{"id":"dd40d93a-ea66-555f-bd0b-b10b0a5fb688","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-delta-acid-platelet-txb2","predicate":"reduces-production-of","statement":"Delta-tocopherol-13′-carboxychromanol reduced A23187-stimulated TXB2 output from washed rat platelets, with the metabolite experiments reporting IC50 values in the 1.5–2.5 µM range.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"6c64bb8b-baf4-5c8e-9c4d-41208417cf60","mechanism_event_label":"The metabolite reduced a measured marker of thromboxane production in isolated rat platelets.","subject":{"id":"692528ac-5680-5d1e-bf48-d8ffd17cb97e","slug":"delta-13-carboxychromanol","display_name":"Delta-tocopherol-13′-carboxychromanol","entity_type_key":"small_molecule"},"object":{"id":"3b200ef2-893f-5ca7-93f4-ea657577a760","slug":"thromboxane-b2","display_name":"Thromboxane B2","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"6c64bb8b-baf4-5c8e-9c4d-41208417cf60","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-delta-acid-platelet-txb2-event","event_type":"biochemical_relationship","label":"The metabolite reduced a measured marker of thromboxane production in isolated rat platelets.","description":"Delta-tocopherol-13′-carboxychromanol reduced A23187-stimulated TXB2 output from washed rat platelets, with the metabolite experiments reporting IC50 values in the 1.5–2.5 µM range.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"39f9446f-52a6-502d-b507-91137726f82c","slug":"arachidonic-acid","display_name":"AA","entity_type_key":"small_molecule"},"role":"thromboxane precursor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"added activating ion","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"692528ac-5680-5d1e-bf48-d8ffd17cb97e","slug":"delta-13-carboxychromanol","display_name":"Delta-tocopherol-13′-carboxychromanol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3b200ef2-893f-5ca7-93f4-ea657577a760","slug":"thromboxane-b2","display_name":"Thromboxane B2","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Washed rat platelet stimulation and TXB2 enzyme immunoassay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"25 min compound preincubation at 37°C; 1–2 µM A23187 with 1–2 mM CaCl2 for 10 min.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"TXB2 is a stable surrogate for TXA2 production; neither clinical bleeding nor platelet aggregation was measured in this endpoint. Isolated rat platelets do not establish human antithrombotic benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Rattus norvegicus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The metabolite reduced a measured marker of thromboxane production in isolated rat platelets.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Isolated blood platelets","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d660f812-bccb-5787-aa25-2f3b7b39d136","evidence_kind":"source_excerpt","locator":"Lines 1076-1087","start_line":1076,"end_line":1087,"excerpt":"### e-sig-delta-acid-platelet-txb2\nDelta-tocopherol-13′-carboxychromanol reduced A23187-stimulated TXB2 output from washed rat platelets, with the metabolite experiments reporting IC50 values in the 1.5–2.5 µM range.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The metabolite reduced a measured marker of thromboxane production in isolated rat platelets.\norganism: Rattus norvegicus\ntissue_or_cell_type: Isolated blood platelets\nexperimental_model: Washed rat platelet stimulation and TXB2 enzyme immunoassay\nlimitations: TXB2 is a stable surrogate for TXA2 production; neither clinical bleeding nor platelet aggregation was measured in this endpoint. Isolated rat platelets do not establish human antithrombotic benefit.\nexposure: 25 min compound preincubation at 37°C; 1–2 µM A23187 with 1–2 mM CaCl2 for 10 min.\ncross_nutrient: false\n[park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884","model_system":"Washed rat platelet stimulation and TXB2 enzyme immunoassay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. 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