International Journal for Parasitology: Drugs and Drug Resistance最新文献

{"title":"Biotransformation of anthelmintics in nematodes in relation to drug resistance","authors":"Ondřej Vosála ,&nbsp;Josef Krátký ,&nbsp;Petra Matoušková ,&nbsp;Nikola Rychlá ,&nbsp;Karolína Štěrbová ,&nbsp;Lucie Raisová Stuchlíková ,&nbsp;Ivan Vokřál ,&nbsp;Lenka Skálová","doi":"10.1016/j.ijpddr.2025.100579","DOIUrl":"10.1016/j.ijpddr.2025.100579","url":null,"abstract":"<div><div>In all organisms, the biotransformation of xenobiotics to less toxic and more hydrophilic compounds represents an effective defense strategy. In pathogens, the biotransformation of drugs (used for their elimination from the host) may provide undesirable protective effects that could potentially compromise the drug's efficacy. Accordingly, increased drug deactivation via accelerated biotransformation is now considered as one of the mechanisms of drug resistance. The present study summarizes the current knowledge regarding the biotransformation of anthelmintics, specifically drugs used to treat mainly nematodes, a group of parasites that are a significant health concern for humans and animals. The main biotransformation enzymes are introduced and their roles in anthelmintics metabolism in nematodes are discussed with a particular focus on their potential participation in drug resistance. Similarly, the inducibility of biotransformation enzymes with sublethal doses of anthelmintics is presented in view of its potential contribution to drug resistance development. In the conclusion, the main tasks awaiting scientists in this area are outlined.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100579"},"PeriodicalIF":4.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitroxoline evidence amoebicidal activity against Acanthamoeba castellanii through DNA damage and the stress response pathways","authors":"Lijun Chen ,&nbsp;Wei Han ,&nbsp;Wenwen Jing ,&nbsp;Meng Feng ,&nbsp;Qingtong Zhou ,&nbsp;Xunjia Cheng","doi":"10.1016/j.ijpddr.2025.100578","DOIUrl":"10.1016/j.ijpddr.2025.100578","url":null,"abstract":"<div><div><em>Acanthamoeba castellanii</em> is a widespread unicellular eukaryote found in diverse environments, including tap water, soil, and swimming pools. It is responsible for severe infections, such as <em>Acanthamoeba</em> keratitis and granulomatous amebic encephalitis, particularly in individuals with immunocompromisation. The ability of protozoans to form dormant and persistent cysts complicates treatment, as current therapies are ineffective against cyst stages and suffer from poor specificity and side effects. Nitroxoline, a quinoline derivative with well-established antibacterial, antifungal, and antiviral properties, is a promising therapeutic candidate. This study aimed to elucidate cellular signalling events that counteract the effects of nitroxoline. In this study, nitroxoline significantly reduced the viability of <em>A</em>. <em>castellanii</em> trophozoites in a dose- and time-dependent manner, inducing morphological changes and apoptosis. Transcriptomic analysis revealed substantial alterations in gene expression, including enrichment of metabolic pathways, DNA damage responses, and iron ion binding. Nitroxoline treatment upregulated genes involved in DNA repair and oxidative stress response while regulating genes in the methionine and cysteine cycles. It also decreased the mitochondrial membrane potential, H₂S production, and total iron amount in <em>A</em>. <em>castellanii</em>. Bioinformatic analyses and molecular docking studies suggest direct interactions between nitroxoline and several <em>A</em>. <em>castellanii</em> proteins. Our research provides a comprehensive molecular map of the response of <em>A</em>. <em>castellanii</em> to nitroxoline, revealing significant changes in gene expression related to the stress response and metabolic pathways. These findings underscore the potential of nitroxoline as a potent anti-<em>Acanthamoeba</em> agent, offering new insights into its mechanism of action and paving the way for effective combinational therapeutic strategies.