scholarly journals Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

2020 ◽  
Vol 1 ◽  
Author(s):  
Maria João Gouveia ◽  
Maria Y. Pakharukova ◽  
Gabriel Rinaldi ◽  
Viatcheslav A. Mordvinov ◽  
Paul J. Brindley ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Molecular Basis ◽  
Liver Fluke ◽  
Helminth Infection ◽  
Fasciola Hepatica ◽  
Dna Bases ◽  
Liquid Chromatography Mass Spectrometry ◽  
Food Borne ◽  
Liver Flukes ◽  
Compare And Contrast

AbstractEarlier reports revealed oxysterol metabolites of Opisthorchis spp. liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here, we employed liquid chromatography-mass spectrometry to investigate, compare and contrast spectrograms of soluble extracts from Fasciola hepatica adult worms from bile ducts of cattle with those from O. viverrini and O.felineus from experimentally infected hamsters. F. hepatica and Opisthorchis spp. shared common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of F. hepatica included far fewer compounds than Opisthorchis species. These findings support the postulate that parasitic oxysterol-like metabolites could be related to carcinogenesis associated to infection and they point to a molecular basis for the differences among major groups of liver flukes concerning infection-induced malignancy.

scholarly journals Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

2019 ◽  
Author(s):  
Maria João Gouveia ◽  
Maria Y. Pakharukova ◽  
Banchob Sripa ◽  
Gabriel Rinaldi ◽  
Paul J. Brindley ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Liver Fluke ◽  
Helminth Infection ◽  
Fasciola Hepatica ◽  
Clonorchis Sinensis ◽  
Opisthorchis Viverrini ◽  
International Agency ◽  
Fresh Water Fish ◽  
Liver Flukes ◽  
Group 1

AbstractChronic infections with the flatworm parasites Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are classified as group 1 biological carcinogens, i.e. definitive causes of cancer. In addition, we reported findings that support the inclusion of Opisthorchis felineus in this list of biological carcinogens. By contrast, infections with close phylogenetic relatives including Fasciola hepatica have not been associated with carcinogenesis. Earlier reports revealed of oxysterol metabolites of Opisthorchis liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here we employed liquid chromatography-mass spectrometry (LC-MS/MS) to investigate, compare and contrast spectrograms of soluble extracts from F. hepatica adult worms from bile ducts of cattle with those from O. viverrini and O. felineus from experimentally-infected hamsters. F. hepatica displayed a complex spectrophotometric profile. F. hepatica and Opisthorchis spp. shared several common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of these Opisthorchis species included far fewer compounds than F. hepatica. These findings support the postulate that oxysterol-like metabolites of parasite origin can initiate carcinogenesis and they point to a molecular basis for the inconsistencies among major groups of liver flukes concerning infection-induced malignancy.Author SummarySeveral species of trematodes are parasites of the human hepatobiliary tract. Infection with two of these flukes, Clonorchis sinsensis and Opisthorchis viverrini, fresh water fish-borne parasites that occur in East Asia is classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC), i.e. definitive causes of cancer in humans. By contrast, infection with a different liver fluke, Fasciola hepatica, does not lead to malignant transformation of the biliary tract. Given the close phylogeny of all three parasites, this difference in carcinogenicity is intriguing and, if explained, likely of value in novel therapeutic approaches. The importance of the current findings is informative because they present a mass spectrometric analysis and catalog of the similarities and differences between fluke of the genus Opisthorchis and F. hepatica, potentially identifying carcinogenic metabolites of liver fluke origin. These metabolites can be expected to provide deeper understanding of helminth infection induced malignancy.

