Yuping Wang, Min Zhou, Jing Wang, Chu-Fang Lin, Xiang-li Gao, Li Zhang, Wenshui Yao, Longxin Zhang
{"title":"氟比洛芬酯对斑马鱼胚胎的发育性心脏毒性和肝毒性。","authors":"Yuping Wang, Min Zhou, Jing Wang, Chu-Fang Lin, Xiang-li Gao, Li Zhang, Wenshui Yao, Longxin Zhang","doi":"10.1089/adt.2021.127","DOIUrl":null,"url":null,"abstract":"Flurbiprofen axetil (FA) is a nonsteroidal targeted analgesic and widely used for postoperative analgesia and cancer analgesia. Extensive works have been done in the evaluation of FA's clinical analgesic effect on adults. Along with the increase of FA usage, the potential toxicity and molecular mechanism in embryo development need to be better understood. In this article, multiple embryonic development indexes of zebrafish were introduced to evaluate the FA toxicity to provide clinical guidance for gravidas medicine. We performed a zebrafish embryo toxicity (ZFET) test by exposing embryos to a series of concentration gradients of FA medium starting from 24 hours postfertilization (hpf). The mortality rate, hatching rate, and malformation rate of drug-treated zebrafish were assessed at 72, 96, and 120 hpf. Effects of ≤10% lethal concentration (LC10) of FA on embryogenesis were evaluated by eye area, body length, and yolk sac area. A 0.5 μg/mL or fewer FA treatment did not show any adverse effects, but the LC10 FA significantly caused zebrafish malformation. Organ disorders, including slow heart rate, enlarged pericardium, and liver atrophy, were found in the dysplasia individuals when compared with control. TUNEL assay suggested that apoptotic cells in malformation embryos were produced by FA and the increasing dosage exacerbated apoptosis. Quantitative real-time polymerase chain reaction revealed that expressions of cardiac development-associated transcription factors, liver development-related genes, and apoptosis regulating genes were aberrant. These results indicate that the ZFET can be applied in the FA toxicity test, and a low lethal dose of FA is harmful to zebrafish embryogenesis, especially in embryo carcinogenesis and hepatogenesis.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Developmental Cardiotoxicity and Hepatotoxicity of Flurbiprofen Axetil to Zebrafish Embryo.\",\"authors\":\"Yuping Wang, Min Zhou, Jing Wang, Chu-Fang Lin, Xiang-li Gao, Li Zhang, Wenshui Yao, Longxin Zhang\",\"doi\":\"10.1089/adt.2021.127\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Flurbiprofen axetil (FA) is a nonsteroidal targeted analgesic and widely used for postoperative analgesia and cancer analgesia. Extensive works have been done in the evaluation of FA's clinical analgesic effect on adults. Along with the increase of FA usage, the potential toxicity and molecular mechanism in embryo development need to be better understood. In this article, multiple embryonic development indexes of zebrafish were introduced to evaluate the FA toxicity to provide clinical guidance for gravidas medicine. We performed a zebrafish embryo toxicity (ZFET) test by exposing embryos to a series of concentration gradients of FA medium starting from 24 hours postfertilization (hpf). The mortality rate, hatching rate, and malformation rate of drug-treated zebrafish were assessed at 72, 96, and 120 hpf. Effects of ≤10% lethal concentration (LC10) of FA on embryogenesis were evaluated by eye area, body length, and yolk sac area. A 0.5 μg/mL or fewer FA treatment did not show any adverse effects, but the LC10 FA significantly caused zebrafish malformation. Organ disorders, including slow heart rate, enlarged pericardium, and liver atrophy, were found in the dysplasia individuals when compared with control. TUNEL assay suggested that apoptotic cells in malformation embryos were produced by FA and the increasing dosage exacerbated apoptosis. Quantitative real-time polymerase chain reaction revealed that expressions of cardiac development-associated transcription factors, liver development-related genes, and apoptosis regulating genes were aberrant. 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Developmental Cardiotoxicity and Hepatotoxicity of Flurbiprofen Axetil to Zebrafish Embryo.
Flurbiprofen axetil (FA) is a nonsteroidal targeted analgesic and widely used for postoperative analgesia and cancer analgesia. Extensive works have been done in the evaluation of FA's clinical analgesic effect on adults. Along with the increase of FA usage, the potential toxicity and molecular mechanism in embryo development need to be better understood. In this article, multiple embryonic development indexes of zebrafish were introduced to evaluate the FA toxicity to provide clinical guidance for gravidas medicine. We performed a zebrafish embryo toxicity (ZFET) test by exposing embryos to a series of concentration gradients of FA medium starting from 24 hours postfertilization (hpf). The mortality rate, hatching rate, and malformation rate of drug-treated zebrafish were assessed at 72, 96, and 120 hpf. Effects of ≤10% lethal concentration (LC10) of FA on embryogenesis were evaluated by eye area, body length, and yolk sac area. A 0.5 μg/mL or fewer FA treatment did not show any adverse effects, but the LC10 FA significantly caused zebrafish malformation. Organ disorders, including slow heart rate, enlarged pericardium, and liver atrophy, were found in the dysplasia individuals when compared with control. TUNEL assay suggested that apoptotic cells in malformation embryos were produced by FA and the increasing dosage exacerbated apoptosis. Quantitative real-time polymerase chain reaction revealed that expressions of cardiac development-associated transcription factors, liver development-related genes, and apoptosis regulating genes were aberrant. These results indicate that the ZFET can be applied in the FA toxicity test, and a low lethal dose of FA is harmful to zebrafish embryogenesis, especially in embryo carcinogenesis and hepatogenesis.
期刊介绍:
ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application.
ASSAY and Drug Development Technologies coverage includes:
-Assay design, target development, and high-throughput technologies-
Hit to Lead optimization and medicinal chemistry through preclinical candidate selection-
Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis-
Approaches to assays configured for gene families, inherited, and infectious diseases-
Assays and strategies for adapting model organisms to drug discovery-
The use of stem cells as models of disease-
Translation of phenotypic outputs to target identification-
Exploration and mechanistic studies of the technical basis for assay and screening artifacts