{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:46:32Z","timestamp":1773873992475,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2314-B-037-069-MY3"],"award-info":[{"award-number":["MOST 109-2314-B-037-069-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kaohsiung Medical University, Taiwan","award":["KMU- DK(B)110003-5TC"],"award-info":[{"award-number":["KMU- DK(B)110003-5TC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Kidney disease patients may have concurrent chronic kidney disease-associated mineral bone disorder and hypertension. Cardiovascular disease (CVD) and neuropathy occur due to kidney failure-induced accumulation of uremic toxins in the body. Indoxyl sulfate (IS), a product of indole metabolism in the liver, is produced from tryptophan by the intestinal flora and is ultimately excreted through the kidneys. Hemodialysis helps renal failure patients eliminate many nephrotoxins, except for IS, which leads to a poor prognosis. Although the impacts of IS on cardiac and renal development have been well documented using mouse and rat models, other model organisms, such as zebrafish, have rarely been studied. The zebrafish genome shares at least 70% similarity with the human genome; therefore, zebrafish are ideal model organisms for studying vertebrate development, including renal development. In this study, we aimed to investigate the impact of IS on the development of zebrafish embryos, especially cardiac and renal development. At 24 h postfertilization (hpf), zebrafish were exposed to IS at concentrations ranging from 2.5 to 10 mM. IS reduced survival and the hatching rate, caused cardiac edema, increased mortality, and shortened the body length of zebrafish embryos. In addition, IS decreased heart rates and renal function. IS affected zebrafish development via the ROS and MAPK pathways, which subsequently led to inflammation in the embryos. The results suggest that IS interferes with cardiac and renal development in zebrafish embryos, providing new evidence about the toxicity of IS to aquatic organisms and new insights for the assessment of human health risks. Accordingly, we suggest that zebrafish studies can ideally complement mouse model studies to allow the simultaneous and comprehensive investigation of the physiological impacts of uremic endotheliotoxins, such as IS, on cardiac and renal development.<\/jats:p>","DOI":"10.3390\/antiox11020400","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:26:41Z","timestamp":1645043201000},"page":"400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Zebrafish Model-Based Assessment of Indoxyl Sulfate-Induced Oxidative Stress and Its Impact on Renal and Cardiac Development"],"prefix":"10.3390","volume":"11","author":[{"given":"Paul Wei-Hua","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Taipei Veterans General Hospital Yuli Branch, Hualien 981, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tong University, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping-Hsun","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Hao","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tien-Li","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hui","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-4138","authenticated-orcid":false,"given":"Hugo You-Hsien","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan"},{"name":"Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun-Tai","family":"Lee","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4436-7464","authenticated-orcid":false,"given":"Yau-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tamkang University, Tamsui, New Taipei City 251, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7307-2468","authenticated-orcid":false,"given":"Chien-Chih","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangta","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1681\/ASN.2005101085","article-title":"Chronic kidney disease and mortality risk: A systematic review","volume":"17","author":"Tonelli","year":"2006","journal-title":"J. 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