{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:38:16Z","timestamp":1789148296845,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011607","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000}}],"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"crossref","award":["KJ2020A0153"],"award-info":[{"award-number":["KJ2020A0153"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81572801"],"award-info":[{"award-number":["81572801"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Scientific Research from Anhui Medical University","award":["XJ202005"],"award-info":[{"award-number":["XJ202005"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Iron is a trace metal element that is essential for the survival of cells and parasites. The role of iron in cerebral toxoplasmosis (CT) is still unclear. Deferiprone (DFP) is the orally active iron chelator that binds iron in a molar ratio of 3:1 (ligand:iron) and promotes urinary iron excretion to remove excess iron from the body. The aims of this experiment were to observe the alterations in iron in brains with<jats:italic>Toxoplasma gondii<\/jats:italic>(<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>) acute infections and to investigate the mechanism of ferroptosis in CT using DFP. We established a cerebral toxoplasmosis model<jats:italic>in vivo<\/jats:italic>using TgCtwh3, the dominant strains of which are prevalent in China, and treated the mice with DFP at a dose of 75 mg\/kg\/d. Meanwhile, we treated the HT-22 cells with 100 \u03bcM DFP for half an hour and then infected cells with TgCtwh3<jats:italic>in vitro<\/jats:italic>. A qRT-PCR assay of<jats:italic>Tg<\/jats:italic>SAG1 levels showed a response to the<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>burden. We used inductively coupled plasma mass spectrometry, an iron ion assay kit, Western blot analysis, glutathione and glutathione disulfide assay kits, a malonaldehyde assay kit, and immunofluorescence to detect the ferroptosis-related indexes in the mouse hippocampus and HT-22 cells. The inflammatory factors interferon-\u03b3, tumor necrosis factor-\u03b1, transforming growth factor-\u03b2, and arginase 1 in the hippocampus and cells were detected using the Western blot assay. Hematoxylin and eosin staining, electron microscopy, and the Morris water maze experiment were used to evaluate the brain injuries of the mice. The results showed that TgCtwh3 infection is followed by the activation of ferroptosis-related signaling pathways and hippocampal pathological damage in mice. The use of DFP led to ferroptosis resistance and attenuated pathological changes, inflammatory reactions and<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>burden of the mice, prolonging their survival time. The HT-22 cells with TgCtwh3 activated the ferroptosis pathway and was inhibit by DFP<jats:italic>in vitro<\/jats:italic>. In TgCtwh3-infected cells, inflammatory response and mitochondrial damage were severe, but these effects could be reduced by DFP. Our study elucidates the mechanism by which<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>interferes with the host\u2019s iron metabolism and activates ferroptosis, complementing the pathogenic mechanism of CT and further demonstrating the potential value of DFP for the treatment of CT.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011607","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T17:42:25Z","timestamp":1693503745000},"page":"e0011607","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Iron-overload-induced ferroptosis in mouse cerebral toxoplasmosis promotes brain injury and could be inhibited by 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