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WormBook : the Online Review of C.... Nov 2007C. elegans is sensitive to the majority of anthelmintic drugs that are used against parasitic worm infections of humans and livestock. This has provided the opportunity... (Review)
Review
C. elegans is sensitive to the majority of anthelmintic drugs that are used against parasitic worm infections of humans and livestock. This has provided the opportunity to use molecular genetic techniques in the worm for mode of action studies. These approaches continue to be of considerable value to the field of parasitology. In addition, there are numerous examples of anthelmintic drugs providing exceptionally useful pharmacological tools to delineate fundamental aspects of cell signalling in C. elegans. This has primarily been achieved through the use of anthelmintics in forward genetic screens followed by the mapping and characterization of genes that confer altered susceptibility to the drug. Less fruitful so far, but nonetheless useful, has been the direct use of C. elegans for anthelmintic discovery programmes. In this brief review we provide an introduction to the use of C. elegans as a 'model parasite', outline the actions of the main classes of anthelmintics, and highlight approaches that have been of particular value.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Forecasting; Models, Animal
PubMed: 17988075
DOI: 10.1895/wormbook.1.143.1 -
Trends in Parasitology Sep 2021Most anthelmintics were discovered through in vivo screens using animal models of infection. Developing in vitro assays for parasitic worms presents several challenges.... (Review)
Review
Most anthelmintics were discovered through in vivo screens using animal models of infection. Developing in vitro assays for parasitic worms presents several challenges. The lack of in vitro life cycle culture protocols requires harvesting worms from vertebrate hosts or vectors, limiting assay throughput. Once worms are removed from the host environment, established anthelmintics often show no obvious phenotype - raising concerns about the predictive value of many in vitro assays. However, with recent progress in understanding how anthelmintics subvert host-parasite interactions, and breakthroughs in high-content imaging and machine learning, in vitro assays have the potential to discern subtle cryptic parasite phenotypes. These may prove better endpoints than conventional in vitro viability assays.
Topics: Animals; Anthelmintics; Drug Evaluation, Preclinical; Helminthiasis; Helminths; Host-Parasite Interactions
PubMed: 34092518
DOI: 10.1016/j.pt.2021.05.004 -
WormBook : the Online Review of C.... Dec 2014Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for... (Review)
Review
Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for agriculture. As such, these nematodes place a major burden on human health, on livestock production, on the welfare of companion animals and on crop production. In the 21st century there are two major challenges posed by the wide-spread prevalence of parasitic nematodes. First, many anthelmintic drugs are losing their effectiveness because nematode strains with resistance are emerging. Second, serious concerns regarding the environmental impact of the nematicides used for crop protection have prompted legislation to remove them from use, leaving agriculture at increased risk from nematode pests. There is clearly a need for a concerted effort to address these challenges. Over the last few decades the free-living nematode Caenorhabditis elegans has provided the opportunity to use molecular genetic techniques for mode of action studies for anthelmintics and nematicides. These approaches continue to be of considerable value. Less fruitful so far, but nonetheless potentially very useful, has been the direct use of C. elegans for anthelmintic and nematicide discovery programmes. Here we provide an introduction to the use of C. elegans as a 'model' parasitic nematode, briefly review the study of nematode control using C. elegans and highlight approaches that have been of particular value with a view to facilitating wider-use of C. elegans as a platform for anthelmintic and nematicide discovery and development.
Topics: Animals; Anthelmintics; Antinematodal Agents; Caenorhabditis elegans; Drug Evaluation, Preclinical; Helminthiasis; Humans; Models, Biological
PubMed: 25517625
DOI: 10.1895/wormbook.1.143.2 -
Molecules (Basel, Switzerland) Jul 2022Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined...
Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives - obtained during reactions of -substituted amidrazones with itaconic anhydride. Two groups of compounds, - and - differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives - and the anti-inflammatory activity of and - were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds and - was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives and - on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds - was studied in the sp. nematodes model. Most compounds (-) proved to be non-toxic to human PBMC. Derivatives - showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds and - significantly reduced the production of TNF-α and derivatives - decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound . Compounds and demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.
