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

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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References

  1. 1.

    Alsaqabi SM, Lotfy WM (2014) Praziquantel: a review. J Veterinar Sci Technol 5(5):1–8. https://doi.org/10.4172/2157-7579.1000200

    CAS  Article  Google Scholar 

  2. 2.

    Avgustinovich D, Tsyganov M, Vishnivetskaya G, Kovner A, Sorokina I, Orlovskaya I, Toporkova L, Goiman E, Tolstikova T, Dushkin A, Lyakhov N, Mordvinov V (2019) Effects of supramolecular complexation of praziquantel with disodium glycyrrhizinate on the liver fluke Opisthorchis felineus: an in vitro and in vivo study. Acta Trop 194:1–12. https://doi.org/10.1016/j.actatropica.2019.03.017

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Baykova OA, Nikolaeva NN, Grishchenko EG, Nikolaeva LV (2017) Opisthorchiasis and clonorchiasis treatment: modern approach, concerns and perspectives. Health Educ Millenn 19(6):14–25 (in Russian)

    Google Scholar 

  4. 4.

    Borrego-Sánchez A, Carazo E, Albertini B, Passerini N, Perissutti B, Cerezo P, Viseras C, Hernández-Laguna A, Aguzzi C, Sainz-Díaz CI (2018) Conformational polymorphic changes in the crystal structure of the chiral antiparasitic drug praziquantel and interactions with calcium carbonate. Eur J Pharm Biopharm 132:180–191. https://doi.org/10.1016/j.ejpb.2018.09.028

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Buchter V, Hess J, Gasser G, Keiser J (2018) Assessment of tegumental damage to Schistosoma mansoni and S. haematobium after in vitro exposure to ferrocenyl, ruthenocenyl and benzyl derivatives of oxamniquine using scanning electron microscopy. Parasit Vectors 11(1):580. https://doi.org/10.1186/s13071-018-3132-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Cedillo-Cruz A, Aguilar MI, Flores-Alamo M, Palomares-Alonso F, Jung-Cook H (2014) A straightforward and efficient synthesis of praziquantel enantiomers and their 4′-hydroxy derivatives. Tetrahedron. Asymmetry 25(2):133–140. https://doi.org/10.1016/j.tetasy.2013.11.004

    CAS  Article  Google Scholar 

  7. 7.

    Chai JY (2013) Praziquantel treatment in trematode and cestode infections: an update. Infect Chemother 45(1):32–43. https://doi.org/10.3947/ic.2013.45.1.32

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Chou TC, Martin N (2005) CompuSyn for drug combinations: PC software and user’s guide: a computer program for quantitation of synergism and antagonism in drug combinations, and the determination of IC50 and ED50 and LD50 values. ComboSyn Inc, Paramus

    Google Scholar 

  9. 9.

    da Silva VBR, Campos BRKL, de Oliveira JF, Decout JL, de Lima MDCA (2017) Medicinal chemistry of antischistosomal drugs: praziquantel and oxamniquine. Bioorg Med Chem 25(13):3259–3277. https://doi.org/10.1016/j.bmc.2017.04.031

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Hong ST, Lee SH, Lee SJ, Kho WG, Lee M, Li S, Chung BS, Seo M, Choi MH (2003) Sustained-release praziquantel tablet: pharmacokinetics and the treatment of clonorchiasis inbeagle dogs. Parasitol Res 91(4):316–320. https://doi.org/10.1007/s00436-003-0958-7

    Article  PubMed  Google Scholar 

  11. 11.

    Kamsa-ard S, Laopaiboon M, Luvira V, Bhudhisawasdi V (2013) Association between praziquantel and cholangiocarcinoma in patients infected with Opisthorchis viverrini: a systematic review and meta-analysis. Asian Pac J Cancer Prev 14(11):7011–7016. https://doi.org/10.7314/apjcp.2013.14.11.7011

    Article  PubMed  Google Scholar 

  12. 12.

    Keiser J, Utzinger J (2010) The drugs we have and the drugs we need against major helminth infections. Adv Parasitol 73:197–230. https://doi.org/10.1016/S0065-308X(10)73008-6

    Article  PubMed  Google Scholar 

  13. 13.

    Kelly JW, He L, Stewart JT (1993) Liquid chromatographic separation of praziquantel enantiomers in serum using a cellulose-based chiral stationary phase. J Pharma Biomed Anal 11(11/12):1141–1144. https://doi.org/10.1016/0731-7085(93)80095-I

    CAS  Article  Google Scholar 

  14. 14.