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100578"},"PeriodicalIF":4.1,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified dosing schedule efficacy of fosmidomycin and clindamycin against murine malaria Plasmodium berghei","authors":"Leah A. Walker,&nbsp;Vision Bagonza,&nbsp;Bryce Bobb,&nbsp;David J. Sullivan","doi":"10.1016/j.ijpddr.2024.100577","DOIUrl":"10.1016/j.ijpddr.2024.100577","url":null,"abstract":"<div><div>Fosmidomycin and clindamycin target the <em>Plasmodium</em> apicoplast. Combination clinical trials have produced mixed results with the primary problem being the recrudescent infection frequency by day 28. Given that antibiotic efficacy against bacterial infections often depends on the constant drug presence over several days, we hypothesized that the antimalarial blood or liver stage efficacy of fosmidomycin and clindamycin could be improved by implementing a more frequent dosing schedule. A blood stage murine malaria <em>P. berghei</em> GFP-luciferase low and high parasitemia model was implemented to follow pharmacodynamics and cure for modified dose, schedule and duration of individual and combination fosmidomycin and clindamycin. <em>P. berghei</em> sporozoites were used to investigate fosmidomycin during the 48 h murine liver stage. Here we observed that the same total dose of fosmidomycin and clindamycin, alone and in combination, are more efficacious when scheduled in smaller, more frequent doses. Fosmidomycin added measurably small additional killing in combination with clindamycin. Despite dosing every 6 h during liver stages, fosmidomycin was inhibitory, but noncurative even with addition of atorvastatin to decrease hepatocyte production of mevalonate. We have also demonstrated <em>in vitro</em> efficacy of fosmidomycin and clindamycin against <em>P. falciparum</em> C580Y with IC₅₀s similar to those for drug sensitive <em>P. falciparum</em>. The dosing schedule of quinoline and artemisinin partner drugs fosmidomycin or clindamycin targeting the apicoplast should maximize time above minimum inhibitory concentration.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100577"},"PeriodicalIF":4.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative DNA metabarcoding reveals species composition of a macrocyclic lactone and pyrantel resistant cyathostomin population in the UK","authors":"K.E. Bull ,&nbsp;J. Hodgkinson ,&nbsp;K. Allen ,&nbsp;J. Poissant ,&nbsp;L.E. Peachey","doi":"10.1016/j.ijpddr.2024.100576","DOIUrl":"10.1016/j.ijpddr.2024.100576","url":null,"abstract":"<div><div>Cyathostomins are the most abundant equid endoparasites globally. There are approximately fifty cyathostomin species and, whilst they occupy distinct niches within the large intestine, they are generally considered to share similar characteristics in terms of pathogenicity and response to drug treatment. There are three classes of anthelmintic licensed in the UK to treat cyathostomins (benzimidazoles, tetrahydropyrimidines and macrocyclic lactones) and cases of resistance have been documented for all classes. Previously, faecal egg count reduction tests (FECRT) on four UK Thoroughbred studs revealed multidrug resistant cyathostomins on one stud (A), with evidence of resistance to the macrocyclic lactones (MLs) ivermectin (IVM) and moxidectin (MOX), and to pyrantel (PYR). The remaining three studs (B-D) lacked resistance to IVM and MOX but had a shortened egg reappearance period post treatment.</div><div>To determine whether specific species could be associated with the observed resistance and shortened egg reappearance period, strongyle eggs collected from between six and 15 individual horses per stud were copro-cultured to third larval stage (L3), before and after anthelmintic treatment, over a three-year timeframe (2021–2023). Quantitative DNA metabarcoding of the ITS-2 region was carried out on all samples.</div><div>On stud A, single but differing species were found to be responsible for ML and pyrantel resistance in yearlings, <em>Cyathostomum catinatum</em> and <em>Cylicocyclus nassatus,</em> respectively. On studs B-D, with shortened egg reappearance periods, species composition remained largely unchanged post treatment.</div><div>This study is the first to quantitatively profile cyathostomin species composition pre- and post-treatment in a multidrug resistant population in the UK, revealing that resistance in cyathostomins was species specific. This raises the question of whether these species may be responsible for ML and PYR resistance more widely and indicates that anthelmintic resistance in cyathostomins may not be a multi-species phenomenon.