Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm <i>Moniezia expansa</i>

Prchal, Lukáš; Bártíková, Hana; Bečanová, Aneta; Jirásko, Robert; Vokřál, Ivan; Stuchlíková, Lucie Raisová; Skálová, Lenka; Kubı́ček, Vladimı́r; Lamka, J.; Trejtnar, František; Szotáková, Barbora

doi:10.1017/s0031182014001711

Cited by 12 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of SDRs in anthelmintic resistance is not well known. However, in several helminths, SDR genes have been shown to be involved in metabolic activities of BZs [73][74][75][76][77]. Even though we did not observe any major expressional response of SDR genes in C. elegans after IVM exposure, an increase in expression of dhs-23 in a BZ-resistant strain of C. elegans after in vitro exposure to BZ derivatives has been reported [35].…”

Section: Discussioncontrasting

confidence: 60%

Ivermectin-induced gene expression changes in adult Parascaris univalens and Caenorhabditis elegans: a comparative approach to study anthelminthic metabolism and resistance in vitro

et al. 2022

View full text Add to dashboard Cite

Background The nematode Parascaris univalens is one of the most prevalent parasitic pathogens infecting horses but anthelmintic resistance undermines treatment approaches. The molecular mechanisms underlying drug activity and resistance remain poorly understood in this parasite since experimental in vitro models are lacking. The aim of this study was to evaluate the use of Caenorhabditis elegans as a model for P. univalens drug metabolism/resistance studies by a comparative gene expression approach after in vitro exposure to the anthelmintic drug ivermectin (IVM). Methods Twelve adult P. univalens worms in groups of three were exposed to ivermectin (IVM, 10–13 M, 10–11 M, 10–9 M) or left unexposed for 24 h at 37 °C, and total RNA, extracted from the anterior end of the worms, was sequenced using Illumina NovaSeq. Differentially expressed genes (DEGs) involved in metabolism, transportation, or gene expression with annotated Caernorhabditis elegans orthologues were identified as candidate genes to be involved in IVM metabolism/resistance. Similarly, groups of 300 adult C. elegans worms were exposed to IVM (10–9 M, 10–8 M and 10–7 M) or left unexposed for 4 h at 20 °C. Quantitative RT-PCR of RNA extracted from the C. elegans worm pools was used to compare against the expression of selected P. univalens candidate genes after drug treatment. Results After IVM exposure, 1085 DEGs were found in adult P. univalens worms but the relative gene expression changes were small and large variabilities were found between different worms. Fifteen of the DEGs were chosen for further characterization in C. elegans after comparative bioinformatics analyses. Candidate genes, including the putative drug target lgc-37, responded to IVM in P. univalens, but marginal to no responses were observed in C. elegans despite dose-dependent behavioral effects observed in C. elegans after IVM exposure. Thus, the overlap in IVM-induced gene expression in this small set of genes was minor in adult worms of the two nematode species. Conclusion This is the first time to our knowledge that a comparative gene expression approach has evaluated C. elegans as a model to understand IVM metabolism/resistance in P. univalens. Genes in P. univalens adults that responded to IVM treatment were identified. However, identifying conserved genes in P. univalens and C. elegans involved in IVM metabolism/resistance by comparing gene expression of candidate genes proved challenging. The approach appears promising but was limited by the number of genes studied (n = 15). Future studies comparing a larger number of genes between the two species may result in identification of additional candidate genes involved in drug metabolism and/or resistance. Graphical Abstract

show abstract

Section: Discussioncontrasting

confidence: 60%

Ivermectin-induced gene expression changes in adult Parascaris univalens and Caenorhabditis elegans: a comparative approach to study anthelminthic metabolism and resistance in vitro

et al. 2022

View full text Add to dashboard Cite

show abstract

“…F. hepatica metabolizes triclabendazole (TCBZ) into sulfoxide (TCBZ-SO) and sulphone (TCBZ-SO2), these metabolized products were found at higher concentrations in resistance strains (Solana et al, 2001; Mottier et al, 2004; Robinson et al, 2004). The cestode, Moniezia expansa , biotransforms flubendazole and mebendazole by reduction and albendazole was oxidized to albendazole sulfone and sulfoxide (Prchal et al, 2015). The parasitic nematodes, Ascaris suum and Haemonchus contortus , have also been shown to biotransform several benzimidazoles.…”

