Shun Zhou,Liwei Xia,Jing Dong,Yongtao Liu,Qiuhong Yang,Ning Xu,Yibin Yang,Xiaohui Ai
Monogenean parasites pose a significant challenge to aquaculture, leading to adverse effects on fish health and yields. Current anthelmintic treatments for monogeneans have demonstrated limited efficacy and are further complicated by potential issues, which emphasize the necessity for effective and safe therapeutic strategies to manage monogeneans in aquaculture. In this study, in vivo and in vitro anthelmintic activity of febantel against Gyrodactylus kobayashii on goldfish ( Carassius auratus ), as well as its toxicity to goldfish were evaluated. In vivo assays indicated that febantel exhibited potent anthelmintic activity against G. kobayashii with an EC 50 value of 0.03 mg/L and 100 % anthelmintic efficacy at 0.1 mg/L after 48 h of exposure. Moreover, in vivo trials also revealed a notable post-treatment effect of febantel, where infected goldfish transferred to drug-free water after short 6-h exposure could still result in full eradication of the worms, indicating febantel might induce persistent perturbations in parasite physiology. In vitro assays showed a negative correlation between febantel concentrations and the survival of G. kobayashii . However, increasing the febantel concentration to 2.0 mg/L did not result in the complete death of all worms. Oral administration of febantel demonstrated limited anthelmintic activity, with only 49 % efficacy at a dosage of 200 mg/kg body weight daily over five days. Acute toxicity assays revealed the 48-h LC 50 value of febantel was 5.47 mg/L, which was 182.23 times higher than the 48-h EC 50 value, indicating that febantel has a favorable safety profile. However, febantel exposure potentially interfered with hepatic metabolism and oxidative status, as indicated by variations in SOD , GST , and P450 gene expression. In conclusion, treatment with 0.1 mg/L febantel for 24 h completely eradicated G. kobayashii infection on goldfish, demonstrating febantel’s potent anthelmintic activity. Coupled with its safety profile and extended post-treatment effectiveness, febantel is a promising candidate for controlling Gyrodactylus infections in aquaculture.
Monogeneans are ectoparasitic flatworms causing significant economic losses in aquaculture. This study aimed to identify potential anthelmintic agents against these parasites by integrating computer-aided drug design (CADD) and in vivo evaluation. The β-tubulin gene, a well-established anthelmintic target, was cloned from Gyrodactylus kobayashii and its three-dimensional structure was generated using homology modelling. Virtual screening of 2319 FDA-approved drugs and nine common benzimidazoles against the modelled β-tubulin identified several promising compounds with low binding energy. Subsequent in vivo anthelmintic efficacy and acute toxicity assays in goldfish revealed etravirine as a potent candidate with an EC 50 value of 0.55 mg/L and a therapeutic index (TI) greater than 18.18. This favourable safety profile highlights etravirine's potential for controlling monogenean infections in aquaculture. Flubendazole and mebendazole also demonstrated potent anthelmintic activity, with EC 50 values of 0.022 and 0.023 mg/L and therapeutic indices exceeding 45.45 and 43.48, respectively. Molecular dynamics simulations confirmed stable binding modes for flubendazole and mebendazole with β-tubulin, providing mechanistic insights into their anthelmintic activity. Overall, this study demonstrated the utility of CADD in identifying potential therapeutic agents against monogenean and underscored the importance of β-tubulin as a key target for anthelmintic therapy, contributing to the development of sustainable aquaculture practices.
Xiaoping Tan,Yang Hu,Shenye Qu,Gaoxue Wang,Tianqiang Liu
Noxious pathogens always lead to high rates of mortality, which results in severe economic losses in aquaculture. Currently, gyrodactylosis treatments mainly rely on unapproved chemicals, which are not always satisfactory. According to the previous study, arctigenin is an efficient natural product for controlling gyrodactylosis. For the sake of seeking high-efficiency compounds, a new arctigenin derivative (CCA) was synthesized. Next, we evaluated the anthelmintic activity of CCA in vitro and in vivo , and studied the mechanism of action. The number of Gyrodactylus kobayashii significantly reduced as compared with the control group, the EC 50 value at 24 and 48-h after CCA treatment was 0.616 and 0.451 mg/L, respectively, with EC 100 at CCA concentration of 3 mg/L after 1 h bath treatment. In vitro results showed that CCA can rapidly reduce the amount of G. kobayashii and inhibit its mobility that could normally lead to death. The concentration and duration of CCA were positively correlated with the mortality of G. kobayashii . In addition, CCA displayed 100% efficacy against G. kobayashii at 4.0 mg/L after only 20 min exposure. Acute toxicity assay demonstrated that the LC 50 of CCA against goldfish was 5.012 mg/L, which was 8.13 times higher than that of the EC 50 . Furthermore, the results of confocal microscope study revealed that CCA leaded to the epidermal structure and dissolved muscles of worms. Moreover, the ATP level of worms were decreased sharply after both in vitro and in vivo exposures with CCA. The anthelminthic mechanism of CCA against gyrodactylids was related to epidermal structure damages and energy insufficient. From the previous study, the EC 50 of CCA against G. kobayashii (0.616 mg/L) was much lower than the EC 50 (1.85 mg/L) of arctigenin ( Tu et al., 2018 ). In summary, CCA is more effective than arctigenin and has great potential in control of Gyrodactylus infections.
危险品化学品经营许可证（带存储）