{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:22:58Z","timestamp":1784892178789,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860282, 31900597, 31872562, 32072969"],"award-info":[{"award-number":["81860282, 31900597, 31872562, 32072969"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Due to an increasing number of abused drugs dumped into the wastewater, more and more drugs are detected in the water environment, which may affect the survival of aquatic organisms. Lenvatinib is a multi\u2010targeted tyrosine kinase inhibitor, and is clinically used to treat differentiated thyroid cancer, renal epithelial cell carcinoma and liver cancer. However, there are few reports on the effects of lenvatinib in embryos development. In this study, zebrafish embryos were used to evaluate the effect of lenvatinib on cardiovascular development. Well\u2010developed zebrafish embryos were selected at 6\u00a0h post fertilization (hpf) and exposed to 0.05\u2009mg\/L, 0.1\u00a0mg\/L and 0.2\u00a0mg\/L lenvatinib up to 72 hpf. The processed embryos demonstrated cardiac edema, decreased heart rate, prolonged SV\u2010BA distance, inhibited angiogenesis, and blocked blood circulation. Lenvatinib caused cardiac defects in the whole stage of cardiac development and increased the apoptosis of cardiomyocyte. Oxidative stress in the processed embryos was accumulated and inhibiting oxidative stress could rescue cardiac defects induced by lenvatinib. Additionally, we found that lenvatinib downregulated Notch signaling, and the activation of Notch signaling could rescue cardiac developmental defects and downregulate oxidative stress level induced by lenvatinib. Our results suggested that lenvatinib might induce cardiac developmental toxicity through inducing Notch mediated\u2010oxidative stress generation, raising concerns about the harm of exposure to lenvatinib in aquatic organisms.<\/jats:p>","DOI":"10.1002\/tox.23485","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T11:44:29Z","timestamp":1643975069000},"page":"1310-1320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lenvatinib induces cardiac developmental toxicity in zebrafish embryos through regulation of Notch mediated\u2010oxidative stress generation"],"prefix":"10.1002","volume":"37","author":[{"given":"Jieping","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Healthy Mariculture for the East China Sea Ministry of Agriculture and Rural Affairs, Jimei University  Xiamen Fujian 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