Section: Introductionmentioning

confidence: 99%

Similarities and differences in the biotransformation and transcriptomic responses of Caenorhabditis elegans and Haemonchus contortus to five different benzimidazole drugs

Stasiuk

MacNevin

Workentine

et al. 2019

International Journal for Parasitology: Drugs and Drug Resistan

View full text Add to dashboard Cite

We have undertaken a detailed analysis of the biotransformation of five of the most therapeutically important benzimidazole anthelmintics - albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) - in Caenorhabditis elegans and the ruminant parasite Haemonchus contortus. Drug metabolites were detected by LC-MS/MS analysis in supernatants of C. elegans cultures with a hexose conjugate, most likely glucose, dominating for all five drugs. This work adds to a growing body of evidence that glucose conjugation is a major pathway of xenobiotic metabolism in nematodes and may be a target for enhancement of anthelmintic potency. Consistent with this, we found that biotransformation of albendazole by C. elegans reduced drug potency. Glucose metabolite production by C. elegans was reduced in the presence of the pharmacological inhibitor chrysin suggesting that UDP-glucuronosyl/glucosyl transferase (UGT) enzymes may catalyze benzimidazole glucosidation. Similar glucoside metabolites were detected following ex vivo culture of adult Haemonchus contortus. As a step towards identifying nematode enzymes potentially responsible for benzimidazole biotransformation, we characterised the transcriptomic response to each of the benzimidazole drugs using the C. elegans resistant strain CB3474 ben-1(e1880)III. In the case of albendazole, mebendazole, thiabendazole, and oxfendazole the shared transcriptomic response was dominated by the up-regulation of classical xenobiotic response genes including a shared group of UGT enzymes (ugt-14/25/33/34/37/41/8/9). In the case of fenbendazole, a much greater number of genes were up-regulated, as well as developmental and brood size effects suggesting the presence of secondary drug targets in addition to BEN-1. The transcriptional xenobiotic response of a multiply resistant H. contortus strain UGA/2004 was essentially undetectable in the adult stage but present in the L3 infective stage, albeit more muted than C. elegans. This suggests that xenobiotic responses may be less efficient in stages of parasitic nematodes that reside in the host compared with the free-living stages.

show abstract

“…The Moniezia spp. were common parasites which affect ruminants, including sheep, cattle and other species (Prchal et al, 2015). Moniezia expansa was considered as the most important cestode parasites infected sheep (Hassanain et al, 2014), whereas M. benedeni was more common in cattle.…”

Section: Discussionmentioning

confidence: 99%

Morphological identification and phylogenetic analysis of Moniezia species isolated from sheep in Wasit province/ Iraq

Sray

Faraj

2022

ijhs

View full text Add to dashboard Cite

The current study was conducted during the period from December 2020 to August 2021 for detect the infection of Moniezia parasite in sheep using the traditional and molecular diagnostic methods as well as for confirmation of Moniezia species in sheep by the phylogenetic analysis. The samples fresh adult worms Moniezia were collected from intestines of sheep the locations of samples were obtained from abattoirs in Wasit province and also regarding months, sexes and ages affecting on infection prevalence rate. Results of microscopically, the samples fresh adult worms Moniezia spp. were collected from intestines of 125 sheep and stained with semichon's acid carmine and examined by light microscope, the results were revealed on 29 (23.2%) positive. Concerning to Moniezia spp. have been identified and classified out of 29 from sheep showed that M. expansa and M. benedeni 26 (89.65%) and 3(10.34%) respectively, with a significant difference (P≤0.01). Regarding to risk factors (sex, age and months), significant (P≤0.01) increase in sheep Monieziasis was reported in age groups <1year (37.5%) more than 1-2 year (14.28%) and > 2year (7.40%). No significant difference was observed in infection rates between male and female.

show abstract

Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa

Cited by 12 publications

References 50 publications

Ivermectin-induced gene expression changes in adult Parascaris univalens and Caenorhabditis elegans: a comparative approach to study anthelminthic metabolism and resistance in vitro

Ivermectin-induced gene expression changes in adult Parascaris univalens and Caenorhabditis elegans: a comparative approach to study anthelminthic metabolism and resistance in vitro

Similarities and differences in the biotransformation and transcriptomic responses of Caenorhabditis elegans and Haemonchus contortus to five different benzimidazole drugs

Morphological identification and phylogenetic analysis of Moniezia species isolated from sheep in Wasit province/ Iraq

Contact Info

Product

Resources

About