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.
Pharmaceutically active compounds are major contaminants of aquatic environments that show direct and indirect effects on aquatic organisms even at low concentrations. The aim of this study was to assess the effects of the illicit drug methamphetamine and the antidepressant sertraline on clonal marbled crayfish Procambarus virginalis. Crayfish exposed to the environmentally relevant concentrations of methamphetamine of ∼1 μg L-1 did not exhibit significant differences from unexposed controls in distance moved, velocity, and activity level with or without available shelter. Sertraline-exposed (∼1 μg L-1) crayfish were significantly more active, regardless of available shelter, and moved greater distances when shelter was available, compared to control crayfish. Crayfish exposed to methamphetamine and sertraline spent significantly more time outside the shelters compared to controls. Sertraline-exposed crayfish spawned more frequently and showed higher mortality than controls. The results suggest that the low environmental concentrations of the tested compounds could alter the behavior and life history traits of crayfish, resulting in higher reproductive effort and mortality.
- MeSH
- bezobratlí MeSH
- chemické látky znečišťující vodu toxicita MeSH
- chování zvířat účinky léků MeSH
- methamfetamin toxicita MeSH
- sertralin toxicita MeSH
- severní raci účinky léků růst a vývoj MeSH
- stadia vývoje účinky léků MeSH
- vodní organismy účinky léků růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
