Ozonation of cholesterol in the presence of ethanol: identification of a cytotoxic ethoxyhydroperoxide molecule.

Abstract

Cholesterol ozonation was carried out in ethanol-containing aqueous or nonaqueous solvent, and the ozonized products were analyzed by chemiluminescence detection-HPLC with on-line electrospray MS (HPLC-CL-MS) and characterized on the basis of NMR and FABMS. After the ozonolysis of cholesterol in water/ethanol (aqueous system) as well as in chloroform/ethanol (nonaqueous system), a unique ethoxyhydroperoxide molecule (7alpha-ethoxy-3beta-hydroxy-5alpha-B-homo-6-oxacholestane-5-hydroperoxide, termed "7alpha-ethoxy-5-OOH") appeared as main ozonation product. In addition to structural analysis, we confirmed the remarkable cytotoxicity of 7alpha-ethoxy-5-OOH toward human lung adenocarcinoma A549 cells and found that its cytotoxicity is superior to that of the commonly known autoxidized cholesterol (3beta-hydroxycholest-5-ene-7-one). Hence, 7alpha-ethoxy-5-OOH is a toxic molecule of primary importance, arising during cholesterol ozonation in the presence of ethanol.

• Authors: Misako Tagiri-Endo, Kiyotaka Nakagawa, Tatsuya Sugawara, Kaori Ono, Teruo Miyazawa
• Journal: Lipids (Lipids) Vol. 39 Issue 3 Pg. 259-64 (Mar 2004) ISSN: 0024-4201 [Print] United States
• PMID: 15233405 (Publication Type: Journal Article)

Chemical References

• 7alpha-ethoxy-3beta-hydroxy-5alpha-B-homo-6-oxacholestane-5-hydroperoxide
• Cholestanes
• Lipid Peroxides
• Ethanol
• Ozone
• Cholesterol

Topics

• Cell Line, Tumor
• Cell Survival
• Cholestanes (toxicity)
• Cholesterol (chemistry)
• Ethanol (chemistry)
• Humans
• Lipid Peroxides (toxicity)
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Oxidation-Reduction
• Ozone (chemistry)