Biotransformation of flubendazole and selected model xenobiotics in Haemonchus contortus

Cvilink, V.; Kubı́ček, Vladimı́r; Nobilis, Milan; Křížová, Veronika; Szotáková, Barbora; Lamka, J.; Várady, Marián; Kuběnová, M.; Novotná, Romana; Gavelová, Martina; Skálová, Lenka

doi:10.1016/j.vetpar.2007.10.010

Cited by 22 publications

(27 citation statements)

References 21 publications

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“…Comparison of drug-metabolizing enzymes activities and biotransformation of anthelmintics in different helminths (M. expansa, H. diminuta, H. contortus, D. dendriticum) Enzyme/parent drug(Cvilink et al 2008a, b;Vokřál et al 2012Vokřál et al , 2013 results)(Cvilink et al 2009b;Bártíková et al 2010b; unpublished results) Cyt, cytosol-like fraction; Mic, microsomes-like fraction; Mit, mitochondria-like fraction; Ex, ex vivo; n.d., not detected;…”

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confidence: 99%

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

et al. 2014

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The sheep tapeworm Moniezia expansa is very common parasite, which affects ruminants such as sheep, goats as well as other species. The benzimidazole anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are often used to treat the infection. The drug-metabolizing enzymes of helminths may alter the potency of anthelmintic treatment. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of biotransformation enzymes were determined in subcellular fractions. Metabolites of the anthelmintics were detected and identified using high performance liquid chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were proved as well as activities of various metabolizing enzymes. Despite the fact that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl transferase and UDP-glucosyl transferase were active in vitro, no conjugated metabolites of anthelmintics were identified either ex vivo or in vitro. The obtained results indicate that sheep tapeworm is able to deactivate the administered anthelmintics, and thus protects itself against their action.

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confidence: 99%

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

et al. 2014

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“…[25,26] Alvinerie et al demonstrated the oxidative metabolism of moxidectin in H. contortus homogenate. [30][31][32] MOP was biotransformed via two-step sulfoxidation in H.contortus in contrary to ABZ with only one-step sulfoxidation. In the ex vivo study, H. contortus was not able to metabolize CLS and IVE.…”

Section: Discussionmentioning

confidence: 97%

Metabolic pathways of anthelmintic drug monepantel in sheep and in its parasite (Haemonchus contortus)

Stuchlíková

Jirásko

Vokřál

et al. 2014

Drug Testing and Analysis

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Monepantel (MOP) is a new anthelmintic drug intended for the treatment and control of gastrointestinal roundworms (nematodes) infection and associated disease in sheep. The aim of our study was to find out metabolic pathways of MOP in sheep in vivo and in its parasite Haemonchus contortus ex vivo. MOP biotransformation in two H. contortus strains with different sensitivity to anthelmintics was also compared. Ultra high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) technique is used for the identification of MOP metabolites in ovine urine, faeces, and nematodes. MOP biotransformation study in sheep in vivo led to the identification of 13 MOP metabolites; 7 of them have not been described previously in in vitro study. The study of MOP biotransformation in H. contorus ex vivo reveals four MOP metabolites. The nitrile hydrolysis as a new biotransformation pathway in helminths ex vivo is reported here for the first time. Unlike sheep, H. contorus nematodes are not able to metabolize MOP via phase II biotransformation. Nematodes of resistant White river (WR) strain form more types of MOP metabolites than nematodes of sensitive inbred susceptible Edinburgh (ISE) strain. Based on obtained results, schemes of metabolic pathways of MOP in sheep and nematodes are proposed.

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“…In this sense, some previous studies were addressed, particularly for BZ, to specify the enzymes involved, by identifying the metabolites formed by parasites. Under this approach, the ability of different helminth parasites to metabolize BZ was studied (Cvilink et al, 2008;Solana et al, 2001;Vokřál et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Development of novel valerolactam-benzimidazole hybrids anthelmintic derivatives: Diffusion and biotransformation studies in helminth parasites

Munguía

Michelena

Melian

et al. 2015

Experimental Parasitology

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Biotransformation of flubendazole and selected model xenobiotics in Haemonchus contortus

Cited by 22 publications

References 21 publications

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

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

Metabolic pathways of anthelmintic drug monepantel in sheep and in its parasite (Haemonchus contortus)

Development of novel valerolactam-benzimidazole hybrids anthelmintic derivatives: Diffusion and biotransformation studies in helminth parasites

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