Abstract
Haemonchus contortus is a parasitic nematode of ruminants which causes significant losses to many farmers worldwide. Since the drugs currently in use for the treatment of haemonchosis are losing their effectiveness due to the drug-resistance of this nematode, a new or repurposed drug is highly needed. As the antipsychotic drug sertraline (SRT) has been shown to be effective against the parasitic nematodes Trichuris muris, Ancylostoma caninum and Schistosoma mansoni, the aim of the present study was to evaluate the possible effect of SRT on H. contortus. The potential hepatotoxicity of SRT was tested in sheep, a common H. contortus host. In addition, the main metabolic pathways of SRT in H. contortus and the ovine liver were identified. While no effect of SRT on H. contortus egg hatching was observed, SRT was found to significantly decrease the viability of H. contortus adults in drug-sensitive and resistant strains, with its effect comparable to the commonly used anthelmintics levamisole and monepantel. Moreover, SRT in anthelmintically active concentrations showed no toxicity to the ovine liver. Biotransformation of SRT in H. contortus was weak, with most of the drug remaining unmetabolized. Production of the main metabolite hydroxy-SRT did not differ significantly between strains. Other minor metabolites such as SRT-O-glucoside, dihydroxy-SRT, and SRT-ketone were also identified in H. contorts adults. Compared to H. contortus, the ovine liver metabolized SRT more extensively, mainly via desmethylation and glucuronidation. In conclusion, the potency of SRT against H. contortus was proven, and it should be tested further toward possible repurposing.
Highlights
Since diseases caused by parasitic nematodes are accompanied by various types of clinical complications, the constant and regular control of nematodes infection in livestock is vital for efficient and welfare-friendly production
Effect of SRT on the viability of H. contortus adults The effect of SRT was tested separately in males and females of the inbred susceptible-Edinburgh strain (ISE) strain and IRE strain of H. contortus by measuring the adenosine triphosphate (ATP) level
The screening of drugs already approved for the treatment of other diseases and their review and possible repurposing for anthelmintic treatment represents an alternative to developing completely novel anthelmintic drugs
Summary
Since diseases caused by parasitic nematodes are accompanied by various types of clinical complications, the constant and regular control of nematodes infection in livestock is vital for efficient and welfare-friendly production. The effectiveness of the available anthelmintics over time has become limited due to increasing drug resistance in nematode populations [3]. Zajíčková et al Veterinary Research (2021) 52:143 recent anthelmintic in wide use, has occurred within less than four years of the product first being introduced is certainly disturbing [6, 7]. Considerable efforts have been devoted to the development of new anthelmintic drugs, especially those with more pronounced efficacy in nematodes resistant to classical anthelmintics [8]
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