{"id":"9e9b7038-482c-5daf-841d-3059a874c6df","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-cyp2e1-leaky-gut","predicate":"increases","statement":"Fructose promoted leaky gut, endotoxaemia and liver fibrosis through ethanol-inducible cytochrome P450-2E1-mediated oxidative and nitrative stress.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ffb0c19e-52e2-5cde-b08a-9e7ec0eed058","mechanism_event_label":"The enzyme alcohol stabilises is itself enough to open the gut barrier.","subject":{"id":"cab0024c-2ee0-5cdd-bc3a-d3b372868085","slug":"cyp2e1","display_name":"Human cytochrome P450 2E1","entity_type_key":"protein"},"object":{"id":"e653568c-ba57-5379-80a9-18ae320391b6","slug":"intestinal-permeability","display_name":"Intestinal permeability to macromolecules","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ffb0c19e-52e2-5cde-b08a-9e7ec0eed058","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-cyp2e1-leaky-gut-event","event_type":"biochemical_relationship","label":"The enzyme alcohol stabilises is itself enough to open the gut barrier.","description":"Fructose promoted leaky gut, endotoxaemia and liver fibrosis through ethanol-inducible cytochrome P450-2E1-mediated oxidative and nitrative stress.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3b8175a3-8dc5-5343-a49e-54af17fe4a40","slug":"liver-fibrosis","display_name":"Liver fibrosis","entity_type_key":"cellular_process"},"role":"downstream_outcome","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"517ec73b-2632-50a0-ad56-aa98869efe63","slug":"plasma-endotoxin","display_name":"Circulating endotoxin concentration","entity_type_key":"cellular_process"},"role":"downstream_measure","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"cab0024c-2ee0-5cdd-bc3a-d3b372868085","slug":"cyp2e1","display_name":"Human cytochrome P450 2E1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e653568c-ba57-5379-80a9-18ae320391b6","slug":"intestinal-permeability","display_name":"Intestinal permeability to macromolecules","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/alcohol-research/30959577.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d\", \"start_char\": 0, \"end_char\": 1961, \"text_sha256\": \"1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Fructose feeding in mice with CYP2E1 deletion and gut barrier measurement","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Fructose feeding with and without CYP2E1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Recorded because it isolates the enzyme: the leak and fibrosis required CYP2E1, which ethanol induces. The driver here is fructose, not ethanol.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ethanol","display_name":"Ethanol","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The enzyme alcohol stabilises is itself enough to open the gut barrier.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[alcohol-p30959577] Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress. (2021). https://pubmed.ncbi.nlm.nih.gov/30959577/ DOI: 10.1002/hep.30652","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestine and liver","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2f971ecd-8879-58bc-9942-c040cabc915c","evidence_kind":"source_excerpt","locator":"Lines 501-512","start_line":501,"end_line":512,"excerpt":"### alcohol-cyp2e1-leaky-gut\nFructose promoted leaky gut, endotoxaemia and liver fibrosis through ethanol-inducible cytochrome P450-2E1-mediated oxidative and nitrative stress.\nCondition category: normal\nnutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes.\nplain_language: The enzyme alcohol stabilises is itself enough to open the gut barrier.\norganism: Mouse\ntissue_or_cell_type: Intestine and liver\nexperimental_model: Fructose feeding in mice with CYP2E1 deletion and gut barrier measurement\nlimitations: Recorded because it isolates the enzyme: the leak and fibrosis required CYP2E1, which ethanol induces. The driver here is fructose, not ethanol.\nexposure: Fructose feeding with and without CYP2E1\nevidence_span: {\"source_cache\": \"artifacts/alcohol-research/30959577.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d\", \"start_char\": 0, \"end_char\": 1961, \"text_sha256\": \"1a80ad0b106d815118c6c4174ff22f9a86c4e41f549edb39e5d663c6efd7af3d\"}\n[alcohol-p30959577] Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress. (2021). https://pubmed.ncbi.nlm.nih.gov/30959577/ DOI: 10.1002/hep.30652","model_system":"Fructose feeding in mice with CYP2E1 deletion and gut barrier measurement","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [alcohol-p30959577] Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress. (2021). https://pubmed.ncbi.nlm.nih.gov/30959577/ DOI: 10.1002/hep.30652","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4b310db0-1387-548c-9e3d-6d2ed634b2cd","stable_key":"import-fcc4fa9c-4dc8-5566-b780-1a486c4d3e72","title":"Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"cb7e8dc390e8bf302cd5e230cadff6ce9847b4aad8a3691a308964d93ba59a85","revision_id":"4b344e1e-4129-579c-a058-50262b03f9a8","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}