>Taenia solium</em>. The complications of NCC include seizures, headaches, cognitive impairment, and focal neurological deficits. In addition to antiparasitic drugs and surgery, the management of NCC includes the use of corticosteroids to reduce inflammation and control symptoms. The traditional treatment with albendazole and praziquantel has not been altered over 30 years and present several side effects. There are other anti-helminthic drugs such as oxfendazole and nitazoxanide that may show efficacy in NCC treatment. The aim of this study was to determine the histopathologic aspects of experimental NCC after <em>in vivo</em> treatment with the combination of oxfendazole and nitazoxanide. Balb/c mice were infected with <em>T. crassiceps</em> cysticerci and divided into groups of 10 animals each that received a single dose through gavage as follows: group treated with NaCl 0.9% (control group); group treated by monotherapy of the anti-helminthic drugs, 30 mg/kg in single dose of oxfendazole (OXF) or nitazoxanide (NTZ); and groups treated with the combination of the drugs (OXF/NTZ group). Macroscopic and microscopic analysis were performed. There was greater presence of final stage cysticerci after treatment. The microscopic analysis of the general pathological processes showed that the monotherapy with all treatment groups induced higher perivasculitis than what was observed in the control group. In contrast, the combination treatment showed a lower observation of PMN and MN inflammatory infiltration in comparison to the other treatments and to the control one. These results show that indeed the association of benzimidazole derivatives which present both anti-helminthic and anti-inflammatory properties with other cysticidal drugs are beneficial for the NCC treatment in which the aim is to destroy parasite without inducing inflammatory damage in the brain tissue.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"262 ","pages":"Article 108764"},"PeriodicalIF":2.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlations between the degree of infection by wild strain of Toxoplasma gondii in vitro and porcine hematological parameters","authors":"Carlos Vinicius Barros Oliveira ,&nbsp;Maria Elenilda Paulino da Silva ,&nbsp;Jailson Renato de Lima ,&nbsp;Amanda Maria Tavares Moreira ,&nbsp;Maria Jéssica Mendes Brito ,&nbsp;Cicera Alane Coelho Gonçalves ,&nbsp;João Eudes Lemos de Barros ,&nbsp;Romário Matheus de Oliveira ,&nbsp;Jean Paul Kamdem ,&nbsp;Luiz Marivando Barros ,&nbsp;Antonia Eliene Duarte","doi":"10.1016/j.exppara.2024.108754","DOIUrl":"https://doi.org/10.1016/j.exppara.2024.108754","url":null,"abstract":"<div><p>The apicomplexa <em>Toxoplasma gondii</em> is capable of actively proliferating in numerous types of nucleated cells, and therefore has a high potential for dissemination and resistance. Thus, the present work aimed to correlate the inoculum concentrations and amount of post-infection parasites with porcine hematological parameters (including biochemistry) through <em>in vitro</em> culture. Porcine blood was incubated with different concentrations of parasites (1.2 × 10⁷, 6/3/1.5 × 10⁶ cells/mL), then the concentrations of red blood cells (RBC) and their morphology, total and differential leukocytes, and free peptides were evaluated. In addition, eight different blood samples analyzed before inoculation, where subsequent multivariate analysis was applied to correlate different variables with trophozoite concentration. The results showed no significant variation (p &lt; 0.05) in the relative levels of free peptides, or the relative percentage of RBC at all the parasite concentrations tested. However, the normalized percentages of leukocytes and neutrophils showed a significant reduction, while those of lymphocytes, eosinophils and monocytes showed the opposite behavior. Semi-automatic processing of images exhibited significant microcytosis and hypochromia. The multivariate analysis revealed a positive correlation between the amount number of protozoa (AP) and the variables: “Red cells” and “Neutrophils”, an indifference between the AP and the content of free peptides, and the concentration of monocytes in the samples; and a negative correlation for AP and the percentages of lymphocytes and eosinophils. Our results suggest that specific changes in hematological parameters may be associated with different degrees of parasitemia, demanding a thorough diagnostic process and adequate treatment.