Topics: Anthelmintics; Anti-Infective Agents; Anti-Inflammatory Agents; Humans; Imidazoles; Leukocytes, Mononuclear; Sulfonamides; Thiophenes; Triazoles; Tumor Necrosis Factor-alpha
PubMed: 35889357
DOI: 10.3390/molecules27144488 -
PLoS Neglected Tropical Diseases Feb 2023Globally, helminth infections and cardiometabolic diseases often overlap in populations and individuals. Neither the causal relationship between helminth infections and...
BACKGROUND
Globally, helminth infections and cardiometabolic diseases often overlap in populations and individuals. Neither the causal relationship between helminth infections and cardiometabolic diseases nor the effect of helminth eradication on cardiometabolic risk have been reviewed systematically in a large number of human and animal studies.
METHODS
We conducted a systematic review assessing the reported effects of helminth infections and anthelmintic treatment on the development and/or severity of cardiometabolic diseases and risk factors. The search was limited to the most prevalent human helminths worldwide. This study followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42021228610). Searches were performed on December 10, 2020 and rerun on March 2, 2022 using Ovid MEDLINE ALL (1946 to March 2, 2022), Web of Science, Cochrane Library, Global Index Medicus, and Ovid Embase (1974 to March 2, 2022). Randomized clinical trials, cohort, cross-sectional, case-control, and animal studies were included. Two reviewers performed screening independently.
RESULTS
Eighty-four animal and human studies were included in the final analysis. Most studies reported on lipids (45), metabolic syndrome (38), and diabetes (30), with fewer on blood pressure (18), atherosclerotic cardiovascular disease (11), high-sensitivity C-reactive protein (hsCRP, 5), and non-atherosclerotic cardiovascular disease (4). Fifteen different helminth infections were represented. On average, helminth-infected participants had less dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. Eleven studies examined anthelmintic treatment, of which 9 (82%) reported post-treatment increases in dyslipidemia, metabolic syndrome, and diabetes or glucose levels. Results from animal and human studies were generally consistent. No consistent effects of helminth infections on blood pressure, hsCRP, or cardiac function were reported except some trends towards association of schistosome infection with lower blood pressure. The vast majority of evidence linking helminth infections to lower cardiometabolic diseases was reported in those with schistosome infections.
CONCLUSIONS
Helminth infections may offer protection against dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. This protection may lessen after anthelmintic treatment. Our findings highlight the need for mechanistic trials to determine the pathways linking helminth infections with cardiometabolic diseases. Such studies could have implications for helminth eradication campaigns and could generate new strategies to address the global challenge of cardiometabolic diseases.
Topics: Animals; Humans; Metabolic Syndrome; Cardiovascular Diseases; C-Reactive Protein; Cross-Sectional Studies; Anthelmintics; Helminthiasis; Helminths; Diabetes Mellitus
PubMed: 36827239
DOI: 10.1371/journal.pntd.0011022 -
International Journal For Parasitology.... Dec 2020For more than four decades, the free-living nematode Caenorhabditis elegans has been extensively used in anthelmintic research. Classic genetic screens and heterologous... (Review)
Review
For more than four decades, the free-living nematode Caenorhabditis elegans has been extensively used in anthelmintic research. Classic genetic screens and heterologous expression in the C. elegans model enormously contributed to the identification and characterization of molecular targets of all major anthelmintic drug classes. Although these findings provided substantial insights into common anthelmintic mechanisms, a breakthrough in the treatment and control of parasitic nematodes is still not in sight. Instead, we are facing increasing evidence that the enormous diversity within the phylum Nematoda cannot be recapitulated by any single free-living or parasitic species and the development of novel broad-spectrum anthelmintics is not be a simple goal. In the present review, we summarize certain milestones and challenges of the C. elegans model with focus on drug target identification, anthelmintic drug discovery and identification of resistance mechanisms. Furthermore, we present new perspectives and strategies on how current progress in C. elegans research will support future anthelmintic research.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Drug Discovery; Nematoda
PubMed: 33249235
DOI: 10.1016/j.ijpddr.2020.09.005 -
Biology Letters May 2022Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the... (Review)
Review
Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the conditions under which wild ruminants can act as a source of helminths (including anthelmintic-resistant genotypes) for domestic ruminants, and vice versa, with the added possibility that wildlife could act as for drug-susceptible genotypes and hence buffer the spread and development of resistance. Helminth infections cause significant productivity losses in domestic ruminants and a growing resistance to all classes of anthelmintic drug escalates concerns around helminth infection in the livestock industry. Previous research demonstrates that drug-resistant strains of the pathogenic nematode can be transmitted between wild and domestic ruminants, and that gastro-intestinal nematode infections are more intense in wild ruminants within areas of high livestock density. In this article, the factors likely to influence the role of wild ruminants in helminth infections and anthelmintic resistance in livestock are considered, including host population movement across heterogeneous landscapes, and the effects of climate and environment on parasite dynamics. Methods of predicting and validating suspected drivers of helminth transmission in this context are considered based on advances in predictive modelling and molecular tools.
