{"id":"a7b37ff6-9dfb-5b11-969d-974df3ab460c","stable_key":"59b18080-c560-563d-abc5-bac4ee82a27c:ergothioneine-nrf2-dependence","predicate":"weakens","statement":"Nrf2 silencing supported Nrf2 dependence of ergothioneine protection in the cisplatin ototoxicity study.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7e537ea7-e58e-5dbe-b53e-80612755ab81","mechanism_event_label":"Disabling antioxidant signaling weakened protection.","subject":{"id":"cf22281c-8f55-5b89-8a49-a2edca7d202f","slug":"cochlear-model-nrf2-silencing","display_name":"Nrf2 silencing in the cochlear-cell experimental model","entity_type_key":"cellular_process"},"object":{"id":"3e9cd0e3-cb67-59f2-abb2-eefb8d9dad2a","slug":"cochlear-ergo-antioxidant-response","display_name":"Ergothioneine-associated cochlear-cell antioxidant response","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7e537ea7-e58e-5dbe-b53e-80612755ab81","stable_key":"59b18080-c560-563d-abc5-bac4ee82a27c:ergothioneine-nrf2-dependence-event","event_type":"observed_relationship","label":"Disabling antioxidant signaling weakened protection.","description":"Nrf2 silencing supported Nrf2 dependence of ergothioneine protection in the cisplatin ototoxicity study.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"cf22281c-8f55-5b89-8a49-a2edca7d202f","slug":"cochlear-model-nrf2-silencing","display_name":"Nrf2 silencing in the cochlear-cell experimental model","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3e9cd0e3-cb67-59f2-abb2-eefb8d9dad2a","slug":"cochlear-ergo-antioxidant-response","display_name":"Ergothioneine-associated cochlear-cell antioxidant response","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"939c92c3-50ea-5a4a-9654-8e3b94448132","slug":"ergothioneine","display_name":"L-Ergothioneine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No direct NRF2 binding demonstrated; preparation-specific node avoids assigning this silencing result to a human protein.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ergothioneine","display_name":"L-Ergothioneine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Disabling antioxidant signaling weakened protection.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"8a9d85e9-df97-53a3-8a09-6efcf0d7a575","evidence_kind":"source_excerpt","locator":"Lines 416-422","start_line":416,"end_line":422,"excerpt":"## ergothioneine-nrf2-dependence\nDisabling antioxidant signaling weakened protection.\nNrf2 silencing supported Nrf2 dependence of ergothioneine protection in the cisplatin ototoxicity study.\nModel: Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation.\nLimitations: No direct NRF2 binding demonstrated; preparation-specific node avoids assigning this silencing result to a human protein.\nEvidence access: Primary abstract\nThe Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648","model_system":"Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation.","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":"2f037d98-f3d0-5dbe-80d8-90b738f130d6","stable_key":"import-59b18080-c560-563d-abc5-bac4ee82a27c","title":"Ergothioneine: transport, redox chemistry 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":"b6def8119f03cfabeec2fb55ba924340dc612e1dd42f05404201fa2b7ced5259","revision_id":"f88c38e6-ffb5-5a68-83ca-4610ca2c2df4","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}