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Cell-free hemoglobin (CFH) is released into the circulation of patients with severe sepsis and the levels of CFH are independently associated with mortality. CFH treatment increased cytotoxicity in the human tubular epithelial cell line HK-2. To better model the intact kidney, we cultured human kidney organoids derived from induced pluripotent stem cells. We treated human kidney organoids grown using both three-dimensional and transwell protocols with CFH for 48\u2005h. We found evidence for increased tubular toxicity, oxidative stress, mitochondrial fragmentation, endothelial cell injury and injury-associated transcripts compared to those of the untreated control group. To evaluate the protective effect of clinically available small molecules, we co-treated CFH-injured organoids with ascorbate (vitamin C) or acetaminophen for 48\u2005h. We found significantly decreased toxicity, preservation of endothelial cells and reduced mitochondrial fragmentation in the group receiving ascorbate following CFH treatment. This study provides direct evidence that ascorbate or ascorbic acid protects human kidney cells from CFH-induced damage such as that in sepsis-associated acute kidney injury.<\/jats:p>","DOI":"10.1242\/dmm.050342","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T09:40:40Z","timestamp":1699522840000},"source":"Crossref","is-referenced-by-count":9,"title":["Ascorbate protects human kidney organoids from damage induced by cell-free hemoglobin"],"prefix":"10.1242","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6406-077X","authenticated-orcid":false,"given":"Julie","family":"Bejoy","sequence":"first","affiliation":[{"name":"Vanderbilt University Medical Center 1 Department of Medicine, Division of Nephrology and Hypertension , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5288-8991","authenticated-orcid":false,"given":"Justin M.","family":"Farry","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center 1 Department of Medicine, Division of Nephrology and Hypertension , , Nashville, TN 37232 , USA"},{"name":"Vanderbilt University 2 Department of Biomedical Engineering , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-0223","authenticated-orcid":false,"given":"Eddie S.","family":"Qian","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center 1 Department of Medicine, Division of Nephrology and Hypertension , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis H.","family":"Dearing","sequence":"additional","affiliation":[{"name":"Vanderbilt University 3 Vanderbilt Experimental Research Training Inclusion Community Engagement Skills (VERTICES) program , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9429-4702","authenticated-orcid":false,"given":"Lorraine B.","family":"Ware","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center 4 Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine , , Nashville, TN 37232 , USA"},{"name":"Vanderbilt University Medical Center 5 Department of Pathology, Microbiology and Immunology , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-6507","authenticated-orcid":false,"given":"Julie A.","family":"Bastarache","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center 4 Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine , , Nashville, TN 37232 , USA"},{"name":"Vanderbilt University Medical Center 5 Department of Pathology, Microbiology and Immunology , , Nashville, TN 37232 , USA"},{"name":"Vanderbilt University Medical Center 6 Department of Cell Biology , , Nashville, TN 37232 , USA"},{"name":"U.S. Department of Veterans Affairs 7 , Nashville, TN 37212 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5812-1812","authenticated-orcid":false,"given":"Lauren E.","family":"Woodard","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center 1 Department of Medicine, Division of Nephrology and Hypertension , , Nashville, TN 37232 , USA"},{"name":"Vanderbilt University 2 Department of Biomedical Engineering , , Nashville, TN 37232 , USA"},{"name":"U.S. Department of Veterans Affairs 7 , Nashville, TN 37212 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"key":"2024011507411203000_DMM050342C1","doi-asserted-by":"publisher","first-page":"R125","DOI":"10.1186\/cc11425","article-title":"Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome","volume":"16","author":"Adamzik","year":"2012","journal-title":"Crit. 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