    Kong R, Zhu X, Meteleva ES, Chistyachenko YS, Suntsova LP, Polyakov NE, Khvostov MV, Baev DS, Tolstikova TG, Yu J, Dushkin AV, Su W (2017) Enhanced solubility and bioavailability of simvastatin by mechanochemically obtained complexes. Int J Pharm 534(1–2):108–118. https://doi.org/10.1016/j.ijpharm.2017.10.011

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Kovač J, Vargas M, Keiser J (2017) In vitro and in vivo activity of R- and S-praziquantel enantiomers and the main human metabolite trans-4-hydroxy-praziquantel against Schistosoma haematobium. Parasit Vectors 10(1):365. https://doi.org/10.1186/s13071-017-2293-3

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Meister I, Ingram-Sieber K, Cowan N, Todd M, Robertson MN, Meli C, Patra M, Gasser G, Keiser J (2014) Activity of praziquantel enantiomers and main metabolites against Schistosoma mansoni. Antimicrob Agents Chemother 58(9):5466–5472. https://doi.org/10.1128/AAC.02741-14

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Meteleva ES, Chistyachenko YS, Suntsova LP, Khvostov MV, Polyakov NE, Selyutina OYu, Tolstikova TG, Frolova TS, Mordvinov VA, Dushkin AV, Lyakhov NZ (2019) Disodium salt of glycyrrhizic acid—a novel supramolecular delivery system for anthelmintic drug praziquantel. J Drug Deliv Sci Technol 50:66–77. https://doi.org/10.1016/j.jddst.2019.01.014

    CAS  Article  Google Scholar 

  18. 18.

    Meteleva ES, Chistyachenko YuS, Suntsova LP, Tsyganov MA, Vishnivetskaya GB, Avgustinovich DF, Khvostov MV, Polyakov NE, Tolstikova TG, Mordvinov VA, Dushkin AV, Lyakhov NZ (2018) Physicochemical properties and anti-opisthorchosis effect of mechanochemically synthesized solid compositions of praziquantel with glycyrrhizic acid disodium salt. Dokl Biochem Biophys 481(1):228–231. https://doi.org/10.1134/S1607672918040142

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Nikolaeva NN, Nikolaeva LV, Gigileva NL (2005) Opisthorchiasis (epidemiology, clinical picture, diagnostics, medical treatment). Vrach 7:17–20 (in Russian)

    Google Scholar 

  20. 20.

    Ramirez B, Bickle Q, Yousif F, Fakorede F, Mouries MA, Nwaka S (2007) Schistosomes: challenges in compound screening. Expert Opin Drug Discov. https://doi.org/10.1517/17460441.2.S1.S53

    Article  PubMed  Google Scholar 

  21. 21.

    Sayasone S, Meister I, Andrews JR, Odermatt P, Vonghachack Y, Xayavong S, Senggnam K, Phongluxa K, Hattendorf J, Bogoch II, Keiser J (2017) Efficacy and safety of praziquantel against light infections of Opisthorchis viverrini: a randomized parallel single-blind dose-ranging trial. Clin Infect Dis 64(4):451–458. https://doi.org/10.1093/cid/ciw785

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Sereerak P, Upontain S, Tangkawattana P, Mallory FF, Sripa B, Tangkawattana S (2017) Efficacious and safe dose of praziquantel for the successful treatment of feline reservoir hosts with opisthorchiasis. Parasitol Int 66(4):448–452. https://doi.org/10.1016/j.parint.2016.08.005

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Sun Q, Mao R, Wang D, Hu C, Zheng Y, Sun D (2016) The cytotoxicity study of praziquantel enantiomers. Drug Des Devel Ther 10:2061–2068. https://doi.org/10.2147/DDDT.S98096

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Suwannatrai A, Saichua P, Haswell M (2018) Epidemiology of Opisthorchis viverrini Infection. Adv Parasitol 101:41–67. https://doi.org/10.1016/bs.apar.2018.05.002.29

    Article  PubMed  Google Scholar 

  25. 25.

    Udilov VS, Borzunov VM, Soldatov DA (2013) Estimation of effectiveness antiparasitic therapy in superinvasion of Opisthorchis felineus. Popul Health Habitat 9(246):40–42 (in Russian)

    Google Scholar 

  26. 26.

    Wang ZX, Chen JL, Qiao C (2013) Praziquantel derivatives with antischistosomal activity: aromatic ring modification. Chem Biol Drug Des 82(2):216–225. https://doi.org/10.1111/cbdd.12153

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Wangboon C, Worasith C, Thanan R, Eamudomkarn C, Techasen A, Sithithaworn J, Loilome W, Chamadol N, Pinlaor S, Jumnainsong A, Yongvanit P, Khuntikeo N, Bethony JM, Sithithaworn P (2019) Evaluation of a short term effect of praziquantel treatment in opisthorchiasis-induced hepatobiliary inflammation by urinary 8-oxodG. Acta Trop 189:124–128. https://doi.org/10.1016/j.actatropica.2018.10.003

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Xiao SH, Mei JY, Jiao PY (2009) The in vitro effect of mefloquine and praziquantel against juvenile and adult Schistosoma japonicum. Parasitol Res 106(1):237–246. https://doi.org/10.1007/s00436-009-1656-x

    Article  PubMed  Google Scholar 

Download references

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).

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Authors

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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Keywords

  • Opisthorchis felineus
  • Praziquantel
  • Disodium glycyrrhizinate
  • (R)-PZQ and (S)-PZQ