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In this study, the distribution and activity of reductases in rat that reduced potential cytostatic oracin to its principal metabolite 11-dihydrooracin (DHO) were investigated. The extension and stereospecificity of oracin reduction to DHO were tested in microsomal and cytosolic fractions from the liver, kidney, heart, lung and wall of small intestine, caecum and large intestine. Intestinal bacterial reduction of oracin was studied as well. The amount of DHO enantiomers was measured by HPLC with Chiralcel OD-R as chiral column. Reductive biotransformation of oracin was mostly stereospecific for (+)-DHO, but the enantiomeric ratio differed significantly among individual tissues and subcellular fractions (from 56% (+)-DHO in heart microsomes to 92% (+)-DHO in liver cytosol). Stereospecificity for (-)-DHO (60%) was observed in bacterial oracin reduction in the lumen of small intestine, caecum and large intestine. Shift of the (+)-DHO\/(-)-DHO enantiomeric ratio from 90:10 (in liver subcellular fractions) to 60:40 (in-vivo) clearly demonstrated the importance of the contribution of extrahepatic metabolism to the total biotransformation of oracin to DHO.<\/jats:p>","DOI":"10.1211\/0022357021260","type":"journal-article","created":{"date-parts":[[2003,7,17]],"date-time":"2003-07-17T23:06:21Z","timestamp":1058483181000},"page":"1003-1011","source":"Crossref","is-referenced-by-count":1,"title":["Stereospecific reduction of the original anticancer drug oracin in rat extrahepatic tissues"],"prefix":"10.1093","volume":"55","author":[{"given":"Barbora","family":"Szot\u00e1kov\u00e1","sequence":"first","affiliation":[{"name":"Department of Biochemical Sciences, Research Centre LN00B125, Faculty of Pharmacy, Charles University , Heyrovsk\u00e9ho 1203, CZ-500 05 Hradec Kr\u00e1love,","place":["Czech Republic"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenka","family":"Sk\u00e1lov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Research Centre LN00B125, Faculty of Pharmacy, Charles University , Heyrovsk\u00e9ho 1203, CZ-500 05 Hradec Kr\u00e1love,","place":["Czech Republic"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"J\u00edlek","sequence":"additional","affiliation":[{"name":"Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University , Heyrovsk\u00e9ho 1203, CZ-500 05 Hradec Kr\u00e1lov\u00e9,","place":["Czech Republic"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladim\u00edr","family":"Buchta","sequence":"additional","affiliation":[{"name":"Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University , Heyrovsk\u00e9ho 1203, CZ-500 05 Hradec Kr\u00e1lov\u00e9,","place":["Czech Republic"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladim\u00edr","family":"Ws\u00f3l","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Research Centre LN00B125, Faculty of Pharmacy, Charles University , Heyrovsk\u00e9ho 1203, CZ-500 05 Hradec Kr\u00e1love,","place":["Czech Republic"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,7,1]]},"reference":[{"key":"2024103109395179900_cit1","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/oxfordjournals.jbchem.a135612","article-title":"3 Beta-Hydroxysteroid dehydrogenase of Ruminococcus sp. from human intestinal bacteria","volume":"99","author":"Akao","year":"1986","journal-title":"J. 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