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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References
Alsaqabi SM, Lofty WM (2014) Praziquantel: a review. J Veterinar Sci Technol 5:5. https://doi.org/10.4172/2157-7579.1000200
Avgustinovich DF, Tsyganov MA, Pakharukova MYu, Chulakov EN, Dushkin AV, Krasnov VP, Mordvinov VA (2020) Effectiveness of repeated administration of praziquantel with disodium glycyrrhizinate and two enantiomers of praziquantel on Opisthorchis felineus (Rivolta, 1884). Acta Parasitologica 65:156–164. https://doi.org/10.2478/s11686-019-00149-2
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
Ayé P, Phongluxa K, Vonghachack Y, Sayasone S, Oroth R, Odermatt P (2020) Patients with severe schistosomiasis mekongi morbidity demonstrating ongoing transmission in Southern Lao People’s Democratic Republic. Acta Trop. https://doi.org/10.1016/j.actatropica.2019.105323
Baykova OA, Nikolaeva NN, Grishchenko EG, Nikolaeva LV (2017) Opisthorchiasis and clonorchiasis treatment: modern approach, concerns and perspectives. The Journal of scientific articles “Health and Education Millennium” 19(6):14‒25. http://www.clinical-journal.co.uk/gallery/print_2017_6.pdf#page=14 (in Russian)
Boonmars T, Srirach P, Kaewsamut B, Srisawangwong T, Pinlaor S, Pinlaor P, Yongvanit P, Sithithaworn P (2008) Apoptosis-related gene expression in hamster opisthorchiasis post praziquantel treatment. Parasitol Res 102(3):447–455. https://doi.org/10.1007/s00436-007-0783-5
Boonmars T, Srisawangwong T, Srirach P, Kaewsamut B, Pinlaor S, Sithithaworn P (2007) Apoptosis-related gene expressions in hamsters re-infected with Opisthorchis viverrini and re-treated with praziquantel. Parasitol Res 102(1):57–62. https://doi.org/10.1007/s00436-007-0724-3
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 drugpraziquantel and interactions with calcium carbonate. Eur J Pharm Biopharm 132:180–191. https://doi.org/10.1016/j.ejpb.2018.09.028
Cavalcanti DM, Lotufo CM, Borelli P, Ferreira ZS, Markus RP, Farsky SH (2007) Endogenous glucocorticoids control neutrophil mobilization from bone marrow to blood and tissues in non-inflammatory conditions. Br J Pharmacol 152(8):1291–1300. https://doi.org/10.1038/sj.bjp.0707512
Cavalcanti DM, Lotufo CM, Borelli P, Tavassi AM, Pereira AL, Markus RP, Farsky SH (2006) Adrenal deficiency alters mechanisms of neutrophil mobilization. Mol Cell Endocrinol 249(1–2):32–39. https://doi.org/10.1016/j.mce.2006.01.007
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
Charoensuk L, Pinlaor P, Wanichwecharungruang S, Intuyod K, Vaeteewoottacharn K, Chaidee A, Yongvanit P, Pairojkul C, Suwannateep N, Pinlaor S (2016) Nanoencapsulated curcumin and praziquantel treatment reduces periductal fibrosis and attenuates bile canalicular abnormalities in Opisthorchis viverrini-infected hamsters. Nanomedicine 12(1):21–32. https://doi.org/10.1016/j.nano.2015.10.005
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, NJ, USA
Dushkin AV, Tolstikova TG, Khvostov MV, Tolstikov GA (2012) Complexes of polysaccharides and glycyrrhizic acid with drug molecules. Mechanochemical synthesis and pharmacological activity. In: Karunaratne DN (ed) The Complex World of Polysaccharides. Croatia, InTech, pp 573–602. https://doi.org/10.5772/48182
Hanpanich P, Laha T, Sripa B, Mairiang E, Sereerak P, Upontain S, Tangkawattana P, Brindley PJ, Tangkawattana S (2017) Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model. Parasitol Int 66(4):464–470. https://doi.org/10.1016/j.parint.2016.04.012
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
Kamsa-Ard S, Luvira V, Pugkhem A, Luvira V, Thinkhamrop B, Suwanrungruang K, Bhudhisawasdi V (2015) Association between praziquantel treatment and cholangiocarcinoma: a hospital-based matched case-control study. BMC Cancer 15:776. https://doi.org/10.1186/s12885-015-1788-6
