{"id":"feb6a15b-d325-5686-bdd4-0f4d0e028c66","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-metal-gsh-protection","predicate":"preserves","statement":"At 5 micromolar, fisetin limited iron- or copper-potentiated glutathione loss and cell death in glutamate-challenged mouse HT22 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"2c0d2f0b-c23d-50ce-9ed6-360120367b13","mechanism_event_label":"Protection depended on the way oxidative stress was induced.","subject":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"object":{"id":"92271d0d-c41f-5783-ad63-88644e2e960b","slug":"mouse-ht22-glutathione-content","display_name":"Mouse HT22 cellular glutathione content","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2c0d2f0b-c23d-50ce-9ed6-360120367b13","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-metal-gsh-protection-event","event_type":"observed_relationship","label":"Protection depended on the way oxidative stress was induced.","description":"At 5 micromolar, fisetin limited iron- or copper-potentiated glutathione loss and cell death in glutamate-challenged mouse HT22 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"92271d0d-c41f-5783-ad63-88644e2e960b","slug":"mouse-ht22-glutathione-content","display_name":"Mouse HT22 cellular glutathione content","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"2a870bb5-05a0-5e51-a70c-a9a843a8b571","slug":"copper-ii","display_name":"Copper(II) ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not a dietary deficiency experiment or evidence of systemic metal removal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Protection depended on the way oxidative stress was induced.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"88066819-7893-5dfe-aae0-74f6cb750067","evidence_kind":"source_excerpt","locator":"Lines 152-158","start_line":152,"end_line":158,"excerpt":"## fisetin-metal-gsh-protection\nProtection depended on the way oxidative stress was induced.\nAt 5 micromolar, fisetin limited iron- or copper-potentiated glutathione loss and cell death in glutamate-challenged mouse HT22 cells.\nModel: Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar.\nLimitations: Not a dietary deficiency experiment or evidence of systemic metal removal.\nEvidence access: Primary full text\nModulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113","model_system":"Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"1108bfff-6504-5152-a51f-ff3d7c27c282","stable_key":"import-74ef5bba-ee14-531c-b1bf-d1f297c56bb6","title":"Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"c30e0764cd34bd062cfcbfaf32357ef29dfda30e7d4153c545178140f5054e09","revision_id":"40ff52c0-f4b9-5820-8abb-ff002c6364a4","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}