Effects of supramolecular complexation of praziquantel with disodium glycyrrhizinate on the liver fluke Opisthorchis felineus: An in vitro and in vivo study

Effects of supramolecular complexation of praziquantel with disodium glycyrrhizinate on the liver fluke Opisthorchis felineus: An in vitro and in vivo study Full article

Journal

Acta Tropica
ISSN: 0001-706X , E-ISSN: 1873-6254

Output data

Year: 2019, Volume: 194, Pages: 1-12 Pages count : 12 DOI: 10.1016/j.actatropica.2019.03.017

Tags

Hamsters; Opisthorchis felineus; Praziquantel; Disodium glycyrrhizinate; Host physiological state

Authors

Avgustinovich Damira ¹ , Tsyganov Mikhail ¹ , Vishnivetskaya Galina ¹ , Kovner Anna ¹ , Sorokina Irina ² , Orlovskaya Irina ³ , Toporkova Lyudmila ³ , Goiman Elena ³ , Tolstikova Tatiana ² , Dushkin Alexander ^4,5 , Lyakhov Nikolay ⁴ , Mordvinov Viatcheslav ¹

Affiliations

1	(Данные Web of science) RAS, SB, Inst Cytol & Genet, Novosibirsk, Russia
2	(Данные Web of science) RAS, SB, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk, Russia
3	(Данные Web of science) Res Inst Fundamental & Clin Immunol, Novosibirsk, Russia
4	(Данные Web of science) RAS, SB, Inst Solid State Chem & Mechanochem, Novosibirsk, Russia
5	(Данные Web of science) Zhejiang Univ Technol, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Natl Engn Res Ctr Proc Dev Act Pharmaceut Ingredi, Hangzhou, Zhejiang, Peoples R China

Millions of people worldwide have a chronic infection with the liver fluke Opisthorchis felineus, which causes opisthorchiasis in humans and animals. The only known effective drug for this disease is praziquantel (PrzQ); however, its efficacy is below 100%, and it has some adverse effects. In this study, a water-soluble complex of PrzQ with a disodium salt of glycyrrhizic acid (disodium glycyrrhizinate; Na(2)GA) in a 1:10 ratio (PrzQ:GA) allowed the PrzQ dose to be decreased 11-fold for effective killing of O. felineus. An in vitro experiment showed a sufficient anthelmintic efficiency of PrzQ:GA against both adult and juvenile O. felineus individuals. A Syrian golden hamster model of opisthorchiasis revealed a considerable anthelmintic effect at all tested PrzQ:GA doses (50, 100, 200, 400, and 1100 mg/kg) with the best performance at 400 and 1100 mg/kg. Further comparison of the effects of PrzQ (400 mg/kg) and PrzQ:GA (400 mg/kg) regarding the state of the host indicated significant advantages of the latter. Histological examination showed that PrzQ:GA was better at decreasing the O. felineus-induced inflammatory infiltration (as compared with PrzQ alone) as well as interfered with the development of epithelial dysplasia and metaplasia in large bile ducts and cholangiofibrosis. Both PrzQ and PrzQ:GA decreased the number of myeloid (CFU-GM) and erythroid (BFU-E + CFU-E) colonies induced by O. felineus infection. The drugs had no negative effect on the animal behavior in an open field test 2-4 h after administration. Thus, PrzQ:GA proved to be a good anthelmintic agent having no evident adverse effects on the host, thereby suggesting that further preclinical and clinical trials would be warranted.

Avgustinovich D. , Tsyganov M. , Vishnivetskaya G. , Kovner A. , Sorokina I. , Orlovskaya I. , Toporkova L. , Goiman E. , Tolstikova T. , Dushkin A. , Lyakhov N. , Mordvinov V.
Effects of supramolecular complexation of praziquantel with disodium glycyrrhizinate on the liver fluke Opisthorchis felineus: An in vitro and in vivo study
Acta Tropica. 2019. V.194. P.1-12. DOI: 10.1016/j.actatropica.2019.03.017 WOS Scopus РИНЦ OpenAlex

Published print:

Jun 1, 2019

Web of science:	WOS:000467666100001
Scopus:	2-s2.0-85062972437
Elibrary:	38703926
OpenAlex:	W2922075377

DB	Citing
Web of science	9
Scopus	6
Elibrary	14
OpenAlex	8