In vivo interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol, potential surrogate markers for oxidative stress.
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.
Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, SE-141 86 Stockholm, Sweden.
Hanna
H
Larsson
Ylva
Y
Böttiger
Luigi
L
Iuliano
Ulf
U
Diczfalusy
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006262:Health; D006801:Humans; D006888:Hydroxycholesterols / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D007262:Infusions, Intravenous; D007653:Ketocholesterols / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
D015415:Biomarkers; D006888:Hydroxycholesterols; D007653:Ketocholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C003001:7-ketocholesterol