Beyond 7-ketocholesterol: reassessing the biological and biomarker relevance of 7β-hydroxycholesterol

A critical, albeit non-exhaustive, analysis of non-enzymatic oxysterols as biomarkers of redox imbalance and oxidative damage in human pathology challenges the prevailing view that 7-ketocholesterol (7KC) is consistently the most reliable indicator of oxidative stress and the most toxic product of free radical-mediated cholesterol oxidation. Accumulating evidence supports the combined assessment of 7β-hydroxycholesterol (7βOHC), which is consistently generated under oxidative conditions, alongside 7KC as a complementary biomarker of redox perturbation. Notably, in specific pathological contexts, 7βOHC appears to more sensitively reflect alterations in redox status than 7KC. Moreover, the cytotoxic and pro-inflammatory effects of 7βOHC are, in several disease settings, comparable to or even greater than those exerted by 7KC. In this context, the ability of 7βOHC to induce oxidative damage to cellular and tissue structures and to activate inflammatory signaling pathways underscores its significant contribution to redox-driven pathology. Collectively, these observations argue against a hierarchical classification of oxysterol toxicity and support the inclusion of 7βOHC in multiparametric approaches for the assessment of oxidative stress and oxidative damage-related disorders.