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Heme oxygenase\u20101 (HO\u20101) has been reported to play an important role against renal injuries. Hemin, a HO\u20101 inducer and anti\u2010porphyria medicine, may have a promising effect against CIN. In this study, we aim to investigate the effect of hemin on CIN model and the underlying molecular mechanisms in human proximal tubule epithelial cells (HK\u20102). To mimic a common condition in percutaneous coronary intervention (PCI) patients, CIN was induced by intravenous iopromide in high\u2010fat fed diabetic rats. We found hemin, given right before iopromide, mitigated CIN with enhanced antioxidative capacity and reduced oxidative stress. HK\u20102 cells insulted by iopromide demonstrated decreased cell vitality and rising reactive oxygen species (ROS), which could also be inhibited by hemin. The effects of hemin involved a key molecule in ferroptosis, glutathione peroxidase (GPX4), whose down\u2010expression by small interfering RNA (siRNA) reversed the effect of hemin on HK\u20102 cells. Furthermore, hemin's induction of GPX4 involved HO\u20101 and nuclear factor erythroid 2\u2010related factor 2 (Nrf2). Either HO\u20101 or Nrf2 inhibitor prevented hemin's effect on GPX4 to a comparable extent, and over\u2010expression of Nrf2 increased GPX4 expression. Moreover, intervention of ferroptosis inhibitor liproxstatin\u20101 also alleviated CIN in vivo. Therefore, we showed hemin mitigated CIN, inhibiting oxidative stress and ferroptosis, by upregulation of GPX4 via activation of HO\u20101\/Nrf2. Hemin, as a clinical medicine, has a translational significance in treating CIN, and anti\u2010ferroptosis is a potential therapeutic strategy for CIN.<\/jats:p>","DOI":"10.1111\/1440-1681.13673","type":"journal-article","created":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T15:03:03Z","timestamp":1653231783000},"page":"858-870","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Hemin mitigates contrast\u2010induced nephropathy by inhibiting ferroptosis via<scp>HO<\/scp>\u20101\/Nrf2\/<scp>GPX4<\/scp>pathway"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-0682","authenticated-orcid":false,"given":"Zhao","family":"Gao","sequence":"first","affiliation":[{"name":"Medical and Healthcare Center, Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University Haikou Hainan 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Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Laboratory Liang Ping People's Hospital of Chongqing Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical 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