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108754"},"PeriodicalIF":2.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects of using sodium hypochlorite (bleach) and desiccation in surface inactivation for Toxocara spp","authors":"Janice L. Liotta ,&nbsp;Alexandra Helfer ,&nbsp;Lucy Huang ,&nbsp;Timothy Wu ,&nbsp;Dwight D. Bowman ,&nbsp;Carlo Castillo ,&nbsp;Hussni O. Mohammed ,&nbsp;Bryant S. Blank","doi":"10.1016/j.exppara.2024.108753","DOIUrl":"10.1016/j.exppara.2024.108753","url":null,"abstract":"<div><p><em>Toxocara cati</em> and <em>T. canis</em> are parasitic nematodes found in the intestines of cats and dogs respectively, with a cosmopolitan distribution, and the potential for anthropozoonotic transmission, resulting in human toxocariasis. Spread of <em>Toxocara</em> spp. is primarily through the ingestion of embryonated eggs contaminating surfaces or uncooked food, or through the ingestion of a paratenic host containing a third-stage larva. The <em>Toxocara</em> spp. eggshell is composed of a lipid layer providing a permeability barrier, a chitinous layer providing structural strength, and thin vitelline and uterine layers, which combined create a biologically resistant structure, making the <em>Toxocara</em> spp. egg very hardy, and capable of surviving for years in the natural environment. The use of sodium hypochlorite, household bleach, as a disinfectant for <em>Toxocara</em> spp. eggs has been reported, with results varying from ineffective to limited effectiveness depending on parameters including contact time, concentration, and temperature. Desiccation or humidity levels have also been reported to have an impact on larval development and/or survival of <em>Toxocara</em> spp. eggs. However, to date, after a thorough search of the literature, no relevant publications have been found that evaluated the use of sodium hypochlorite and desiccation in combination. These experiments aim to assess the effects of using a combination of desiccation and 10% bleach solution (0.6% sodium hypochlorite) on fertilized or embryonated eggs of <em>T</em>. <em>cati, T. canis,</em> and <em>T. vitulorum</em>. Results of these experiments highlight the synergistic effects of desiccation and bleach, and demonstrate a relatively simple method for surface inactivation, resulting in a decrease in viability or destruction of <em>T. cati</em>, <em>T. canis</em> and <em>T. vitulorum</em> eggs. Implications for these findings may apply to larger scale elimination of ascarid eggs from both research, veterinary, and farming facilities to mitigate transmission.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108753"},"PeriodicalIF":2.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140764016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteropathogenic Escherichia coli modulates the virulence and pathogenicity of Entamoeba dispar","authors":"Cezar Augusto Vilela da Silva ,&nbsp;Carlos Eduardo Costa dos Santos ,&nbsp;Mariana Fernandes de Paula Cortezzi ,&nbsp;César da Silva Santana Moura ,&nbsp;Ruth Elizabeth Cruz ,&nbsp;Camila de Almeida Lopes ,&nbsp;Karen Costa ,&nbsp;Lucas Teixeira de Souza ,&nbsp;Patrícia Costa Lima da Silva ,&nbsp;Elisabeth Neumann ,&nbsp;Álvaro Cantini Nunes ,&nbsp;Maria Aparecida Gomes ,&nbsp;Fabrício Marcus Silva Oliveira ,&nbsp;Marcelo Vidigal Caliari","doi":"10.1016/j.exppara.2024.108750","DOIUrl":"https://doi.org/10.1016/j.exppara.2024.108750","url":null,"abstract":"<div><p>Amoebiasis is a disease caused by <em>Entamoeba histolytica</em>, affecting the large intestine of humans and occasionally leading to extra-intestinal lesions. <em>Entamoeba dispar</em> is another amoeba species considered commensal, although it has been identified in patients presenting with dysenteric and nondysenteric colitis, as well as amoebic liver abscess. Amoebic virulence factors are essential for the invasion and development of lesions. There is evidence showing that the association of enterobacteria with trophozoites contributes to increased gene expression of amoebic virulence factors. Enteropathogenic <em>Escherichia coli</em> is an important bacterium causing diarrhea, with high incidence rates in the world population, allowing it to interact with <em>Entamoeba</em> sp. in the same host. In this context, this study