{"id":"388fea0b-a68f-54bb-8910-57893815de0b","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cardiac-gpx4","predicate":"preserves_expression","statement":"Fisetin restored GPX4 protein and glutathione while reducing lipid-oxidation markers in doxorubicin-exposed rat hearts and H9c2 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"03a00c5d-cbf6-5396-a754-20ff3b64fdf7","mechanism_event_label":"A selenium-containing defense pathway accompanied protection.","subject":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"object":{"id":"cc0ebb24-b978-598b-a9aa-8c5b99eab542","slug":"rat-gpx4","display_name":"Rat glutathione peroxidase 4 / Gpx4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"03a00c5d-cbf6-5396-a754-20ff3b64fdf7","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-cardiac-gpx4-event","event_type":"observed_relationship","label":"A selenium-containing defense pathway accompanied protection.","description":"Fisetin restored GPX4 protein and glutathione while reducing lipid-oxidation markers in doxorubicin-exposed rat hearts and H9c2 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":"cc0ebb24-b978-598b-a9aa-8c5b99eab542","slug":"rat-gpx4","display_name":"Rat glutathione peroxidase 4 / Gpx4","entity_type_key":"protein"},"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":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat model; H9c2 assays used 40 micromolar fisetin with 1 micromolar doxorubicin for 24 hours.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not establish selenium replacement or preservation of anticancer efficacy.","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":"A selenium-containing defense pathway accompanied protection.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2a44838e-d876-570d-8219-35450c66c91d","evidence_kind":"source_excerpt","locator":"Lines 416-422","start_line":416,"end_line":422,"excerpt":"## fisetin-cardiac-gpx4\nA selenium-containing defense pathway accompanied protection.\nFisetin restored GPX4 protein and glutathione while reducing lipid-oxidation markers in doxorubicin-exposed rat hearts and H9c2 cells.\nModel: Rat model; H9c2 assays used 40 micromolar fisetin with 1 micromolar doxorubicin for 24 hours.\nLimitations: Does not establish selenium replacement or preservation of anticancer efficacy.\nEvidence access: Primary full text\nFisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480","model_system":"Rat model; H9c2 assays used 40 micromolar fisetin with 1 micromolar doxorubicin for 24 hours.","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. 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