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 (7α-ethoxy-3β-hydroxy-5α-B-homo-6-oxacholestane-5-hydroperoxide, termed “7α-ethoxy-5-OOH”) appeared as main ozonation product. In addition to structural analysis, we confirmed the remarkable cytotoxicity of 7α-ethoxy-5-OOH toward human lung adenocarcinoma A549 cells and found that its cytotoxicity is superior to that of the commonly known autoxidized cholesterol (3β-hydroxycholest-5-ene-7-one). Hence, 7α-ethoxy-5-OOH is a toxic molecule of primary importance, arising during cholesterol ozonation in the presence of ethanol.
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Abbreviations
- CL:
-
chemiluminescence
- ESI:
-
electrospray ionization
- 7α-ethoxy-5-OOH:
-
7α-ethoxy-3β-hydroxy-5α-B-homo-6-oxacholestane-5-hydroperoxide
- FAB:
-
fast-atom bombardment mode
- 7-OOH:
-
3β-hydroxycholest-5-ene-7-hydroperoxide
- NBA:
-
m-nitrobenzyl alcohol
- TIC:
-
total ion current
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Tagiri_Endo, M., Nakagawa, K., Sugawara, T. et al. Ozonation of cholesterol in the presence of ethanol: Identification of a cytotoxic ethoxyhydroperoxide molecule. Lipids 39, 259–264 (2004). https://doi.org/10.1007/s11745-004-1228-0
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DOI: https://doi.org/10.1007/s11745-004-1228-0