gional Innovation DP Inhibitor review method (RIS)” through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (2021RIS-001). This research was also supported by the basic Science Study System by way of the National Investigation Foundation of Korea funded by the Ministry of Education (2019R1F1A1059173). Institutional Assessment Board Statement: Not applicable. Cathepsin L Inhibitor supplier Informed Consent Statement: Not applicable. Information Availability Statement: Information is contained within the article. Conflicts of Interest: The authors declare no conflict of interest.
(2021) 52:143 Zaj kovet al. Veterinary Research doi.org/10.1186/s13567-021-01012-xRESEARCH ARTICLEOpen AccessSertraline as a new possible anthelmintic against Haemonchus contortus: toxicity, efficacy, and biotransformationMark a Zaj kov, Luk Prchal2, Martina Navr ilov, Nikola Vodv kov, Petra Matouskov, Ivan Vok three, Linh Thuy Nguyen1 and Lenka Sk ovAbstract Haemonchus contortus is often a parasitic nematode of ruminants which causes substantial losses to many farmers worldwide. Since the drugs at present 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 very needed. As the antipsychotic drug sertraline (SRT) has been shown to be productive against the parasitic nematodes Trichuris muris, Ancylostoma caninum and Schistosoma mansoni, the aim from the present study was to evaluate the doable impact of SRT on H. contortus. The potential hepatotoxicity of SRT was tested in sheep, a popular H. contortus host. Additionally, the principle metabolic pathways of SRT in H. contortus and the ovine liver had been identified. While no effect of SRT on H. contortus egg hatching was observed, SRT was found to considerably reduce the viability of H. contortus adults in drug-sensitive and resistant strains, with its impact comparable to the normally utilised anthelmintics levamisole and monepantel. In addition, SRT in anthelmintically active concentrations showed no toxicity for the ovine liver. Biotransformation of SRT in H. contortus was weak, with most of the drug remaining unmetabolized. Production in the key metabolite hydroxy-SRT didn’t differ substantially between strains. Other minor metabolites such as SRT-O-glucoside, dihydroxy-SRT, and SRT-ketone had been also identified in H. contorts adults. In comparison with H. contortus, the ovine liver metabolized SRT much more extensively, mostly by means of desmethylation and glucuronidation. In conclusion, the potency of SRT against H. contortus was established, and it really should be tested further toward attainable repurposing. Keywords and phrases: Drug repurposing, drug metabolism, hepatotoxicity, drug resistance, nematodes Introduction Given that illnesses caused by parasitic nematodes are accompanied by numerous kinds of clinical complications, the continual and regular control of nematodes infection in livestock is essential for effective and welfare-friendly production. Pharmacotherapy of animals represents the fundamental method for the remedy of nematodiasis. Four major classes of prevalent anthelmintics are routinelyCorrespondence: [email protected] 1 Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovsk o 1203, 500 05 Hradec Kr ov Czech Republic Full list of author facts is obtainable at the finish on the articleadministered to livestock: benzimidazoles (e.g. mebendazole, albendazole, fenbendazole, flubendazole), imidazothiazoles (levamisole), macrocyclic lactones (ivermectin, moxidectin), and