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100576"},"PeriodicalIF":4.1,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury","authors":"Jing-Mei Lu ,&nbsp;Guang-Nan Jin ,&nbsp;Yan Xin ,&nbsp;Jing-Wen Ma ,&nbsp;Xin-Yu Shen ,&nbsp;Yan-Zhu Quan ,&nbsp;Yi-Ming Liu ,&nbsp;Jin-Yi Zhou ,&nbsp;Bing-Zhe Wang ,&nbsp;Ying-Biao Li ,&nbsp;Xiang Xu ,&nbsp;Lian-Xun Piao","doi":"10.1016/j.ijpddr.2024.100575","DOIUrl":"10.1016/j.ijpddr.2024.100575","url":null,"abstract":"<div><div><em>Toxoplasma gondii</em>, a neurotropic protozoan parasite, affects the central nervous system and causes various neurological disorders. Previous studies have demonstrated that Arctigenin (AG) exhibits anti-<em>T. gondii</em> activity and reduces depression-like behaviors induced by <em>T. gondii</em> infection. This study aimed to enhance AG's brain-targeting and therapeutic efficacy by developing lactoferrin-modified nanoemulsions loaded with AG (Lf-AG-NEs). Lf-modified nanoemulsions were prepared and assessed using <em>in vivo</em> and <em>in vitro</em> infection models with the <em>T. gondii</em> RH strain, and a co-culture system of BV2 microglia and primary neuron cells. The effects of Lf-AG-NEs on <em>T. gondii</em>-induced neuronal injury were examined, and potential molecular mechanisms were elucidated through real-time quantitative PCR, western blotting, immunofluorescence, flow cytometry, immunohistochemistry, and Nissl staining. <em>In vitro</em> assessments showed significant increases in cellular uptake and blood-brain barrier penetration by Lf-AG-NEs. These nanoemulsions notably inhibited <em>T. gondii</em> proliferation in brain tissue and BV2 cells, surpassing the effects of free AG or AG-NEs alone. Additionally, Lf-AG-NEs substantially alleviated neuropathological changes and reduced microglial activation and neuroinflammation by downregulating the TLR4/NF-κB and TNFR1/NF-κB signaling pathways. Co-culturing BV2 cells with primary cortical neurons indicated that Lf-AG-NEs, similarly to CLI-095 and R7050, attenuated <em>T. gondii</em>-induced microglial activation and subsequent neuronal injury. In conclusion, the successfully prepared Lf-AG-NEs not only enhanced the anti-<em>T. gondii</em> effect but also strengthened the protective impact against neuronal injury induced by <em>T. gondii</em>, through the modulation of microglial signaling pathways.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100575"},"PeriodicalIF":4.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The binuclear cyclopalladated complex CP2 is targeting ubiquinol-cytochrome c reductase (complex III) of Leishmania amazonensis","authors":"Angela Maria Arenas Velásquez ,&nbsp;Irwin Alexander Patino Linares ,&nbsp;Lawrence D. Gaspers ,&nbsp;Paula J. Bartlett ,&nbsp;Jecika M. Velasques ,&nbsp;Adelino V.G. Netto ,&nbsp;Andrew P. Thomas ,&nbsp;Marcia A.S. Graminha","doi":"10.1016/j.ijpddr.2024.100574","DOIUrl":"10.1016/j.ijpddr.2024.100574","url":null,"abstract":"<div><div>Leishmaniasis is a neglected disease that remains with a limited number of drugs available for chemotherapy and has an increased drug resistance that affects treatment outcomes. Metal-based drugs such as cyclopalladated complex [Pd(dmba)(μ-N₃)]₂ (<strong>CP2</strong>), a <em>Leishmania</em> topoisomerase IB inhibitor involved in calcium dysregulation and mitochondrial dysfunction of the parasite, had been an alternative to outline the appearance of chemoresistance. To identify new molecular targets and point out possible resistance mechanisms, a <strong>CP2</strong>-resistant <em>Leishmania amazonensis</em> (<em>LaR</em>) was selected by stepwise exposure to increasing drug pressure until a line capable of growth in 13.3 μM <strong>CP2</strong>. <em>LaR</em> IC₅₀ value was 52.4 μM (4-fold higher than <em>L. amazonensis</em>–wild type, <em>La</em>). <em>LaR</em> promastigotes were cross-resistant to other DNA topoisomerase I inhibitors (camptothecin) and more susceptible to anti-leishmanial drugs pentamidine and miltefosine. A protective effect on cell viability was observed by pretreating the parasite with Ca²⁺ channel blockers followed by <strong>CP2</strong> in <em>La</em> but not in <em>LaR</em>. Analyses of the cell viability of <em>La</em> and <em>LaR</em> using electron transport chain (ETC) inhibitors demonstrated that <em>La</em> is more sensitive than <em>LaR</em>. The studies of mitochondrial oxygen consumption demonstrated that <em>LaR</em> is less susceptible to complex III (ubiquinol-cytochrome <em>c</em> reductase – CcR) inhibitor, antimycin A (AA). CcR activities of <em>La</em> and <em>LaR</em> were equal for both strains in the absence of <strong>CP2</strong> and significantly decreased, 69 % for <em>La</em> and 51 % for <em>LaR</em>, in the presence of <strong>CP2</strong>. This resistance is attributed to overexpression of CcR, confirmed by the RT-qPCR. CcR inhibition by <strong>CP2</strong> leads the parasite to increase the reactive oxygen species (ROS) production, principally in <em>La.