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| Description
| - Redox-silent vitamin E analogues, represented by alpha-tocopheryl succinate, are potent anti-cancer drugs with potential secondary bioactivity. We verified the hypothesis that hepatic processing of these agents determines the secondary effect. Mice were repeatedly injected with alpha-tocopheryl succinate, and their systemic and hepatic vein blood was assessed for alpha-tocopheryl succinate and its hydrolysis product, vitamin E (alpha-tocopherol). While levels of alpha-tocopherol doubled compared to control mice and alpha-tocopheryl succinate accumulated in the systemic blood, no alpha-tocopheryl succinate was detected in blood draining the liver. Hepatic processing thus endows compounds like alpha-tocopheryl succinate with a secondary, anti-oxidant/anti-inflammatory activity due to converting it to the redox-active alpha-tocopherol. Our finding epitomises a novel, general paradigm that a drug can be converted in the liver into a product that has a different beneficial bioactivity.
- Redox-silent vitamin E analogues, represented by alpha-tocopheryl succinate, are potent anti-cancer drugs with potential secondary bioactivity. We verified the hypothesis that hepatic processing of these agents determines the secondary effect. Mice were repeatedly injected with alpha-tocopheryl succinate, and their systemic and hepatic vein blood was assessed for alpha-tocopheryl succinate and its hydrolysis product, vitamin E (alpha-tocopherol). While levels of alpha-tocopherol doubled compared to control mice and alpha-tocopheryl succinate accumulated in the systemic blood, no alpha-tocopheryl succinate was detected in blood draining the liver. Hepatic processing thus endows compounds like alpha-tocopheryl succinate with a secondary, anti-oxidant/anti-inflammatory activity due to converting it to the redox-active alpha-tocopherol. Our finding epitomises a novel, general paradigm that a drug can be converted in the liver into a product that has a different beneficial bioactivity. (en)
- Redoxně umlčená analoga vitamínu E jako např. alfa-tokoferyl sukcinát představují látky se silnými protirakovinnými účinky spojenými s jejich potenciální sekundární biologickou aktivitou. Ověřovali jsme hypotézu, že zpracování těchto látek v játrech determinuje jejich sekundární účinku. Myším jsme opakovaně injikovali alfa-tokoferyl sukcinát a v jejich systémovém oběhu a krvi jaterní žíly jsme sledovali alfa-tokoferyl sukcinát a produkt jeho hydrolýzy vitamín E (alfa-tokoferol). Zatímco hladiny alfa-tokoferolu se ve srovnání s kontrolami zdvojnásobily a alfa-tokoferyl sukcinát se hromadil v systémovém oběhu, v krvi odváděné z jater nebyl nalezen žádný alfa-tokoferyl sukcinát. Zpracování látek jako alfa-tokoferyl sukcinát játry jim tedy zajišťuje sekundární, antioxidační/protizánětlivou aktivitu tím, že je převádí na redoxně aktivní alfa-tokoferol. Náš poznatek tedy razí nové, obecné paradigma, že látka může být převedena játry na produkt s odlišnou užitečnou biologickou aktivitou. (cs)
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| Title
| - Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to provitamin-to-vitamin conversion
- Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to provitamin-to-vitamin conversion (en)
- Zpracování v játrech determinuje dvojí aktivitu alfa-tokoferyl sukcinátu: nové paradigma pro změnu biologické aktivity způsobenou převedením provitamínu na vitamín (cs)
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| skos:prefLabel
| - Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to provitamin-to-vitamin conversion
- Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to provitamin-to-vitamin conversion (en)
- Zpracování v játrech determinuje dvojí aktivitu alfa-tokoferyl sukcinátu: nové paradigma pro změnu biologické aktivity způsobenou převedením provitamínu na vitamín (cs)
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| skos:notation
| - RIV/68378050:_____/05:00001255!RIV06-AV0-68378050
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| http://linked.open.../vavai/riv/strany
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/68378050:_____/05:00001255
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - vitamin E; alpha-tocopheryl succinate; hepatic processing (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
| - Biochemical and Biophysical Research Communications
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
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| http://linked.open...n/vavai/riv/zamer
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| issn
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| number of pages
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