Cytochrome P450 in fluke Opisthorchis felineus: Identification and characterization

Pakharukova, Maria Y.; Ershov, Nikita I.; Vorontsova, Elena; Katokhin, Alexei V.; Merkulova, T. I.; Mordvinov, Viatcheslav A.

doi:10.1016/j.molbiopara.2011.11.005

Cited by 32 publications

(27 citation statements)

References 17 publications

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“…We found that, like flukes 23 , tapeworms typically have only one cytochrome P450 gene, suggesting their ability to oxidise many xenobiotics and steroids is substantially reduced compared to their hosts. Uniquely, tapeworms and flukes have merged two key enzymatic functions for redox homeostasis in one single enzyme: thioredoxin glutathione reductase (TGR).…”

Section: Reduced Metabolic Versatility and Specialised Detoxificationmentioning

confidence: 84%

The genomes of four tapeworm species reveal adaptations to parasitism

Tsai

Zarowiecki

Holroyd

et al. 2013

Nature

638

970

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Summary Tapeworms cause debilitating neglected diseases that can be deadly and often require surgery due to ineffective drugs. Here we present the first analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115-141 megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have species-specific expansions of non-canonical heat shock proteins and families of known antigens; specialised detoxification pathways, and metabolism finely tuned to rely on nutrients scavenged from their hosts. We identify new potential drug targets, including those on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.

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Section: Reduced Metabolic Versatility and Specialised Detoxificationmentioning

confidence: 84%

The genomes of four tapeworm species reveal adaptations to parasitism

Tsai

Zarowiecki

Holroyd

et al. 2013

Nature

638

970

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“…Furthermore, it is known that trematodes can produce specific genotoxic compounds, in particular, oxysterols and catecholestrogens, which are specific to some carcinogenic species of the trematodes: O. viverrini and Schistosoma haematobium [37,38]. The xenobiotic metabolizing enzymes of the parasites may participate in the synthesis of such compounds [39]. Additionally, biliary microbiota may also affect biliary diseases and CCA during infection with liver flukes [40,41].…”

Section: Discussionmentioning

confidence: 99%

Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters

Maksimova

Pakharukova

Кашина

et al. 2017

Parasitology International

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The food-borne liver trematode Opisthorchis felineus is an emerging source of biliary tract diseases on the territory of the former Soviet Union and Eastern Europe. This parasite along with trematodes Opisthorchis viverrini and Clonorchis sinensis belong to the triad of epidemiologically important liver flukes of the Opisthorchiidae family. It is known that O. viverrini and C. sinensis are the main risk factors of cholangiocarcinoma (CCA) in the endemic regions. The carcinogenic potential of O. felineus has not been well researched because of the absence of systematic pathomorphological, clinical, and epidemiological studies on O. felineus opisthorchiasis. In the present study, we show the results of detailed histopathological analysis and comprehensive evaluation of inflammation, bile duct dysplasia, periductal fibrosis, bile duct hyperplasia, bile duct proliferation, egg granuloma, cysts, cholangiofibrosis, and CCA from 10 to 30 weeks following infection of Syrian hamsters with O. felineus accompanied by oral administration of dimethylnitrosamine (DMN). The results revealed that O. felineus contributes to bile duct cancer development in the hamster model. During the combined action of O. felineus and DMN, morphological features of the liver underwent dramatic changes at the cellular and organ levels. Already in the early stages of the experiment, we observed extensive periductal fibrosis, active inflammation, proliferation of the bile duct, bile duct dysplasia and egg granulomas. Later, against the background of all these changes, cholangiofibrosis and CCA were found. Our work is the first step in the study of carcinogenic potential of O. felineus. Obtained data indicate the risk of CCA of patients having chronic O. felineus opisthorchiasis, and underscore the need for the development of programs for control of this helminthiasis.

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“…Recently, O. felineus cytochrome P450 was shown to be a promising target for the development of therapeutic agents against the disease. This enzyme is active in O. felineus tissues and it is crucial for the parasite survival [152,153]. Through analysis in vitro of anthelmintic activity of various CYP inhibitors using standard motility and mortality assays against juveniles and adult O. felineus, azole inhibitors were shown to reduce not only CYP activity but also substantially decrease the viability of the liver flukes [154].…”

Section: Opisthorchiasismentioning

confidence: 99%

Current and Novel Therapies Against Helminthic Infections: The Potential of Antioxidants Combined with Drugs

2020

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Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that might be considered as initiators of infection-associated carcinogenesis. Chemotherapy for these helminthic infections relies on a single drug, praziquantel, (PZQ) that mainly targets the parasite. Additionally, PZQ has some major drawbacks as inefficacy against juvenile form and alone it is not capable to counteract pathologies associated to infections or prevent carcinogenesis. There is an urgent need to develop novel therapeutic approaches that not only target the parasite but also improve the pathologies associated to infection, and ultimately, counteract or/and prevent the carcinogenesis processes. Repurposing the drug in combination of compounds with different modes of action is a promising strategy to find novel therapeutics approaches against these helminthic infections and its pathologies. Here, we emphasized that using antioxidants either alone or combined with anthelmintic drugs could ameliorate tissue damage, infection-associated complications, moreover, could prevent the development of cancer associated to infections. Hence, antioxidants represent a potential adjuvant approach during treatment to reduce morbidity and mortality. Despite the success of some strategies, there is a long way to go to implement novel therapies for schistosomiasis.

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Cytochrome P450 in fluke Opisthorchis felineus: Identification and characterization

Cited by 32 publications

References 17 publications

The genomes of four tapeworm species reveal adaptations to parasitism

The genomes of four tapeworm species reveal adaptations to parasitism

Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters

Current and Novel Therapies Against Helminthic Infections: The Potential of Antioxidants Combined with Drugs

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