</em> Therefore, in this work, we suggested that CcR is the main target of <strong>CP2</strong> in the mitochondria, acting to inhibit mitochondria respiratory, and the <em>LaR</em> mutant has increased activity of CcR, which reduces the formation of ROS.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100574"},"PeriodicalIF":4.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Licochalcone a: A promising antiparasitic drug against giardiasis","authors":"Yingying Zhang ,&nbsp;Wenchao Zhao ,&nbsp;Haili Du ,&nbsp;Pitambar Dhakal ,&nbsp;Xinyi Chen ,&nbsp;Longfei Wu ,&nbsp;Xiaoying Li ,&nbsp;Rongjun Wang ,&nbsp;Longxian Zhang ,&nbsp;Sumei Zhang ,&nbsp;Junqiang Li","doi":"10.1016/j.ijpddr.2024.100573","DOIUrl":"10.1016/j.ijpddr.2024.100573","url":null,"abstract":"<div><div>Giardiasis, caused by <em>Giardia duodenalis</em>, is a prevalent and significant zoonotic disease. While nitroimidazole drugs are primarily used to treat giardiasis, the urgent need for the development and formulation of new drugs has arisen due to increasing drug resistance. Several plant derived medicine have been employed as antiparasitic drugs. This study has evaluated the anti-<em>Giardia</em> effect of Licochalcone A (Lic A) through both <em>in vitro</em> and <em>in vivo</em> experiments. We determined the 50% inhibitory concentration (IC₅₀) of Lic A, analyzed the adhesive ability of <em>G. duodenalis</em>, and assessed intestinal morphology and various indicators in the gerbil model. The <em>in vitro</em> assays demonstrated that the IC₅₀ value of Lic A against <em>G. duodenalis</em> was 27.42 μM. Additionally, Lic A significantly inhibited the adhesiveability of <em>G. duodenalis</em> trophozoites, impairing their cell structure and cytoskeleton. <em>In vivo</em> experiments showed that Lic A significantly mitigated weight loss due to <em>G. duodenalis</em> infection, and lowered the intestinal parasite load. Histopathological examinations in gerbils indicated that Lic A could reduce intestinal damage, increase the height of intestinal villi, decrease crypt depth, and maintain the integrity of intestinal structure. Furthermore, Lic A altered cytokine levels and enhanced the body's antioxidant capacity. In conclusion, Lic A exbibits significant anti-<em>Giardia</em> effects both <em>in vitro</em> and <em>in vivo</em>, suggesting its potential as a promising antiparasitic drug candidate against giardiasis.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100573"},"PeriodicalIF":4.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of fenbendazole against gastrointestinal nematodes in naturally infected goats in Maputo Province, Mozambique using in vivo, in vitro and molecular assessment","authors":"Edna F.X. Guinda ,&nbsp;Sonia M.S. Afonso ,&nbsp;Stefan Fiedler ,&nbsp;Eric R. Morgan ,&nbsp;Sabrina Ramünke ,&nbsp;Marc Borchert ,&nbsp;Alsácia Atanásio ,&nbsp;Bettencourt P.S. Capece ,&nbsp;Jürgen Krücken ,&nbsp;Georg von Samson-Himmelstjerna","doi":"10.1016/j.ijpddr.2024.100572","DOIUrl":"10.1016/j.ijpddr.2024.100572","url":null,"abstract":"<div><div>Anthelmintic resistance occurs worldwide in strongyles of ruminants but data from low-income countries are sparse and rarely apply most up to date methods, while effects of management practices in these countries are poorly documented. In Mozambique, benzimidazole resistance has been previously reported; the present study followed this up in detail, applying <em>in vivo</em> faecal egg count (FEC) reduction test (FECRT), <em>in vitro</em> egg hatch test (EHT) and molecular deep amplicon sequencing approaches targeting the internal transcribed spacer 2 (ITS-2, nemabiome) and the isotype 1 β-tubulin gene to determine the resistance status on farms and the strongyle species involved. Adult <em>Landim</em> goats (433) from six semi-intensive and ten extensive farms (22–30 animals/farm) from Maputo Province were visited April 2021 to February 2022. Fenbendazole (5 mg/kg bw, Panacur®) was administered orally and FEC determined using Mini-FLOTAC. The eggCounts package was used to calculate FECRs with 90% confidence intervals from paired day 0 and 14 data. <em>In vivo</em> and <em>in vitro</em> tests detected AR on 5/16 (31%) farms. This included 