Effects of miconazole/clotrimazole and praziquantel combinations against the liver fluke Opisthorchis felineus in vivo and in vitro

Pakharukova, Maria Y.; Pakharukov, Yuri V.; Mordvinov, Viatcheslav A.

doi:10.1007/s00436-018-5895-6

Cited by 16 publications

(17 citation statements)

References 19 publications

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“…Similar findings were seen to those for TBD [147]. The synergistic effect of the PZQ-CTZ and PZQ-MCZ combinations observed in vitro, unfortunately were not evident in vivo [155]. For enhanced efficacy, different dosing ration or schedule may be necessary.…”

Section: Opisthorchiasissupporting

confidence: 72%

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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Section: Opisthorchiasissupporting

confidence: 72%

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

2020

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“…Another important motivation for using antioxidants as an adjunctive agent in a combination therapy is that in chronic opisthorchiasis, the accumulation of oxidative damage increases with the duration of infection and correlates with the disease severity [3,4]. Moreover, resolution of the pathological hepatobiliary changes is not seen in all cases after the flukes have been eliminated [5,10]. Unfortunately, these individuals may be at high risk of severe hepatobiliary sequelae including cholangiocarcinoma [5].…”

Section: Discussionmentioning

confidence: 99%

“…The current gold standard for measuring drug effectiveness for most helminth parasites is in vitro testing performed by microscopy, which included parasite counting and evaluation of motility and morphology [6,9,10,15]. Although reduced motility is not an ideal metric of mortality, it is a reasonable reduced viability analogue when screened for anthelmintic activity [6,9,10,15]. These assays of adult helminths revealed that antioxidants from both the natural set and synthetic set proved to be effective compounds (Table 1, Figure 2A).…”

Section: Motility Assaysmentioning

confidence: 99%

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Anthelmintic Activity of Antioxidants: In Vitro Effects on the Liver Fluke Opisthorchis felineus

et al. 2021

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Currently, molecular parasitologists are searching for new agents against trematodiases. Redox metabolism is important for parasites as far as long-lived adult parasites inside a mammalian host are exposed to redox challenges. Antioxidants have been poorly studied as anthelmintic agents, in particular against the foodborne trematodes. Study of in vitro anthelmintic activity of nonenzymatic natural and synthetic antioxidants of various chemical structures was performed using standard motility and mortality assays against juvenile and adult Opisthorchis felineus worms. Promising agents have been found among both natural and synthetic compounds. The mitochondria-targeted antioxidant SkQ1 [10-(6′-plastoquinonyl)decyltriphenylphosphonium] in motility assays was as effective (half-maximal inhibitory concentration [IC50] 0.6–1.4 μM) as praziquantel (IC50 0.47–1.4 μM), and SkQ1 was significantly more effective than praziquantel in mortality assays. Moreover, extensive tegument damage of the adult fluke was revealed after SkQ1 treatment. Flavonoids manifested potency too, with IC50 values in a micromolar range (5.1–17.4 μM). Other natural and synthetic compounds tested against helminths were significantly less effective than praziquantel. Results of our study indicate that SkQ1 and flavonoids have high anthelmintic activities against the liver flukes. We propose that structure–activity relationship research might be worthwhile based on the structures of the most effective substances.

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“…Worms remaining in the hepatobiliary system on day 14 post-treatment were counted after killing the hamsters by CO 2 asphyxiation. Drug activity was expressed as a worm burden reduction (WBR) as described elsewhere [8, 16]. Briefly, WBRs were calculated as follows: (a − b)/a × 100, where a is the average worm count in the control group upon dissection, and b is the average worm count in the treated group upon dissection.…”

Section: Methodsmentioning

confidence: 99%

A study of tribendimidine effects in vitro and in vivo on the liver fluke Opisthorchis felineus

et al. 2019

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BackgroundThe food-borne liver fluke Opisthorchis felineus is an epidemiologically important species and the causative agent of opisthorchiasis across an extensive territory of Eurasia. For decades, treatment of opisthorchiasis has been based on praziquantel. Tribendimidine could be an alternative drug that has been successfully tested for Opisthorchis viverrini and Clonorchis sinensis infections. We aimed to assess tribendimidine effects in comparison with praziquantel in vivo and in vitro against the liver fluke Opisthorchis felineus.ResultsIn this study we (i) calculated half-maximal inhibitory concentrations (IC50) by motility tests against O. felineus adults and newly excysted metacercarie after tribendimidine treatment in vitro; (ii) determined whether tribendimidine and PZQ effects on adult liver flukes are dependent on or mediated by white blood cells; and (iii) tested in vivo the anthelmintic activity of tribendimidine on juvenile and adult worms. We found that the efficiency of tribendimidine in vitro was similar (IC50 = 0.23 μM for newly excysted metacercariae and 0.19 μM for adult worms) to that of praziquantel (IC50 0.98 μM for newly excysted metacercariae and 0.47 μM for adult worms). The treatment of adult worms in vivo with praziquantel or tribendimidine at 400 mg/kg resulted in a 76% and 77.2% reduction, respectively, in the worm burden during chronic infection.ConclusionsThe differences between WBR values after PZQ and TBN treatment were not significant, thus tribendimidine was as effective as praziquantel against O. felineus liver flukes. Given the broad-spectrum activity of tribendimidine and efficacy against O. felineus, this drug may be a promising candidate for the treatment of opisthorchiasis felinea and other liver fluke infections.

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Effects of miconazole/clotrimazole and praziquantel combinations against the liver fluke Opisthorchis felineus in vivo and in vitro

Cited by 16 publications

References 19 publications

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

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

Anthelmintic Activity of Antioxidants: In Vitro Effects on the Liver Fluke Opisthorchis felineus

A study of tribendimidine effects in vitro and in vivo on the liver fluke Opisthorchis felineus

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