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
Kim AV, Shelepova EA, Selyutina OY, Meteleva ES, Dushkin AV, Medvedev NN, Polyakov NE, Lyakhov NZ (2019) Glycyrrhizin-assisted transport of praziquantel anthelmintic drug through the lipid membrane: an experiment and MD simulation. Mol Pharm 16(7):3188–3198. https://doi.org/10.1021/acs.molpharmaceut.9b00390
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
Kyung SY, Cho YK, Kim YJ, Park JW, Jeong SH, Lee JI, Sung YM, Lee SP (2011) A paragonimiasis patient with allergic reaction to praziquantel and resistance to triclabendazole: successful treatment after desensitization to praziquantel. Korean J Parasitol 49(1):73–77. https://doi.org/10.3347/kjp.2011.49.1.73
Litvinova LS, Riazantseva NV, Novitskiĭ VV (2008) Dysregulation of cooperative interactions of immunocytes and eosinophils in the mechanism of development of eosinophilia in Opisthorhis felineus invasion. Med Parazitol (Mosk) 3(3):13–17 (in Russian)
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
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
Midzi N, Sangweme D, Zinyowera S, Mapingure MP, Brouwer KC, Kumar N, Mutapi F, Woelk G, Mduluza T (2008) Efficacy and side effects of praziquantel treatment against Schistosoma haematobium infection among primary school children in Zimbabwe. Trans R Soc Trop Med Hyg 102(8):759–766. https://doi.org/10.1016/j.trstmh.2008.03.010
Nikolaeva NN, Nikolaeva LV, Gigileva NL (2005) Opisthorchiasis (epidemiology, clinical picture, diagnostics, medical treatment). Vrach 7:17–20. https://elibrary.ru/download/elibrary_15104723_64259774.pdf (in Russian)
Pakharukova MY, Shilov AG, Pirozhkova DS, Katokhin AV, Mordvinov VA (2015) The first comprehensive study of praziquantel effects in vivo and in vitro on European liver fluke Opisthorchis felineus (Trematoda). Int J Antimicrob Agents 46:94–100. https://doi.org/10.1016/j.ijantimicag.2015.02.012
Pinlaor S, Prakobwong S, Boonmars T, Wongkham C, Pinlaor P, Hiraku Y (2009) Effect of praziquantel treatment on the expression of matrix metalloproteinases in relation to tissue resorption during fibrosis in hamsters with acute and chronic Opisthorchis viverrini infection. Acta Trop 111(2):181–191. https://doi.org/10.1016/j.actatropica.2009.04.011
Ramirez B, Bickle Q, Yousif F, Fakorede F, Mouries MA, Nwaka S (2007) Schistosomes: challenges in compound screening. Expert Opin Drug Discov 2(s1):S53-61. https://doi.org/10.1517/17460441.2.S1.S53
Tinga N, De N, Vien HV, Chau L, Toan ND, Kager PA, Vries PJ (1999) Little effect of praziquantel or artemisinin on clonorchiasis in Northern Vietnam. A pilot study. Trop Med Int Health 4(12):814–818. https://doi.org/10.1046/j.1365-3156.1999.00499.x
Udilov VS, Borzunov VM, Soldatov DA (2013) Estimation of effectiveness antiparasitic therapy in superinvasion Opisthorchis felineus. Zdorov’e naselenia i sreda obitania. 9:40‒42. https://elibrary.ru/download/elibrary_20321232_59675729.pdf (in Russian)
Vale N, Gouveia MJ, Rinaldi G, Brindley PJ, Gärtner F, Costa JMC (2017) Praziquantel for schistosomiasis: single-drug metabolism revisited, mode of action, and resistance. Antimicrob Agents Chemother 61:e02582-e2616. https://doi.org/10.1128/AAC.02582-16
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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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.
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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. 66, 623–630 (2021). https://doi.org/10.1007/s11686-020-00329-5
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DOI: https://doi.org/10.1007/s11686-020-00329-5