1/10 extensive and 4/6 semi-intensive farms. The odds of finding resistant strongyles on a semi-intensive commercial farm was 40-fold higher than on an extensive farm (p = 0.016, logistic regression). A strong, negative correlation was observed between FECRT and EHT EC₅₀ values (Pearson's R = −0.83, P = 0.001; Cohen's κ coefficient 1.0). Nemabiome data showed that <em>Haemonchus contortus</em>, <em>Trichostrongylus colubriformis</em> and unclassified <em>Oesophagostomum</em> closely related to <em>Oesophagostomum columbianum</em> were most abundant before treatment and in particular <em>H. contortus</em> frequencies increased after treatment. Benzimidazole resistance associated polymorphisms were detected in <em>H. contortus</em> and <em>T. colubriformis</em>. Moreover, there were hints that resistance alleles were present in <em>Trichostrongylus axei</em> and <em>Teladorsagia circumcincta</em>. Farmers should regularly test the efficacy of anthelmintics used and consider more sustainable worm control approaches to reduce selection for resistance.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100572"},"PeriodicalIF":4.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Efficacy of flukicides against Fasciola hepatica and first report of triclabendazole resistance on German sheep farms” [Int. J. Parasitol. Drugs Drug Resist. 23 (2023) 94–105]","authors":"Alexandra Kahl ,&nbsp;Georg von Samson-Himmelstjerna ,&nbsp;Christina Helm ,&nbsp;Jane Hodgkinson ,&nbsp;Diana Williams ,&nbsp;Wiebke Weiher ,&nbsp;Werner Terhalle ,&nbsp;Stephan Steuber ,&nbsp;Martin Ganter ,&nbsp;Jürgen Krücken","doi":"10.1016/j.ijpddr.2024.100562","DOIUrl":"10.1016/j.ijpddr.2024.100562","url":null,"abstract":"","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100562"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antileishmanial and synergic effects of Rhanterium epapposum essential oil and its main compounds alone and combined with glucantime against Leishmania major infection","authors":"Abdullah D. Alanazi ,&nbsp;Areej Jameel Alghabban","doi":"10.1016/j.ijpddr.2024.100571","DOIUrl":"10.1016/j.ijpddr.2024.100571","url":null,"abstract":"<div><div>Cutaneous leishmaniasis (CL) is a widespread disease affecting both humans and animals globally. Currently, common treatments (e.g., glucantime (GC) for CL treatment have many side effects that limit their use. The current experimental study aims to assess the <em>in vitro, in vivo</em>, and potential mechanisms of action of <em>Rhanterium epapposum</em> essential oil (REE) and its main compounds β-Myrcene (MC), camphene (CP), and limonene (LN) alone and in combination against <em>Leishmania major</em>. In vitro effects of REE and its main compounds were evaluated on amastigote forms, infection in macrophages cells stimulation of nitric oxide (NO), and stimulation of the cellular immunity in macrophages. In vivo efficacy of REE and its main constituents was also assessed in mice with CL through evaluating parasite burden, oxidative stress and proinflammatory-related genes. A concentration-dependent reduction in the average number of amastigotes was observed, with statistical significance (p &lt; 0.001); whereas the results revealed synergistic effects when REE, MC and LN were combined with GC. REE and main compounds mainly in combination elicited a dose-dependent elevation in NO production and the expression levels of inducible nitric oxide synthase (iNOS), interferon gamma (IFN-γ), and tumor necrosis factor (TNF-α) genes in macrophages. Notably, mice treated with a combination of REE, MC, and GC showed the complete recovery of CL lesions after 28 days of treatment and resulted in a reduction of tissue malondialdehyde levels and a significant increase (p &lt; 0.001) in the gene expression levels of the antioxidant enzymes. Topical treating CL-infected mice with REE and its main compounds alone particularly in conjunction with GC, significantly increased (p &lt; 0.001) the expression levels of IFN-γ and interleukin (IL-12), while also causing a notable reduction in IL-4 expression. The findings of the current experimental research revealed the high <em>in vitro</em> and <em>in vivo</em> antileishmanial efficacy of REE and its main compounds MC, CP, and LN mainly in combination with GC; which indicated the high synergic effects of these compounds.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"26 ","pages":"Article 100571"},"PeriodicalIF":4.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}