TY - JOUR

T1 - A study of tribendimidine effects in vitro and in vivo on the liver fluke Opisthorchis felineus

AU - Pakharukova, Maria Y.

AU - Samsonov, Vladimir A.

AU - Serbina, Elena A.

AU - Mordvinov, Viatcheslav A.

N1 - Publisher Copyright: © 2019 The Author(s).

PY - 2019/1/11

Y1 - 2019/1/11

N2 - Background: The food-borne liver fluke Opisthorchis felineus is an epidemiologically important species and the causative agent of opisthorchiasis across an extensive territory of Eurasia. For decades, treatment of opisthorchiasis has been based on praziquantel. Tribendimidine could be an alternative drug that has been successfully tested for Opisthorchis viverrini and Clonorchis sinensis infections. We aimed to assess tribendimidine effects in comparison with praziquantel in vivo and in vitro against the liver fluke Opisthorchis felineus. Results: In this study we (i) calculated half-maximal inhibitory concentrations (IC50) by motility tests against O. felineus adults and newly excysted metacercarie after tribendimidine treatment in vitro; (ii) determined whether tribendimidine and PZQ effects on adult liver flukes are dependent on or mediated by white blood cells; and (iii) tested in vivo the anthelmintic activity of tribendimidine on juvenile and adult worms. We found that the efficiency of tribendimidine in vitro was similar (IC50 = 0.23 μM for newly excysted metacercariae and 0.19 μM for adult worms) to that of praziquantel (IC50 0.98 μM for newly excysted metacercariae and 0.47 μM for adult worms). The treatment of adult worms in vivo with praziquantel or tribendimidine at 400 mg/kg resulted in a 76% and 77.2% reduction, respectively, in the worm burden during chronic infection. Conclusions: The differences between WBR values after PZQ and TBN treatment were not significant, thus tribendimidine was as effective as praziquantel against O. felineus liver flukes. Given the broad-spectrum activity of tribendimidine and efficacy against O. felineus, this drug may be a promising candidate for the treatment of opisthorchiasis felinea and other liver fluke infections.

AB - Background: The food-borne liver fluke Opisthorchis felineus is an epidemiologically important species and the causative agent of opisthorchiasis across an extensive territory of Eurasia. For decades, treatment of opisthorchiasis has been based on praziquantel. Tribendimidine could be an alternative drug that has been successfully tested for Opisthorchis viverrini and Clonorchis sinensis infections. We aimed to assess tribendimidine effects in comparison with praziquantel in vivo and in vitro against the liver fluke Opisthorchis felineus. Results: In this study we (i) calculated half-maximal inhibitory concentrations (IC50) by motility tests against O. felineus adults and newly excysted metacercarie after tribendimidine treatment in vitro; (ii) determined whether tribendimidine and PZQ effects on adult liver flukes are dependent on or mediated by white blood cells; and (iii) tested in vivo the anthelmintic activity of tribendimidine on juvenile and adult worms. We found that the efficiency of tribendimidine in vitro was similar (IC50 = 0.23 μM for newly excysted metacercariae and 0.19 μM for adult worms) to that of praziquantel (IC50 0.98 μM for newly excysted metacercariae and 0.47 μM for adult worms). The treatment of adult worms in vivo with praziquantel or tribendimidine at 400 mg/kg resulted in a 76% and 77.2% reduction, respectively, in the worm burden during chronic infection. Conclusions: The differences between WBR values after PZQ and TBN treatment were not significant, thus tribendimidine was as effective as praziquantel against O. felineus liver flukes. Given the broad-spectrum activity of tribendimidine and efficacy against O. felineus, this drug may be a promising candidate for the treatment of opisthorchiasis felinea and other liver fluke infections.

KW - Food-borne trematodes

KW - Hamster model

KW - in vitro

KW - in vivo

KW - Opisthorchis felineus

KW - Tribendimidine

KW - Praziquantel/pharmacology

KW - Cricetinae

KW - Phenylenediamines/pharmacology

KW - Animals

KW - Anthelmintics/pharmacology

KW - Opisthorchis/drug effects

KW - Mesocricetus

KW - Opisthorchiasis/drug therapy

KW - ARTEMETHER

KW - EFFICACY

KW - SAFETY

KW - SCHISTOSOMA-MANSONI

KW - CLONORCHIS-SINENSIS

KW - PRAZIQUANTEL

KW - VIVERRINI

KW - TEGUMENT

KW - INFECTION

UR - http://www.scopus.com/inward/record.url?scp=85059868562&partnerID=8YFLogxK

U2 - 10.1186/s13071-019-3288-z

DO - 10.1186/s13071-019-3288-z

M3 - Article

C2 - 30635027

AN - SCOPUS:85059868562

VL - 12

SP - 23

JO - Parasites and Vectors

JF - Parasites and Vectors

SN - 1756-3305

IS - 1

M1 - 23

ER -