The first comprehensive study of praziquantel effects in vivo and in vitro on European liver fluke Opisthorchis felineus (Trematoda)

Pakharukova, Maria Y.; Shilov, A. A.; Pirozhkova, Darya S.; Katokhin, Alexey V.; Mordvinov, Viatcheslav A.

doi:10.1016/j.ijantimicag.2015.02.012

Cited by 30 publications

(25 citation statements)

References 19 publications

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“…PZQ causes the loss of cellular permeability of the liver fluke, influx of Ca 2+ that induces tegumental vacuolizing, swelling, blebbing and finally tegumental disruption and musculature of the parasite [34]. Similar outcomes occur during infection with O. felineus [7]. The drug-damaged parasite is ultimately destroyed by the immune cells.…”

Section: Discussionmentioning

confidence: 99%

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Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model

Hanpanich

Laha

Sripa

et al. 2017

Parasitology International

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It has been suggested that repeated infection of Opisthorchis viverrini followed by repeated treatment with praziquantel (PZQ) increases risk of development of cholangiocarcinoma (CCA). Evidence for the prediction has accumulated based on findings of indirect approaches involving molecular changes and epidemiological trends. By contrast, here we directly monitored the impact of repeated liver fluke infection and treatment with PZQ on cholangiocarcinogenesis in a rodent model of human opisthorchiasis, using magnetic resonance imaging (MRI) and histopathology. Twenty five Syrian golden hamsters were assigned to five treatment groups: 1) infection with O. viverrini (OV group), 2) treatment with the carcinogen N-nitrosodimethylamine (NDMA) at 12.5 ppm (DMN), 3) O. viverrini infection in tandem with NDMA (OD), 4) O. viverrini infection, NDMA, and treatment with PZQ (ODP), and 5) uninfected, untreated control. The repeated infections were established by intragastric inoculation of 50 metacercariae of O. viverrini to the OV, OD and ODP hamsters at weeks 0, 5 and 10. PZQ at 300 mg/kg body weight was given to each hamster of the ODP group on weeks 4, 9 and 13 (four weeks after each infection). Imaging by MRI was undertaken on weeks 5, 10 and 14 (i.e. one week after each PZQ treatment). MRI revealed that the ODP hamsters did not develop CCA, whereas necropsy at week 40 revealed CCA in hamsters of the OD and DMN groups. Findings for histopathology and for proliferating cell nuclear antigen index conformed to the MRI findings. In overview, and notwithstanding that the immune response of individual hosts may play roles in cholangiocarcinogenesis, three cycles of the infection with O. viverrini followed treatment of the infection with PZQ did not increase the risk of bile duct cancer in this hamster model of liver fluke infection-induced CCA.

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Section: Discussionmentioning

confidence: 99%

“…Pakharukova et al [7] described a mechanism of anthelmintic action of PZQ against Opisthorchis felineus ; PZQ destroyed tegument and musculature of the parasite causing spasm, paralysis and death. It can be anticipated that PZQ acts similarly against O. viverrini [8].…”

Section: Introductionmentioning

confidence: 99%

Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model

Hanpanich

Laha

Sripa

et al. 2017

Parasitology International

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“…O. felineus metacercariae were collected from naturally infected fish ( Leuciscus idus ) caught in the Ob River near the city of Novosibirsk (Western Siberia) and extracted accordingly [22,23]. Territories where sample collection (fishing) took place were neither conservation areas nor private, nor otherwise protected; hence, no fishing permits were required.…”

Section: Methodsmentioning

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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“…According to the World Health Organization (WHO), the recommended dose of PZQ for opisthorchiasis is 75 mg/kg/day orally, three doses per day for two days, while for schistosomiasis it is 40 mg/kg per day divided in two doses for one day [62]. Some authors have suggested that worms have different susceptibilities to PZQ in geographically separated areas, even if they belong to the same species [63], therefore the dosages need to be adjusted according to where they are given. In general, these treatment schedules are well tolerated with only few mild and transient adverse events as abdominal pain, dizziness, headache, nausea and urticaria [64].…”

Section: Chemotherapy Against Schistosomiasis and Opisthorchiasismentioning

confidence: 99%

“…and Opisthorchis spp. newly excysted metacercariae (NEM) [63,66]. Although administration of PZQ might clear infection, PZQ alone cannot prevent or ameliorate infection-induced inflammation and fibrosis, and thus the risk factor for the infection-associated cancer remains following infection [61].…”

Section: Chemotherapy Against Schistosomiasis and 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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The first comprehensive study of praziquantel effects in vivo and in vitro on European liver fluke Opisthorchis felineus (Trematoda)

Cited by 30 publications

References 19 publications

Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model

Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model

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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