Oxygen, oxysterols, ouabain, and ozone: a cautionary tale.

The recent account of the oxidation of tissue cholesterol by ozone created in human arterial plaques by the oxidation of water by electronically excited (singlet) dioxygen depends on the identification of the oxysterols formed and on the presumption that they are formed uniquely by ozone action. The chief oxysterols found, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al and 3beta,5-dihydroxy-5beta-B-norcholestane-6beta-carboxaldehyde, were identified as their 2,4-dinitrophenylhydrazones by chromatographic properties and a single mass spectral ion m/z 597 interpreted as [M-H](-). Conventional identification procedures for oxysterols were not conducted. Accordingly, absent other evidence, error may exist; such errors are known in the literature. Moreover, the assertion that ozone be the only oxidant that could form the 5,6-secosterol aldehyde from cholesterol is unproven. Other equally novel unproven processes can be posed. The account of biological ozone mimics prior 30-year-old reports of singlet oxygen itself in biological systems. Lest a similar history develop for biological ozone three topics of steroid oxidation are here reviewed to aid in understanding the current matter. Caution in evaluating the account of biological ozone is warranted.