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We have characterized the kidney lipidome in an experimental nephrotoxic AKI induced in mice using folic acid and assessed the impact of the ferroptosis inhibitor Ferrostatin\u20101. Matrix\u2010assisted laser desorption\/ionization (MALDI) imaging mass spectrometry (IMS) was used to assess kidney lipidomics and it discriminated between glomeruli, medulla, and cortex in control kidneys, AKI kidneys, and AKI\u2009+\u2009Ferrostatin\u20101 kidneys. Out of 139 lipid species from 16 classes identified, 29 (20.5%) showed significant differences between control and AKI at 48\u2009h. Total PE and lyso\u2010sulfatide species decreased, while phosphatidylinositol (PI) species increased in AKI. Dysregulated mRNA levels for <jats:italic>Pemt<\/jats:italic>, <jats:italic>Pgs1<\/jats:italic>, <jats:italic>Cdipt<\/jats:italic>, and <jats:italic>Tamm41<\/jats:italic>, relevant to lipid metabolism, were in line with the lipid changes observed. Ferrostatin\u20101 prevented AKI and some AKI\u2010associated changes in lipid levels, such as the decrease in PE and lyso\u2010sulfatide species, without changing the gene expression of lipid metabolism enzymes. In conclusion, changes in the kidney lipid composition during nephrotoxic AKI are associated with differential gene expression of lipid metabolism enzymes and are partially prevented by Ferrostatin\u20101. \u00a9 2022 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5882","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T10:17:57Z","timestamp":1644747477000},"page":"285-299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Ferrostatin\u20101 modulates dysregulated kidney lipids in acute kidney injury"],"prefix":"10.1002","volume":"257","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1135-0842","authenticated-orcid":false,"given":"Luc\u00eda","family":"Mart\u00edn\u2010Saiz","sequence":"first","affiliation":[{"name":"Department of Physical Chemistry Faculty of Science and Technology, University of the Basque Country (UPV\/EHU)  Leioa Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Guerrero\u2010Mauvecin","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Nephrology. 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