ArticleAntimicrobial agents and chemotherapy2014
Phenobarbital induction and chemical synergism demonstrate the role of UDP-glucuronosyltransferases in detoxification of naphthalophos by Haemonchus contortus larvae.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 24 citations in OpenAlex.
- In vitro analysis of the activities of commercial anthelmintics in the presence of inhibitors of xenobiotic detoxification pathways in Haemonchus contortus exsheathed L3 stage.Parasitology research · 2025Article
- Xenobiotic-Metabolizing Enzymes in Trematodes.Biomedicines · 2022Review
- Selection of Genome-Wide SNPs for Pooled Allelotyping Assays Useful for Population Monitoring.Genome biology and evolution · 2022Article
- Functional analysis of UGT201D3 associated with abamectin resistance in Tetranychus cinnabarinus (Boisduval).Insect science · 2020Article
- Similarities and differences in the biotransformation and transcriptomic responses of Caenorhabditis elegans and Haemonchus contortus to five different benzimidazole drugs.International journal for parasitology. Drugs and drug resistance · 2019Article
- Intestinal UDP-glucuronosyltransferase as a potential target for the treatment and prevention of lymphatic filariasis.PLoS neglected tropical diseases · 2019Article
- UDP-glycosyltransferase family in Haemonchus contortus: Phylogenetic analysis, constitutive expression, sex-differences and resistance-related differences.International journal for parasitology. Drugs and drug resistance · 2018Article
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3 authors at 1 institution in 1 country.
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Abstract
We used an enzyme induction approach to study the role of detoxification enzymes in the interaction of the anthelmintic compound naphthalophos with Haemonchus contortus larvae. Larvae were treated with the barbiturate phenobarbital, which is known to induce the activity of a number of detoxification enzymes in mammals and insects, including cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UDPGTs), and glutathione (GSH) S-transferases (GSTs). Cotreatment of larvae with phenobarbital and naphthalophos resulted in a significant increase in the naphthalophos 50% inhibitory concentration (IC50) compared to treatment of larvae with the anthelmintic alone (up to a 28-fold increase). The phenobarbital-induced drug tolerance was reversed by cotreatment with the UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, probenecid, and sulfinpyrazone. Isobologram analysis of the interaction of 5-nitrouracil with naphthalophos in phenobarbital-treated larvae clearly showed the presence of strong synergism. The UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, and probenecid also showed synergistic effects with non-phenobarbital-treated worms (synergism ratio up to 3.2-fold). This study indicates that H. contortus larvae possess one or more UDPGT enzymes able to detoxify naphthalophos. In highlighting the protective role of this enzyme group, this study reveals the potential for UDPGT enzymes to act as a resistance mechanism that may develop under drug selection pressure in field isolates of this species. In addition, the data indicate the potential for a chemotherapeutic approach utilizing inhibitors of UDPGT enzymes as synergists to increase the activity of naphthalophos against parasitic worms and to combat detoxification-mediated drug resistance if it arises in the field.
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