Characterisation of two calmodulin-like proteins from the liver fluke, Fasciola hepatica

2007 ◽  
Vol 388 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Sean L. Russell ◽  
Neil V. McFerran ◽  
Elizabeth M. Hoey ◽  
Alan Trudgett ◽  
David J. Timson
Keyword(s):  
Metal Binding ◽  
Metal Ion ◽  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Expression Vectors ◽  
Metal Ion Binding ◽  
Ion Sensing ◽  
Calcium Magnesium ◽  
Ion Binding Sites ◽  
Liver Flukes

Abstract Calmodulin is a calcium ion-sensing signalling protein found in eukaryotics. Two calmodulin-like gene sequences were identified in an EST library from adult liver flukes. One codes for a protein (FhCaM1) homologous to mammalian calmodulins (98% identity), whereas the other protein (FhCaM2) has only 41% identity. These genes were cloned into expression vectors and the recombinant proteins were expressed in Escherichia coli. Gel shift assays showed that both proteins bind to calcium, magnesium and zinc ions. Homology models have been built for both proteins. As expected, FhCaM1 has a highly similar structure to other calmodulins. Although FhCaM2 has a similar fold, its surface charge is higher than FhCaM1. One of the potential metal ion-binding sites has lower metal-ion co-ordination capability, while another has an adjacent lysine residue, both of which may decrease the metal-binding affinity. These differences may reflect a specialised role for FhCaM2 in the liver fluke.

scholarly journals In vitro and in vivo trematode models for chemotherapeutic studies

Parasitology ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 589-603 ◽  
Author(s):  
J. KEISER
Keyword(s):  
Liver Fluke ◽  
Fasciola Hepatica ◽  
State Of The Art ◽  
Parasitic Diseases ◽  
Current State ◽  
Food Borne ◽  
Essential Components ◽  
Discovery Pipeline

SUMMARYSchistosomiasis and food-borne trematodiases are chronic parasitic diseases affecting millions of people mostly in the developing world. Additional drugs should be developed as only few drugs are available for treatment and drug resistance might emerge. In vitro and in vivo whole parasite screens represent essential components of the trematodicidal drug discovery cascade. This review describes the current state-of-the-art of in vitro and in vivo screening systems of the blood fluke Schistosoma mansoni, the liver fluke Fasciola hepatica and the intestinal fluke Echinostoma caproni. Examples of in vitro and in vivo evaluation of compounds for activity are presented. To boost the discovery pipeline for these diseases there is a need to develop validated, robust high-throughput in vitro systems with simple readouts.

scholarly journals Adenomatous Cholecystitis in Cattle with Chronic Fascioliasis

1974 ◽  
Vol 11 (5) ◽  
pp. 407-416 ◽  
Author(s):  
A. H. Cheema
Keyword(s):  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Inflammatory Cells ◽  
Fasciola Gigantica ◽  
Clinical Effects ◽  
Fibrous Stroma ◽  
Submucosal Glands ◽  
Glandular Structures ◽  
Mitotic Figures ◽  
Liver Flukes

Gall bladders from 80 mature cattle infested with liver flukes were shrunken; their walls were thickened; and mucosa was raised into rugose folds, nodules and papillary projections. All contained thick bile and mature liver flukes, predominantly Fasciola gigantica and to a lesser extent Fasciola hepatica. There was an adenomatous proliferation of the lining epithelium as well as of submucosal glands forming numerous tubuloalveolar structures and cysts lined with a uniform layer of columnar epithelium. Fibrous stroma was more than normal, and there was a mild to heavy infiltration by inflammatory cells. Some bladders had many enterochromaffin cells in the epithelium lining the glandular structures. Mitotic figures were rare, and there was no evidence of malignancy. The condition is inflammatory and hyperplastic and is believed to be common in cattle infested with liver fluke. The clinical effects of this condition have not been studied.

The excretory metabolism of the endoparasitic digenean Fasciola hepatica and its relationship to its respiratory metabolism

Parasitology ◽  
1970 ◽  
Vol 60 (1) ◽  
pp. 1-19 ◽  
Author(s):  
G. D. Moss
Keyword(s):  
Lactic Acid ◽  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Hymenolepis Diminuta ◽  
Respiratory Metabolism ◽  
Sheep Liver Fluke ◽  
Liver Flukes ◽  
Meat Market ◽  
Veterinary Officer

