Moxidectin toxicity to zebrafish embryos: Bioaccumulation and biomarker responses

Muniz, Marta Silva; Halbach, Katharina; Araruna, Igor Cauê Alves; Martins, Rafael Xavier; Seiwert, Bettina; Lechtenfeld, Oliver J.; Reemtsma, Thorsten; Farias, Davi Felipe

doi:10.1016/j.envpol.2021.117096

Cited by 13 publications

(7 citation statements)

References 59 publications

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“…Acute Toxicity Test. The fish embryo acute toxicity test was independently conducted with four peptides according to the OECD Guideline number 236 54 adapted for 96-well plates by Muniz et al 55 Zebrafish embryos with up to 3 hpf were exposed to 1 mg mL −1 of each sample. For each test and control sample, 20 wells were filled with 0.3 mL of solution and 1 embryo.…”

Section: ■ Conclusionmentioning

confidence: 99%

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

et al. 2022

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The outbreak caused by SARS-CoV-2 has taken many lives worldwide. Although vaccination has started, the development of drugs to either alleviate or abolish symptoms of COVID-19 is still necessary. Here, four synthetic peptides were assayed regarding their ability to protect Vero E6 cells from SARS-CoV-2 infection and their toxicity to human cells and zebrafish embryos. All peptides had some ability to protect cells from infection by SARS-CoV-2 with the D614G mutation. Molecular docking predicted the ability of all peptides to interact with and induce conformational alterations in the spike protein containing the D614G mutation. PepKAA was the most effective peptide, by having the highest docking score regarding the spike protein and reducing the SARS-CoV-2 plaque number by 50% (EC50) at a concentration of 0.15 mg mL–1. Additionally, all peptides had no toxicity to three lines of human cells as well as to zebrafish larvae and embryos. Thus, these peptides have potential activity against SARS-CoV-2, making them promising to develop new drugs to inhibit cell infection by SARS-CoV-2.

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Section: ■ Conclusionmentioning

confidence: 99%

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

et al. 2022

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“…However, moxidectin is highly toxic to aquatic organisms, such that inadvertent spillage of high volumes of product that ultimately enter waterways could have profound impacts, especially on fish. These may manifest as both acute toxicity and reproductive changes such as reduced egg hatching that could affect population dynamics in the longer term (Lumaret et al 2012;Mesa et al 2018;Muniz et al 2021). While more research into the ecotoxicological impacts of moxidectin are needed, in the short term, it would be prudent to clearly communicate to end-users that moxidectin pour-on should not be used near waterways, in volumes that inevitably lead to spillage, or during rain events that may lead to moxidectin being washed off the wombat or flooding of burrows.…”

Section: Ecotoxicity Potential With Indiscriminate Use Of Pour-on Mox...mentioning

confidence: 99%

Drug dose and animal welfare: important considerations in the treatment of wildlife

et al. 2022

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A recent publication in Parasitology Research by (Old et al. Parasitol Res 120:1077-1090 raises the topical and often controversial issue of the treatment of wildlife by personnel with little or no formal scientific training (e.g. wildlife carers). In a valuable contribution to the subject, Old and colleagues document a wide range of topical (pour-on) application doses and frequencies of moxidectin (Cydectin®) administered in situ to bare-nosed wombats (Vombatus ursinus) by members of the wildlife carer/treater community in southeast Australia to treat sarcoptic mange disease. This treatment occurred under minor use permits issued by the Australian Pesticides and Veterinary Management Authority (APVMA). These permits do not require veterinary supervision, although carers are registered and are expected to comply with the guidelines of this permit. The prevalence and severity of sarcoptic mange in wildlife is influenced by a variety of factors including mite biology, environmental conditions, population density, animal behaviour and immune susceptibility (Browne et al. Bioscience, 2021). In bare-nosed wombats, combinations of these elements play a substantial role in making the treatment of an already difficult disease more complex. (Moroni et al. Parasit Vectors 13:471, 2020) comment that any pharmacological treatment of freeranging wildlife must consider these factors when assessing their feasibility and implications, especially in the context of emerging drug resistance and potential long-term ecological impacts. As individuals with significant interest in sarcoptic mange and representing a range of professional research and veterinary expertise, we see value in providing expert commentary on this issue.

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“…Therefore, E-CBZ might not be the sole metabolite formed after CBZ exposure in zebrafish larvae. Further untargeted UHPLC-QTOF-MS investigations, as already performed for a variety of compounds exposed to zebrafish embryos [ 38 , 39 , 63 , 65 , 66 ], could aid in further understanding of the teratogenicity of CBZ and PHE. In this study, a targeted search was only performed for E-CBZ and HPPH, which are known to be teratogenic in mammals, with a targeted UPLC-QqQ-MS method.…”

Section: Discussionmentioning

confidence: 99%

Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

Bars

Hoyberghs

Valenzuela

et al. 2021

IJMS

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The zebrafish (Danio rerio) embryo is gaining interest as a bridging tool between in-vitro and in-vivo developmental toxicity studies. However, cytochrome P450 (CYP)-mediated drug metabolism in this model is still under debate. Therefore, we investigated the potential of zebrafish embryos and larvae to bioactivate two known anti-epileptics, carbamazepine (CBZ) and phenytoin (PHE), to carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), respectively. First, zebrafish were exposed to CBZ, PHE, E-CBZ and HPPH from 5¼- to 120-h post fertilization (hpf) and morphologically evaluated. Second, the formations of E-CBZ and HPPH were assessed in culture medium and in whole-embryo extracts at different time points by targeted LC-MS. Finally, E-CBZ and HPPH formation was also assessed in adult zebrafish liver microsomes and compared with those of human, rat, and rabbit. The present study showed teratogenic effects for CBZ and PHE, but not for E-CBZ and HPPH. No HPPH was detected during organogenesis and E-CBZ was only formed at the end of organogenesis. E-CBZ and HPPH formation was also very low-to-negligible in adult zebrafish compared with the mammalian species. As such, other metabolic pathways than those of mammals are involved in the bioactivation of CBZ and PHE, or, these anti-epileptics are teratogens and do not require bioactivation in the zebrafish.

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Moxidectin toxicity to zebrafish embryos: Bioaccumulation and biomarker responses

Cited by 13 publications

References 59 publications

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

Drug dose and animal welfare: important considerations in the treatment of wildlife

Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

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