aims to evaluate the influence of enteropathogenic <em>Escherichia coli</em> on ACFN and ADO <em>Entamoeba dispar</em> strains by quantifying the gene expression of virulence factors, including galactose/N-acetyl-D-galactosamine-binding lectin, cysteine proteinase 2, and amoebapores A and C. Additionally, the study assesses the progression and morphological aspect of amoebic liver abscess and the profile of inflammatory cells. Our results demonstrated that the interaction between EPEC and ACFN <em>Entamoeba dispar</em> strains was able to increase the gene expression of virulence factors, as well as the lesion area and the activity of the inflammatory infiltrate. However, the association with the ADO strain did not influence the gene expression of virulence factors. Together, our findings indicate that the interaction between EPEC, ACFN, and ADO <em>Entamoeba dispar</em> strains resulted in differences <em>in vitro</em> and <em>in vivo</em> gene expression of Gal/GalNAc-binding lectin and CP2, in enzymatic activities of MPO, NAG, and EPO, and consequently, in the ability to cause lesions.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108750"},"PeriodicalIF":2.1,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helminth-induced impairment of humoral immunity differently contribute to their anti-arthritic effects in mice: Comparison of Schistosoma mansoni and Trichinella spiralis","authors":"Yoshio Osada ,&nbsp;Shoichi Shimizu ,&nbsp;Kentaro Morita ,&nbsp;Eman M. Gaballah ,&nbsp;Zhiliang Wu ,&nbsp;Yoichi Maekawa","doi":"10.1016/j.exppara.2024.108752","DOIUrl":"https://doi.org/10.1016/j.exppara.2024.108752","url":null,"abstract":"<div><h3>Aims</h3><p>We have previously reported reduction of anti-type II collagen (IIC) IgG levels in collagen-induced arthritis (CIA) by <em>Schistosoma mansoni</em> (Sm) and <em>Trichinella spiralis</em> (Ts). To clarify the contribution of the impairment of humoral immunity to their anti-arthritic activities, we herein investigated the relationship between anti-IIC IgG levels and arthritic swelling in Sm- or Ts-infected mice.</p></div><div><h3>Methods and results</h3><p>Male DBA/1J mice were infected with Sm cercariae or Ts muscle larvae prior to the IIC immunization. In the Sm-infected mice, paw swelling and anti-IIC IgG levels were continuously lower than those of non-infected control group. In contrast, arthritic swelling in the Ts-infected mice only decreased in the early phase of CIA progression, despite the continued impairment of anti-IIC IgG production throughout the experimental period. Correlation coefficients between residual paw swelling and anti-IIC IgG titers were similar or higher in the Sm group than in the control group, but were similar or lower in the Ts group than in the control group.</p></div><div><h3>Conclusion</h3><p>The down-modulations of anti-IIC IgG levels by the two parasitic infections and the correlation analyses suggest that the anti-arthritic activity of Sm was primarily attributed to the modulation of IgG-independent arthritogenic mechanisms and secondarily to the impairment of anti-IIC IgG production. In contrast, Ts could alleviate CIA mainly via the impairment of antibody production.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108752"},"PeriodicalIF":2.1,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The response of Anisakis simplex (s. s.) to anthelmintics - Specific changes in xenobiotic metabolic processes","authors":"Robert Stryiński ,&nbsp;Iwona Polak ,&nbsp;Anna Gawryluk ,&nbsp;Paweł Rosa ,&nbsp;Elżbieta Łopieńska-Biernat","doi":"10.1016/j.exppara.2024.108751","DOIUrl":"https://doi.org/10.1016/j.exppara.2024.108751","url":null,"abstract":"<div><p>Anisakiasis is a parasitic disease transmitted through the consumption of raw or undercooked fish and cephalopods that are infected with larvae of <em>Anisakis simplex</em> (sensu stricto) or <em>Anisakis pegreffii</em>. The purpose of this study was to investigate how <em>A. simplex</em> (s. s.) responds to the influence of anthelmintics such as ivermectin (IVM) and pyrantel (PYR). <em>In vitro</em> experiments were conducted using larvae at two developmental stages of <em>A. simplex</em> (s. s.) (L3 and L4) obtained from Baltic herring (<em>Clupea harengus membras</em>). Larvae were cultured with different concentrations of IVM or PYR (1.56, 3.125, and 6.25 μg/mL) for various durations (3, 6, 9, and 12 h) under anaerobic conditions (37 °C, 5% CO₂). The gene expression of actin, ABC transporter, antioxidant enzymes, γ-aminobutyric acid receptors, and nicotinic acetylcholine receptors, as well as the oxidative status were analyzed. The results showed that <em>A. simplex</em> (s. s.) L3 stage had lower mobility when cultured with PYR compared to IVM. The analysis of relative gene expression revealed significant differences in the mRNA level of ABC transporters after treatment with IVM and PYR, compared to the control group. Similar patterns were observed in the gene expression of antioxidant enzymes in response to both drugs. Furthermore, the total antioxidant capacity (TAC) and glutathione S-transferase (GST) activity were higher in the treatment groups than in the control group. These findings suggest a relationship between the expression of the studied genes, including those related to oxidative metabolism, and the effectiveness of the tested drugs.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108751"},"PeriodicalIF":2.1,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trypanosoma cruzi killing and immune response boosting by novel phenoxyhydrazine-thiazole against Chagas disease","authors":"Ana Catarina Cristovão-Silva ,&nbsp;Maria Carolina Accioly Brelaz-de-Castro ,&nbsp;Elis Dionisio da Silva ,&nbsp;Ana Cristina Lima Leite ,&nbsp;Lizandra Beatriz Amorim Alves Santiago ,&nbsp;Juliana Maria da Conceição ,&nbsp;Robert da Silva Tiburcio ,&nbsp;Davi Pereira de Santana ,&nbsp;Danilo Cesar Galindo Bedor ,&nbsp;Breno Ítalo Valença de Carvalho ,&nbsp;Luiz Felipe Gomes Rebello Ferreira ,&nbsp;Rafael de Freitas e Silva ,&nbsp;Valéria Rêgo Alves Pereira ,&nbsp;Marcelo Zaldini Hernandes","doi":"10.1016/j.exppara.2024.108749","DOIUrl":"https://doi.org/10.1016/j.exppara.2024.108749","url":null,"abstract":"<div><p><em>Trypanosoma cruzi (T. cruzi)</em> causes Chagas, which is a neglected tropical disease (NTD). WHO estimates that 6 to 7 million people are infected worldwide. Current treatment is done with benznidazole (BZN), which is very toxic and effective only in the acute phase of the disease. In this work, we designed, synthesized, and characterized thirteen new phenoxyhydrazine-thiazole compounds and applied molecular docking and <em>in vitro</em> methods to investigate cell cytotoxicity, trypanocide activity, nitric oxide (NO) production, cell death, and immunomodulation. We observed a higher predicted affinity of the compounds for the squalene synthase and 14-alpha demethylase enzymes of <em>T. cruzi</em>. Moreover, the compounds displayed a higher predicted affinity for human TLR2 and TLR4, were mildly toxic <em>in vitro</em> for most mammalian cell types tested, and LIZ531 (IC50 2.8 μM) was highly toxic for epimastigotes, LIZ311 (IC50 8.6 μM) for trypomastigotes, and LIZ331 (IC50 1.9 μM) for amastigotes. We observed that LIZ311 (IC50 2.5 μM), LIZ431 (IC50 4.1 μM) and LIZ531 (IC50 5 μM) induced 200 μg/mL of NO and JM14 induced NO production in three different concentrations tested. The compound LIZ331 induced the production of TNF and IL-6. LIZ311 induced the secretion of TNF, IFNγ, IL-2, IL-4, IL-10, and IL-17, cell death by apoptosis, decreased acidic compartment formation, and induced changes in the mitochondrial membrane potential. Taken together, LIZ311 is a promising anti-<em>T. cruzi</em> compound is not toxic to mammalian cells and has increased antiparasitic activity and immunomodulatory properties.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108749"},"PeriodicalIF":2.1,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of bromocriptine and plumbagin against the monogenean Rhabdosynochus viridisi: Computational drug repositioning and in vitro approaches","authors":"Víctor Hugo Caña-Bozada ,&nbsp;Alejandra García-Gasca ,&nbsp;Juan M. Martínez-Brown ,&nbsp;F. Neptalí Morales-Serna","doi":"10.1016/j.exppara.2024.108748","DOIUrl":"https://doi.org/10.1016/j.exppara.2024.108748","url":null,"abstract":"<div><p>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 <em>Rhabdosynochus viridisi</em> (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). <em>In vitro</em> 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.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"261 ","pages":"Article 108748"},"PeriodicalIF":2.1,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}