{"id":"11188339-0bc5-5012-94af-80135ce2fa17","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-side-chain-hydroxylation","predicate":"is_metabolised_by","statement":"Incubation of capsaicin with phenobarbital-induced rat liver postmitochondrial supernatant produced omega-hydroxycapsaicin, also detected in the urine of rabbits given capsaicin, and other analogs of capsaicin such as dihydrocapsaicin and nonivamide also formed similar metabolites via aliphatic hydroxylation; the polar metabolites were inactive when tested for antinociceptive activity and pungency while their parent compounds exhibited strong sensory effects, suggesting that hydroxylation of the side chain plays an important role in detoxification.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5774c62f-55c8-58e0-83e7-b93dba922602","mechanism_event_label":"Putting a hydroxyl on the tail switches the molecule off, for both heat and pain relief.","subject":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"object":{"id":"946b23d1-dede-5d60-82ed-021fd578483a","slug":"aliphatic-side-chain-hydroxylation","display_name":"Hydroxylation of the aliphatic side chain of a capsaicinoid","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5774c62f-55c8-58e0-83e7-b93dba922602","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-side-chain-hydroxylation-event","event_type":"biochemical_relationship","label":"Putting a hydroxyl on the tail switches the molecule off, for both heat and pain relief.","description":"Incubation of capsaicin with phenobarbital-induced rat liver postmitochondrial supernatant produced omega-hydroxycapsaicin, also detected in the urine of rabbits given capsaicin, and other analogs of capsaicin such as dihydrocapsaicin and nonivamide also formed similar metabolites via aliphatic hydroxylation; 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zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7c4eee5bf34dac159665170e5eca63fcbf3a5146133b9d7dc0b6ec01bda4493a\", \"start_char\": 0, \"end_char\": 1399, \"text_sha256\": \"7c4eee5bf34dac159665170e5eca63fcbf3a5146133b9d7dc0b6ec01bda4493a\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Incubation with phenobarbital-induced rat liver postmitochondrial supernatant, with rabbit urine confirmation and in vivo activity testing","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Capsaicin, dihydrocapsaicin and nonivamide incubated with an NADPH-generating system, with pentobarbital sleeping time as a readout of enzyme inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Identifies side-chain hydroxylation as a shared detoxification route and shows the products are inactive. The enzyme-inhibition arm tested capsaicin, not dihydrocapsaicin, which is recorded on that claim.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Rat and rabbit","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Putting a hydroxyl on the tail switches the molecule off, for both heat and pain relief.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dhc-p8614248] Metabolism of capsaicinoids: evidence for aliphatic hydroxylation and its pharmacological implications. (1995). https://pubmed.ncbi.nlm.nih.gov/8614248/ DOI: 10.1016/0024-3205(95)00091-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"605b790e-4b2f-5f49-b26b-b5021f6f8db4","evidence_kind":"source_excerpt","locator":"Lines 530-541","start_line":530,"end_line":541,"excerpt":"### dhc-side-chain-hydroxylation\nIncubation of capsaicin with phenobarbital-induced rat liver postmitochondrial supernatant produced omega-hydroxycapsaicin, also detected in the urine of rabbits given capsaicin, and other analogs of capsaicin such as dihydrocapsaicin and nonivamide also formed similar metabolites via aliphatic hydroxylation; the polar metabolites were inactive when tested for antinociceptive activity and pungency while their parent compounds exhibited strong sensory effects, suggesting that hydroxylation of the side chain plays an important role in detoxification.\nCondition category: normal\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: Putting a hydroxyl on the tail switches the molecule off, for both heat and pain relief.\norganism: Rat and rabbit\ntissue_or_cell_type: Liver\nexperimental_model: Incubation with phenobarbital-induced rat liver postmitochondrial supernatant, with rabbit urine confirmation and in vivo activity testing\nlimitations: Identifies side-chain hydroxylation as a shared detoxification route and shows the products are inactive. The enzyme-inhibition arm tested capsaicin, not dihydrocapsaicin, which is recorded on that claim.\nexposure: Capsaicin, dihydrocapsaicin and nonivamide incubated with an NADPH-generating system, with pentobarbital sleeping time as a readout of enzyme inhibition\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/8614248.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7c4eee5bf34dac159665170e5eca63fcbf3a5146133b9d7dc0b6ec01bda4493a\", \"start_char\": 0, \"end_char\": 1399, \"text_sha256\": \"7c4eee5bf34dac159665170e5eca63fcbf3a5146133b9d7dc0b6ec01bda4493a\"}\n[dhc-p8614248] Metabolism of capsaicinoids: evidence for aliphatic hydroxylation and its pharmacological implications. 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