{"id":"edbbe0d5-465e-570d-bee8-9ea9ec54fabb","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-napqi-ascorbate","predicate":"reduces_in_assay","statement":"Ascorbic acid decreased binding through reduction of NAPQI to acetaminophen in the comparison.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3ddd2037-f543-5c1d-a2f5-6592a5644641","mechanism_event_label":"Different reductants changed the same reactive intermediate by different chemistry.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"43887d3e-e850-568f-9585-659c5561b3a7","slug":"napqi","display_name":"N-Acetyl-p-benzoquinone imine / NAPQI","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"3ddd2037-f543-5c1d-a2f5-6592a5644641","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-napqi-ascorbate-event","event_type":"biochemical_relationship","label":"Different reductants changed the same reactive intermediate by different chemistry.","description":"Ascorbic acid decreased binding through reduction of NAPQI to acetaminophen in the comparison.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"43887d3e-e850-568f-9585-659c5561b3a7","slug":"napqi","display_name":"N-Acetyl-p-benzoquinone imine / NAPQI","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glutathione-research/6424115.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\", \"start_char\": 0, \"end_char\": 1307, \"text_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Enzyme oxidation and radiolabeled binding assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"NAPQI or acetaminophen with reductants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell-free/microsomal finding; vitamin C is not established here as a clinical antidote.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Glutathione research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Mouse microsomes and cell-free cytochrome-P450 system","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Different reductants changed the same reactive intermediate by different chemistry.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Acetaminophen reactive-metabolite handling","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9456b380-04c0-505d-b79d-4989b125b2eb","evidence_kind":"source_excerpt","locator":"Lines 1061-1072","start_line":1061,"end_line":1072,"excerpt":"### glutathione-napqi-ascorbate\nAscorbic acid decreased binding through reduction of NAPQI to acetaminophen in the comparison.\nCondition category: normal\nnutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Different reductants changed the same reactive intermediate by different chemistry.\norganism: Mouse microsomes and cell-free cytochrome-P450 system\ntissue_or_cell_type: Acetaminophen reactive-metabolite handling\nexperimental_model: Enzyme oxidation and radiolabeled binding assays\nlimitations: Cell-free/microsomal finding; vitamin C is not established here as a clinical antidote.\nexposure: NAPQI or acetaminophen with reductants\nevidence_span: {\"source_cache\": \"artifacts/glutathione-research/6424115.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\", \"start_char\": 0, \"end_char\": 1307, \"text_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\"}\n[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. 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