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Effectiveness of Repeated Administration of Praziquantel with Disodium Glycyrrhizinate and Two Enantiomers of Praziquantel on Opisthorchis felineus (Rivolta, 1884)

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Abstract

Background

Nowadays, it is still important to develop effective anti-opisthorchiasis agents. In this work, we tested a complex of praziquantel (PZQ) with a plant origin compound—disodium glycyrrhizinate—in the ratio 1:10 PZQ:Na2GA, containing 11-fold less of the active ingredient. Our aim was to study various ways to treat trematode Opisthorchis felineus with this complex in vitro. Additionally, an in vitro comparison of the anthelmintic action was made among racemic-PZQ, (R)-PZQ, and (S)-PZQ on juvenile and adult maritae of O. felineus.

Methods

Worms extracted from the hamsters were subjected to various regimens of administration of the complex: once a day for 3 days or three times within 1 day. Moreover, mature maritae and juvenile worms of O. felineus were subjected to the comparison the anthelmintic effectiveness of racemic-PZQ, (R)-PZQ, and (S)-PZQ.

Results

The O. felineus maritae that received PZQ:Na2GA (1:10) thrice within 1 day were most strongly affected by the drug. Their motility substantially decreased already on the second day after the last dose, and the percentage of live worms by the end of the experimental period was the lowest. These results indicate a cumulative anthelmintic effect of this substance under the regimen “three times within 1 day.” For the first time, we report that among the three substances (racemic-PZQ and two enantiomers), (R)-PZQ has the highest anthelmintic activity, toward both juvenile and sexually mature maritae of O. felineus.

Conclusion

These findings suggest that the development of a supramolecular complex of (R)-PZQ with disodium glycyrrhizinate and administration of this complex three times within 1 day are promising approaches.

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Acknowledgements

The authors wish to thank the Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Higher Education and Science of Russian Federation (unique identifier of the project: RFMEFI 62117X 0015) for the provided Syrian hamsters (Mesocricetus auratus) with specific pathogen-free status. The study was supported by the Russian Foundation for Basic Research (grant No. 17-43-540175), state project of the ICG SB RAS (grant No. 0324-2019-0041), and state assignment for the Postovsky Institute of Organic Synthesis, UB RAS (topic No. AAAA-A19-119011790134-1).

Author information

Authors and Affiliations

  1. Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russian Federation

    D. F. Avgustinovich, M. A. Tsyganov, M. Y. Pakharukova & V. A. Mordvinov

  2. Institute of Solid State Chemistry and Mechanochemistry, SB RAS, Kutateladze Str. 18, Novosibirsk, 630128, Russian Federation

    D. F. Avgustinovich & A. V. Dushkin

  3. Novosibirsk State University, Pirogova Str. 10, Novosibirsk, 630090, Russian Federation

    M. A. Tsyganov

  4. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences (UB RAS), S. Kovalevskoy Str. 22/Academic Str. 20, Ekaterinburg, 620990, Russian Federation

    E. N. Chulakov & V. P. Krasnov

  5. National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China

    A. V. Dushkin

Authors
  1. D. F. Avgustinovich
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  2. M. A. Tsyganov
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  3. M. Y. Pakharukova
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  4. E. N. Chulakov
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  6. V. P. Krasnov
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  7. V. A. Mordvinov
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Contributions

DA: Conceived and designed the experiments, conducted the experiments, analyzed the data, and wrote the manuscript. MT: Conducted the in vitro experiments with complex PZQ:Na2GA. MP: Conducted the in vitro experiments with racemic-PZQ, (R)-PZQ, and (S)-PZQ. EC: Prepared the (R)- and (S)-enantiomers of PZQ. AD: Came up with the idea for the research, contributed reagents. VK: Prepared the (R)- and (S)-enantiomers of PZQ. VM: Came up with the idea for the research, conceived and designed the experiments, and revised the manuscript.

Corresponding authors

Correspondence to D. F. Avgustinovich or V. A. Mordvinov.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical consideration

All the animal experiments were conducted in compliance with the directives of the European Communities Council of 24 November 1986 (86/609/EEC) and according to the decision of the Ethics Committee of federal publicly funded scientific institution federal research center ICG SB RAS (decision # 39 of 27 September 2017).

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Avgustinovich, D.F., Tsyganov, M.A., Pakharukova, M.Y. et al. Effectiveness of Repeated Administration of Praziquantel with Disodium Glycyrrhizinate and Two Enantiomers of Praziquantel on Opisthorchis felineus (Rivolta, 1884). Acta Parasit. 65, 156–164 (2020). https://doi.org/10.2478/s11686-019-00149-2

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