SUMMARYThe amounts of ammonia excreted by two endoparasitic flatworms have been compared and, weight for weight, the sheep liver fluke Fasciola hepatica produces ten times as much ammonia as the rat tapeworm Hymenolepis diminuta. This is thought to reflect a difference in diet, the fluke feeding mainly on the blood and tissue proteins of its host, and the tapeworm mainly on carbohydrates from the food materials in the gut of the host. However, the addition of glucose to the saline in which the flukes are cultured produces a marked decrease in the ammonia and an increase in the lactic acid excreted, suggesting that flukes are not obligatory protein feeders but that they may utilize carbohydrate when it is available. The relatively low production of lactic acid when proteins are being metabolized suggests that the flukes are producing an alternative end-product of respiratory metabolism. It is possible that this is the neutral lipid found in the excretory system of Fasciola and the possibility of an alternative metabolic pathway for the production of such lipid is discussed. The respiratory metabolism appears to be independent of oxygen, and the possible role of oxygen in other aspects of the metabolism of the fluke is discussed.I should like to express my sincere gratitude to Dr J. Llewellyn for his constant advice and encouragement during the course of this work and the preparation of the manuscript. I also thank Professor 0. E. Lowenstein, F.R.S., for allowing me the use of the facilities in his department during the tenure of an S.R.C. Research Studentship. Finally, my thanks are due to Mr E. Wilson, the Veterinary Officer at the Birmingham City Meat Market, for his constant co-operation in obtaining supplies of liver flukes.

scholarly journals Rumen (Calicophoron/Paramphistomum spp.) and Liver Flukes (Fasciola hepatica) in Cattle—Prevalence, Distribution, and Impact of Management Factors in Germany

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2727
Author(s):  
Tanja Forstmaier ◽  
Gabriela Knubben-Schweizer ◽  
Christina Strube ◽  
Yury Zablotski ◽  
Christoph Wenzel
Keyword(s):  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Animal Health ◽  
Parasitic Diseases ◽  
Northern Germany ◽  
Sedimentation Technique ◽  
Liver Flukes ◽  
First Time ◽  
Cattle Farms ◽  
Paramphistomum Leydeni

This study was carried out to determine the prevalence of rumen flukes on German cattle farms via the sedimentation technique, and to identify the rumen fluke species occurring in Germany. Additionally, the prevalence of patent Fasciola hepatica infections was determined. Furthermore, a short questionnaire was answered by the farmers. A prevalence of 5.5% and 9.5% was detected for rumen flukes and liver flukes, respectively. Coinfections occurred on 2.1% of farms. In northern Germany, the rumen fluke prevalence was higher than in southern Germany, while for liver fluke the distribution was reversed. Rumen flukes were mostly identified as Calicophoron daubneyi, but in four cases, sequencing revealed Paramphistomum leydeni for the first time in Germany. Grazing and feeding of fresh grass, as well as organic farming, were significantly associated with rumen and liver fluke occurrence. In contrast, suckler cow husbandry only had an influence on the occurrence of rumen flukes, but not liver flukes. Trematode eggs could be detected in both, farms with and without deworming. Since there were only a few studies about Paramphistomidosis in Germany, more attention should be paid to these parasitic diseases for animal welfare and animal health reasons.

Molecular evidence shows that the liver fluke Fasciola gigantica is the predominant Fasciola species in ruminants from Pakistan

2015 ◽  
Vol 90 (2) ◽  
pp. 206-213 ◽  
Author(s):  
U. Chaudhry ◽  
B. van Paridon ◽  
M.Z. Shabbir ◽  
M. Shafee ◽  
K. Ashraf ◽  
...  
Keyword(s):  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Fasciola Gigantica ◽  
Molecular Evidence ◽  
Human Populations ◽  
Rdna Its ◽  
Egg Morphology ◽  
Specialist Knowledge ◽  
Multiple Species ◽  
Liver Flukes

AbstractFascioliasis is an important disease affecting livestock, with great costs to producers worldwide. It has also become a serious issue for human populations in some endemic areas as an emerging zoonotic infection. There are two Fasciola species of liver fluke responsible for this disease, which occur worldwide, Fasciola hepatica and Fasciola gigantica. Identifying these two species on the basis of adult or egg morphology requires specialist knowledge due to the similarity of characters, and may misidentify putative intermediate or hybrid forms. In this study we sequenced the internal transcribed spacer 2 (ITS-2) rDNA of liver flukes collected from multiple species of hosts from seven localities in the Punjab and Baluchistan provinces of Pakistan, to determine the distribution of these two species. All 46 flukes processed in this study, collected from seven sites, showed the rDNA ITS-2 genotype corresponding to F. gigantica, contradicting previous reports, based on adult and egg morphology, that both species are present in Pakistan, with F. hepatica being the more common.

