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In vivo interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol, potential surrogate markers for oxidative stress.

Abstract
The oxysterols 7beta-hydroxycholesterol and 7-ketocholesterol are cholesterol autoxidation products. These two oxysterols are formed as a result of low density lipoprotein oxidation and in a study on biomarkers for oxidative stress in patients with atherosclerosis, 7beta-hydroxycholesterol was found to be the strongest predictor of progression of carotid atherosclerosis. Interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol in vitro has been reported recently, using recombinant 11beta-hydroxysteroid dehydrogenase or rodent liver microsomes. In this study deuterium-labeled 7beta-hydroxycholesterol or 7-ketocholesterol was administered intravenously to two healthy volunteers and blood samples were collected at different time points. The mean half-life for elimination of 7beta-hydroxycholesterol from the circulation was estimated to be 1.9 h. The corresponding half-life for 7-ketocholesterol was estimated to be 1.5 h. Infusion of deuterium-labeled 7-ketocholesterol resulted in labeling of 7beta-hydroxycholesterol and vice versa. In addition, the biological within-day and between-day variations of the two oxysterols were determined. In summary, the present investigation clearly shows an interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol in humans.
AuthorsHanna Larsson, Ylva Böttiger, Luigi Iuliano, Ulf Diczfalusy
JournalFree radical biology & medicine (Free Radic Biol Med) Vol. 43 Issue 5 Pg. 695-701 (Sep 01 2007) ISSN: 0891-5849 [Print] United States
PMID17664133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Hydroxycholesterols
  • Ketocholesterols
  • cholest-5-en-3 beta,7 alpha-diol
  • 7-ketocholesterol
Topics
  • Adult
  • Biomarkers (blood)
  • Female
  • Health
  • Humans
  • Hydroxycholesterols (administration & dosage, blood, pharmacology)
  • Infusions, Intravenous
  • Ketocholesterols (administration & dosage, blood, pharmacology)
  • Male
  • Middle Aged
  • Oxidative Stress

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