In all organisms, the biotransformation of xenobiotics to less toxic and more hydrophilic compounds represents an effective defense strategy. In pathogens, the biotransformation of drugs (used for their elimination from the host) may provide undesirable protective effects that could potentially compromise the drug's efficacy. Accordingly, increased drug deactivation via accelerated biotransformation is now considered as one of the mechanisms of drug resistance. The present study summarizes the current knowledge regarding the biotransformation of anthelmintics, specifically drugs used to treat mainly nematodes, a group of parasites that are a significant health concern for humans and animals. The main biotransformation enzymes are introduced and their roles in anthelmintics metabolism in nematodes are discussed with a particular focus on their potential participation in drug resistance. Similarly, the inducibility of biotransformation enzymes with sublethal doses of anthelmintics is presented in view of its potential contribution to drug resistance development. In the conclusion, the main tasks awaiting scientists in this area are outlined.

• MeSH
• anthelmintika * farmakologie   metabolismus   farmakokinetika   MeSH
• biotransformace MeSH
• hlístice * účinky léků   metabolismus   enzymologie   MeSH
• léková rezistence * MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• anthelmintika * MeSH

Haemonchus contortus (family Trichostrongylidae, Nematoda), a hematophagous gastrointestinal parasite found in small ruminants, has a great ability to develop resistance to anthelmintic drugs. We studied the biotransformation of the three benzimidazole anthelmintics: albendazole (ABZ), ricobendazole (albendazole S-oxide; RCB) and flubendazole (FLU) in females and males of H. contortus in both a susceptible ISE strain and resistant IRE strain. The ex vivo cultivation of living nematodes in culture medium with or without the anthelmintics was used. Ultrasensitive UHPLC/MS/MS analysis revealed 9, 7 and 12 metabolites of ABZ, RCB and FLU, respectively, with most of these metabolites now described in the present study for the first time in H. contortus. The structure of certain metabolites shows the presence of biotransformation reactions not previously reported in nematodes. There were significant qualitative and semi-quantitative differences in the metabolites formed by male and female worms. In most cases, females metabolized drugs more extensively than males. Adults of the IRE strain were able to form many more metabolites of all the drugs than adults of the ISE strain. Some metabolites were even found only in adults of the IRE strain. These findings suggest that increased drug metabolism may play a role in resistance to benzimidazole drugs in H. contortus.

• Klíčová slova
• Anthelmintics, Benzimidazole, Drug metabolism, Drug resistance, Nematode,
• MeSH
• albendazol analogy a deriváty   metabolismus   farmakologie   MeSH
• anthelmintika metabolismus   farmakologie   MeSH
• biochemické jevy MeSH
• biotransformace MeSH
• Haemonchus metabolismus   MeSH
• hemonchóza farmakoterapie   parazitologie   veterinární   MeSH
• léková rezistence * MeSH
• mebendazol analogy a deriváty   metabolismus   farmakologie   MeSH
• nemoci ovcí farmakoterapie   parazitologie   MeSH
• ovce parazitologie   MeSH
• sexuální faktory MeSH
• tandemová hmotnostní spektrometrie MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• albendazol MeSH
• albendazole sulfoxide MeSH Prohlížeč
• anthelmintika MeSH
• flubendazole MeSH Prohlížeč
• mebendazol MeSH