scholarly journals Identification of Somatic Antigens of Adult Fasciola gigantica Isolated from Bali Cattle

2021 ◽  
Vol 11 (1) ◽  
pp. 138-145
Author(s):  
Made Sriasih ◽  
Ahmad Munjizun
Keyword(s):  
Gel Electrophoresis ◽  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Fasciola Gigantica ◽  
Molecular Weights ◽  
Bos Javanicus ◽  
Antigenic Proteins ◽  
Bali Cattle ◽  
Liver Flukes ◽  
Somatic Extract

In most tropical countries, such as Indonesia, fasciolosis is generally caused by Fasciola gigantica known as tropical liver fluke. However, most fasciolosis serodiagnostic tests have been developed solely for diagnosing fasciolosis caused by Fasciola hepatica (non-tropical liver fluke), and very few have been specifically designed for F. gigantica. The aim of this study was to determine the profile of antigenic proteins from the somatic extract of F. gigantica isolated from Bali cattle (Bos javanicus). The liver flukes were collected from a slaughtering house in Mataram, Indonesia. The somatic extracts were prepared by homogenizing in buffers containing 0.05 M NaCl, 0.02 M PMSF, and 0.05% Triton X-100. The characterization of the somatic extract proteins was performed using one-dimension gel electrophoresis and followed by Western blotting to determine the profile of its antigenic proteins. There were 14 bands of the somatic extracts with an estimated molecular weight ranging from 8 to105 8 kDa shown on the gel electrophoresis. The results of the Western blot show that there were five prominent protein bands. Three out of five prominent antigenic proteins with molecular weights of 8, 27, and 33 kDa are promising to enrich the existence of antigens that have immunodiagnostic value for fasciolosis. Therefore, further studies are required to examine more deeply the potency of those three antigenic somatic proteins of F. gigantica.

scholarly journals The soluble glutathione transferase superfamily: role of Mu class in triclabendazole sulphoxide challenge in Fasciola hepatica

2021 ◽  
Vol 120 (3) ◽  
pp. 979-991
Author(s):  
Rebekah B. Stuart ◽  
Suzanne Zwaanswijk ◽  
Neil D. MacKintosh ◽  
Boontarikaan Witikornkul ◽  
Peter M. Brophy ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Liver Fluke ◽  
Glutathione Transferase ◽  
Fasciola Hepatica ◽  
Affinity Purification ◽  
Economic Loss ◽  
Differential Abundance ◽  
Parasitic Helminths

AbstractFasciola hepatica (liver fluke), a significant threat to food security, causes global economic loss for the livestock industry and is re-emerging as a foodborne disease of humans. In the absence of vaccines, treatment control is by anthelmintics; with only triclabendazole (TCBZ) currently effective against all stages of F. hepatica in livestock and humans. There is widespread resistance to TCBZ and its detoxification by flukes might contribute to the mechanism. However, there is limited phase I capacity in adult parasitic helminths with the phase II detoxification system dominated by the soluble glutathione transferase (GST) superfamily. Previous proteomic studies have demonstrated that the levels of Mu class GST from pooled F. hepatica parasites respond under TCBZ-sulphoxide (TCBZ-SO) challenge during in vitro culture ex-host. We have extended this finding by exploiting a sub-proteomic lead strategy to measure the change in the total soluble GST profile (GST-ome) of individual TCBZ-susceptible F. hepatica on TCBZ-SO-exposure in vitro culture. TCBZ-SO exposure demonstrated differential abundance of FhGST-Mu29 and FhGST-Mu26 following affinity purification using both GSH and S-hexyl GSH affinity. Furthermore, a low or weak affinity matrix interacting Mu class GST (FhGST-Mu5) has been identified and recombinantly expressed and represents a new low-affinity Mu class GST. Low-affinity GST isoforms within the GST-ome was not restricted to FhGST-Mu5 with a second likely low-affinity sigma class GST (FhGST-S2) uncovered. This study represents the most complete Fasciola GST-ome generated to date and has supported the potential of subproteomic analyses on individual adult flukes.

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