Damira Avgustinovich1,2, Maria Lvova3, Galina Vishnivetskaya3, Mikhail Tsyganov3,4, Irina Orlovskaya5, Lyudmila Toporkova5, Elena Goiman5, Aleksander Dushkin6,7, Nikolay Lyakhov6, Viatcheslav Mordvinov3. 1. Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russian Federation. avgust@bionet.nsc.ru. 2. Institute of Solid State Chemistry and Mechanochemistry (ISSCM), SB RAS, Kutateladze Str. 18, Novosibirsk, 630128, Russian Federation. avgust@bionet.nsc.ru. 3. Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russian Federation. 4. Novosibirsk State University, Pirogova Str. 10, Novosibirsk, 630090, Russian Federation. 5. Research Institute of Fundamental and Clinical Immunology, Siberian Branch of Russian Academy of Medical Sciences, Yadrintsevskaya Str. 14, Novosibirsk, 630099, Russian Federation. 6. Institute of Solid State Chemistry and Mechanochemistry (ISSCM), SB RAS, Kutateladze Str. 18, Novosibirsk, 630128, Russian Federation. 7. 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.
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.
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.
Entities:
Keywords:
Disodium glycyrrhizinate; Hamsters; In vitro; Opisthorchis felineus; Praziquantel
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