{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:57:43Z","timestamp":1792634263124,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK123097"],"award-info":[{"award-number":["R01 DK123097"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Protocols"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ferroptosis is iron\u2010dependent, lipid peroxidation\u2013driven, regulated cell death that is triggered when cellular glutathione peroxidase 4 (GPX4)\u2010mediated cellular defense is insufficient to prevent pathologic accumulation of toxic lipid peroxides. Ferroptosis is implicated in various human pathologies, including neurodegeneration, chemotherapy\u2010resistant cancers, ischemia\u2010reperfusion injury, and acute and chronic kidney diseases. Despite the fact that the ferroptotic process has been rigorously interrogated in multiple preclinical models, the lack of specific and readily available biomarkers to detect ferroptosis <jats:italic>in vivo<\/jats:italic> in mouse models makes it challenging to delineate its contribution to key pathologic events <jats:italic>in vivo<\/jats:italic>. Critical steps to practically evaluate ferroptosis include, but are not limited to, detecting increased cell death and pathologic accumulation of toxic lipid peroxides and testing augmentation of observed pathologic events by genetic inhibition of the glutathione\u2010GPX4 axis or mitigation of the pathologic process by ferroptosis inhibitors. Here, we describe methods to evaluate these key features of the ferroptotic process in mice <jats:italic>in vivo<\/jats:italic>. Specifically, we describe methods to detect toxic lipid peroxides (4\u2010hydroxynonenal) and cell death (based on terminal deoxynucleotidyl transferase dUTP nick end labeling staining) as well as a protocol to pharmacologically inhibit ferroptotic stress using liproxstatin\u20101. These protocols provide tools for understanding the ferroptotic process in mouse genetic or disease models. \u00a9 2022 Wiley Periodicals LLC.<\/jats:p><jats:p><jats:bold>Basic Protocol 1<\/jats:bold>: How to use liproxstatin\u20101<\/jats:p><jats:p><jats:bold>Basic Protocol 2<\/jats:bold>: How to evaluate ferroptosis in mouse kidneys<\/jats:p>","DOI":"10.1002\/cpz1.413","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T18:40:20Z","timestamp":1649184020000},"source":"Crossref","is-referenced-by-count":19,"title":["<i>In Vivo<\/i> Assessment of Ferroptosis and Ferroptotic Stress in Mice"],"prefix":"10.1002","volume":"2","author":[{"given":"Kana","family":"Ide","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine Duke University School of Medicine  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3285-8613","authenticated-orcid":false,"given":"Tomokazu","family":"Souma","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Duke University School of Medicine  Durham North Carolina"},{"name":"Duke Regeneration Center  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.032"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2020.03.014"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.10.007"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.637162"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2020.08.010"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01299"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.049"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3064"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010017\u20100012\u20104"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840210534"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201025377\u2010x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01641"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68603"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6943"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u201000324\u20108"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1415518111"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010017\u20102547\u20104"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010020\u201000691\u2010x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.021"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.044"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.23958"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010"}],"container-title":["Current Protocols"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpz1.413","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpz1.413","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/currentprotocols.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpz1.413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T10:43:36Z","timestamp":1692960216000},"score":1,"resource":{"primary":{"URL":"https:\/\/currentprotocols.onlinelibrary.wiley.com\/doi\/10.1002\/cpz1.413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1002\/cpz1.413"],"URL":"https:\/\/doi.org\/10.1002\/cpz1.413","archive":["Portico"],"relation":{},"ISSN":["2691-1299","2691-1299"],"issn-type":[{"value":"2691-1299","type":"print"},{"value":"2691-1299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4]]},"article-number":"e413"}}