Effects of Three-time Administration of a Supramolecular Complex of Praziquantel with Disodium Glycyrrhizinate on Trematode Opisthorchis felineus in Hamsters

Abstract

Background

Praziquantel (PZQ) is the most commonly used anthelmintic drug for treating trematodiases. It was shown here that PZQ in complex with disodium glycyrrhizinate (PZQ-Na2GA, in the 1:10 ratio) has higher bioavailability than PZQ alone. Our aim was to determine the effects of three-time administration of PZQ-Na2GA in an experimental opisthorchiasis felinea model.

Methods

The PZQ-Na2GA complex (1:10) at a 400 mg/kg dose (meaning 36.4 mg/kg PZQ) was administered to Opisthorchis felineus-infected hamsters three times under a “9:00 am–6:00 pm–9:00 am” regimen (PZQ-Na2GA × 3). Effects of treatment were assessed as a reduction of helminth load in the hamsters and as changes in physiological, hematological, and blood biochemical parameters. The helminths extracted from the liver of the hamsters that received PZQ-Na2GA thrice were assayed for sensitivity to PZQ in vitro.

Results

PZQ-Na2GA × 3 reduced the number of O. felineus helminths in the liver by 87%, which is 30% better than a previously reported effect of one-time administration of the complex. Meanwhile, relative weights of the liver and thymus diminished, and some hematological parameters improved. The helminths extracted from the hamsters 1 month after the PZQ-Na2GA × 3 treatment showed elevated sensitivity to PZQ, as determined in vitro.

Conclusion

Compared with previously published data on the effectiveness of various drugs in experimental opisthorchiasis felinea, PZQ-Na2GA × 3 exerts the most potent anthelmintic effect. In addition, PZQ-Na2GA × 3 improves physiological status of O. felineus-infected hamsters and sensitizes the surviving parasites to subsequent PZQ treatment.

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Acknowledgments

The study was supported by the Russian Foundation for Basic Research (grant No. 20-04-00139) and a budget project of ICG SB RAS (grant No. 0324-2019-0041) as well as was implemented using the equipment of the Center for Genetic Resources of Laboratory Animals (ICG SB RAS) supported by the Ministry of Science and Higher Education of Russia (unique identifier of the project: RFMEFI62119X0023) and within the framework of a state assignment for ISSCM SB RAS (project No. 0301-2019-0005). The English language was corrected and certified by shevchuk-editing.com. (Language Certificate of December 7, 2020).

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Contributions

DA (avgust@bionet.nsc.ru) designed and conducted the experiments, analyzed the data, and wrote the manuscript. LM (lvovamaria@mail.ru) and MT (mtzygan@mail.ru) conducted the experiments with the animals and the biochemical assays. GV (wishn@mail.ru) conducted the experiments in vitro. IO (irorl@mail.ru), LT (toporkova12@mail.ru), and EG (l.goiman@mail.ru) performed the hematological analysis. AD (dushkin@solid.nsc.ru) and NL (lyakhov@solid.nsc.ru) came up with the idea for the research and developed the complex. VM (mordvin@bionet.nsc.ru) came up with the idea for the research, conceived and designed the experiments, and revised the manuscript.

Corresponding author

Correspondence to Damira Avgustinovich.

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The authors declare that they have no competing interests.

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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 the federal publicly funded scientific institution, federal research center ICG SB RAS (decision No. 39 of 27 September 2017).

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Avgustinovich, D., Lvova, M., Vishnivetskaya, G. et al. Effects of Three-time Administration of a Supramolecular Complex of Praziquantel with Disodium Glycyrrhizinate on Trematode Opisthorchis felineus in Hamsters. Acta Parasit. (2021). https://doi.org/10.1007/s11686-020-00329-5

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Keywords

  • Hamsters
  • Opisthorchis felineus
  • Praziquantel
  • Disodium glycyrrhizinate
  • In vitro