{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:17:52Z","timestamp":1792448272856,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201507040037"],"award-info":[{"award-number":["201507040037"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>With the aim to explore the possibility to generate a zebrafish model of renal fibrosis, in this study the fibrogenic renal effect of aristolochic acid I (AAI) after immersion was assessed. This compound is highly nephrotoxic able to elicit renal fibrosis after exposure of rats and humans. Our results reveal that larval zebrafish at 15 days dpf (days post-fertilization) exposed for 8 days to 0.5 \u00b5M AAI showed clear signs of AKI (acute kidney injury). The damage resulted in the relative loss of the functional glomerular filtration barrier. Conversely, we did not observe any deposition of collagen, nor could we immunodetect \u03b1-SMA, a hallmark of myofibroblasts, in the tubules. In addition, no increase in gene expression of fibrogenesis biomarkers after whole animal RNA extraction was found. As zebrafish have a high capability for tissue regeneration possibly impeding fibrogenic processes, we also used a tert\u2212\/\u2212 zebrafish line exhibiting telomerase deficiency and impaired tissue homeostasis. AAI-treated tert\u2212\/\u2212 larvae displayed an increased sensitivity towards 0.5 \u00b5M AAI. Importantly, after AAI treatment a mild collagen deposition could be found in the tubules. The outcome implies that sustained AKI induced by nephrotoxic compounds combined with defective tert\u2212\/\u2212 stem cells can produce a fibrotic response.<\/jats:p>","DOI":"10.3390\/toxins12040217","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T13:39:34Z","timestamp":1585834774000},"page":"217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Nephrotoxic Effects in Zebrafish after Prolonged Exposure to Aristolochic Acid"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1648-2820","authenticated-orcid":false,"given":"Xixin","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O &amp; N II Herestraat 49-Box 824, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7460-3336","authenticated-orcid":false,"given":"Arianna","family":"Giusti","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O &amp; N II Herestraat 49-Box 824, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3678-5941","authenticated-orcid":false,"given":"Annelii","family":"Ny","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O &amp; N II Herestraat 49-Box 824, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9989-9567","authenticated-orcid":false,"given":"Peter A.","family":"de Witte","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O &amp; N II Herestraat 49-Box 824, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev-physiol-022516-034227","article-title":"Mechanisms of Renal Fibrosis","volume":"80","author":"Humphreys","year":"2018","journal-title":"Annual Review of Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1152\/ajprenal.00379.2006","article-title":"In Vitro Models of TGF-\u03b2-Induced FIbrosis Suitable for High-Throughput Screening of Antifibrotic Agents","volume":"293","author":"Xu","year":"2007","journal-title":"Ren. 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