{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:36:59Z","timestamp":1780637819435,"version":"3.54.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"30","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,25]]},"abstract":"<jats:p>Propofol is the most commonly used intravenous anesthesia in clinical anesthesia and is widely used in various surgeries. Several clinical and preclinical studies have found that propofol can produce neurotoxicity. However, the underlying molecular mechanisms have not been fully elucidated. Ferroptosis is considered to be a new form of cell death. Here, we reveal a new potential mechanism by which ferroptosis is involved in propofol-induced neurotoxicity. We used SH-SY5Y cells as experimental materials to investigate whether propofol produces neurotoxicity by inducing ferroptosis. Our results suggest that propofol significantly causes cytoplasmic iron accumulation through the nuclear receptor coactivator 4-induced ferritin autophagy pathway. Iron overload further induces ferroptosis through the production of lipid reactive oxygen species. Propofol significantly down-regulates the expression of cystine\/glutamate antiporter, glutathione peroxidase 4, and glutathione\/glutathione disulfide ratio, and up-regulates the expression of acyl-CoA synthetase long-chain family member 4 and NADP<jats:sup>+<\/jats:sup>\/nicotinamide adenine dinucleotide phosphate ratio, which were important makers of ferroptosis. Fer-1, an inhibitor of ferroptosis, could significantly ameliorate the ferroptosis induced by propofol. These data further demonstrate the complexity of the occurrence of propofol-induced neurotoxicity. Inhibiting ferroptosis may be a new strategy for preventing neurotoxicity in the future.<\/jats:p>","DOI":"10.1097\/md.0000000000043390","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T10:00:24Z","timestamp":1753956024000},"page":"e43390","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Propofol is involved in neurotoxicity by mediating the occurrence of ferroptosis"],"prefix":"10.1097","volume":"104","author":[{"given":"Lei","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Xingtai People\u2019s Hospital of Hebei Medical University, Xingtai, Hebei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Xingtai People\u2019s Hospital of Hebei Medical University, Xingtai, Hebei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Xingtai People\u2019s Hospital of Hebei Medical University, Xingtai, Hebei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"He","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Xingtai People\u2019s Hospital of Hebei Medical University, Xingtai, Hebei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Xingtai People\u2019s Hospital of Hebei Medical University, Xingtai, Hebei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Heze Medical College, Heze, Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-5485","authenticated-orcid":false,"given":"Xinyu","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Xingtai People\u2019s Hospital of Hebei Medical University, Xingtai, Hebei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20251014","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s40263-015-0259-6","article-title":"Propofol: a review of its role in pediatric anesthesia and sedation.","volume":"29","author":"Chidambaran","year":"2015","journal-title":"CNS Drugs"},{"key":"R2-20251014","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/j.1365-2044.1982.tb01753.x","article-title":"An adverse reaction to the administration of disoprofol (Diprivan).","volume":"37","author":"Briggs","year":"1982","journal-title":"Anaesthesia"},{"key":"R3-20251014","doi-asserted-by":"crossref","first-page":"922","DOI":"10.3389\/fnins.2018.00922","article-title":"Propofol inhibits cerebellar parallel fiber-purkinje cell synaptic transmission via activation of presynaptic GABA(B) receptors in vitro in mice.","volume":"12","author":"Xuan","year":"2018","journal-title":"Front Neurosci"},{"key":"R4-20251014","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s40262-018-0672-3","article-title":"Clinical pharmacokinetics and pharmacodynamics of propofol.","volume":"57","author":"Sahinovic","year":"2018","journal-title":"Clin Pharmacokinet"},{"key":"R5-20251014","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2174\/0929867003375335","article-title":"Propofol in anesthesia. 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