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ArticleVeterinary research2024

Flubendazole carbonyl reduction in drug-susceptible and drug-resistant strains of the parasitic nematode Haemonchus contortus: changes during the life cycle and possible inhibition.

Nikola Rychlá, Martina Navrátilová, Eliška Kohoutová, Lucie Raisová Stuchlíková, Karolína Štěrbová, Josef Krátký, Petra Matoušková, Barbora Szotáková, Lenka Skálová

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Article in Veterinary research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
3.2field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Nikola RychláDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Martina NavrátilováDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Eliška KohoutováDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Lucie Raisová StuchlíkováDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Karolína ŠtěrbováDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Josef KrátkýDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Petra MatouškováDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Barbora SzotákováDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic.
Lenka SkálováDepartment of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského, 1203, Hradec Králové, Czech Republic. lenka.skalova@faf.cuni.cz.ORCID http://orcid.org/0000-0003-0741-3871
Charles University · CZ

Funding

Grantová Agentura České Republiky 20-14581YUniverzita Karlova v Praze GAUK 194421Univerzita Karlova v Praze SVV 260 664Univerzita Karlova v Praze UNCE/18/SCI/012
6 · The paper itself

Abstract

Carbonyl-reducing enzymes (CREs) catalyse the reduction of carbonyl groups in many eobiotic and xenobiotic compounds in all organisms, including helminths. Previous studies have shown the important roles of CREs in the deactivation of several anthelmintic drugs (e.g., flubendazole and mebendazole) in adults infected with the parasitic nematode Haemonchus contortus, in which the activity of a CRE is increased in drug-resistant strains. The aim of the present study was to compare the abilities of nematodes of both a drug-susceptible strain (ISE) and a drug-resistant strain (IRE) to reduce the carbonyl group of flubendazole (FLU) in different developmental stages (eggs, L1/2 larvae, L3 larvae, and adults). In addition, the effects of selected CRE inhibitors (e.g., glycyrrhetinic acid, naringenin, silybin, luteolin, glyceraldehyde, and menadione) on the reduction of FLU were evaluated in vitro and ex vivo in H. contortus adults. The results showed that FLU was reduced by H. contortus in all developmental stages, with adult IRE females being the most metabolically active. Larvae (L1/2 and L3) and adult females of the IRE strain reduced FLU more effectively than those of the ISE strain. Data from the in vitro inhibition study (performed with cytosolic-like fractions of H. contortus adult homogenate) revealed that glycyrrhetinic acid, naringenin, mebendazole and menadione are effective inhibitors of FLU reduction. Ex vivo study data showed that menadione inhibited FLU reduction and also decreased the viability of H. contortus adults to a similar extent. Naringenin and mebendazole were not toxic at the concentrations tested, but they did not inhibit the reduction of FLU in adult worms ex vivo.

Indexed as

AnthelminticsGlycyrrhetinic AcidHaemonchusAnimalsFemaleLarvaMebendazoleVitamin K 3AnthelminticsflubendazoleGlycyrrhetinic AcidMebendazoleVitamin K 3Anthelminticsdrug biotransformationhelminthsinhibitorsStrongyloides

Identifiers

PMID38225645
PMCPMC10790374
OpenAlexW4390886052

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.