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The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.
Li, Ji-Tong; Zhang, Yao-Dong; Song, Xiao-Rui; Li, Rui-Jing; Yang, Wei-Li; Tian, Ming; Zhang, Shu-Feng; Cao, Guang-Hai; Song, Lu-Lu; Chen, Yu-Ming; Liu, Cui-Hua.
  • Li JT; Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
  • Zhang YD; Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Zhengzhou, China.
  • Song XR; Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
  • Li RJ; Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
  • Yang WL; Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
  • Tian M; Henan Neurodevelopment Engineering Research Center for Children, Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
  • Zhang SF; Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Zhengzhou, China.
  • Cao GH; Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Zhengzhou, China.
  • Song LL; Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Zhengzhou, China.
  • Chen YM; School of Public Health, Zhengzhou University, Zhengzhou, China.
  • Liu CH; School of Public Health, Xinxiang Medical University, Xinxiang, China.
J Appl Toxicol ; 42(10): 1688-1700, 2022 10.
Article Dans Anglais | MEDLINE | ID: covidwho-2013548
ABSTRACT
The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.
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Texte intégral: Disponible Collection: Bases de données internationales Base de données: MEDLINE Sujet Principal: Polluants chimiques de l'eau / Type d'étude: Études expérimentales Les sujets: Variantes Limites du sujet: Animaux langue: Anglais Revue: J Appl Toxicol Année: 2022 Type de document: Article Pays d'affiliation: Jat.4336

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Texte intégral: Disponible Collection: Bases de données internationales Base de données: MEDLINE Sujet Principal: Polluants chimiques de l'eau / Type d'étude: Études expérimentales Les sujets: Variantes Limites du sujet: Animaux langue: Anglais Revue: J Appl Toxicol Année: 2022 Type de document: Article Pays d'affiliation: Jat.4336