Topics: Animals; Anthelmintics; Drug Resistance; Haemonchus; Livestock; Ruminants
PubMed: 35506237
DOI: 10.1098/rsbl.2022.0057 -
Trends in Parasitology Jun 2021Helminth secretomes comprise many potential immunomodulators. The molecular and functional diversity of these entities and their importance at the host-parasite... (Review)
Review
Helminth secretomes comprise many potential immunomodulators. The molecular and functional diversity of these entities and their importance at the host-parasite interface have been increasingly recognized. It is now common to hypothesize that parasite-derived molecules (PDMs) are essential mediators used by parasites to establish and remain in their hosts. Suppression of PDM release has been reported for two anthelmintic drug classes, the benzimidazoles and macrocyclic lactones, the mechanisms of action of which remain incompletely resolved. We propose that bringing together recent insights from different streams of parasitology research, for example, immunoparasitology and pharmacology, will stimulate the development of new ways to alter the host-parasite interface in the search for novel anthelmintic strategies.
Topics: Animals; Anthelmintics; Helminthiasis; Helminths; Host-Parasite Interactions
PubMed: 33563557
DOI: 10.1016/j.pt.2021.01.007 -
BMC Complementary Medicine and Therapies Jan 2023Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating...
BACKGROUND
Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating human trichinellosis, but with limited efficacy in killing the encysted larvae and numerous adverse effects. Cyperus rotundus L. is a herbal plant with a wide range of medicinal uses, including antiparasitic, and is frequently used in traditional medicine to treat various illnesses.
METHODS
LC-ESI-MS was used to identify the active phytoconstituents in the methanol extract (MeOH ext.) of the aerial parts of C. rotundus and its derivate fractions ethyl acetate (EtOAc fr.), petroleum ether (pet-ether fr.), and normal butanol (n-BuOH fr.). The in vivo therapeutic effects of C. rotundus fractions of the extracts were evaluated using the fraction that showed the most promising effect after detecting their in vitro anti-Trichinella spiralis potential.
RESULTS
C. rotundus extracts are rich in different phytochemicals, and the LC-ESI-MS of the 90% methanol extract identified 26 phenolic compounds classified as phenolic acids, flavonoids, and organic acids. The in vitro studies showed that C. rotundus extracts had a lethal effect on T. spiralis adults, and the LC were 156.12 µg/ml, 294.67 µg/ml, 82.09 µg/ml, and 73.16 µg/ml in 90% MeOH ext., EtOAc fr., pet-ether fr. and n-BuOH fr., respectively. The n-BuOH fr. was shown to have the most promising effects in the in vitro studies, which was confirmed by scanning electron microscopy. The in vivo effects of n-BuOH fr. alone and in combination with albendazole using a mouse model were evaluated by counting adults in the small intestine and larvae in the muscles, in addition to the histopathological changes in the small intestine and the muscles. In the treated groups, there was a significant decrease in the number of adults and larvae compared to the control group. Histopathologically, treated groups showed a remarkable improvement in the small intestine and muscle changes. Remarkably, maximal therapeutic effects were detected in the combination therapy compared to each monotherapy.
CONCLUSION
Accordingly, C. rotundus extracts may have anti-T. spiralis potential, particularly when combined with albendazole, and they may be used as synergistic to anti-T. spiralis medication therapy.
Topics: Humans; Albendazole; Plant Extracts; Cyperus; Methanol; Anthelmintics; Ethers
PubMed: 36658562
DOI: 10.1186/s12906-023-03839-7 -
Parasite (Paris, France) 2023
Topics: Animals; Ruminants; Anthelmintics; Drug Resistance
PubMed: 36762940
DOI: 10.1051/parasite/2023006