7-Ketocholesterol: occurrence, biological activities, and plausible remediation

Oxysterols, or cholesterol oxidation products, are potentially harmful derivatives of cholesterol arising from heat treatment in food systems and enzymatic as well as non-enzymatic processes in the body. Of these, 7-ketocholesterol (7KC) is a major oxysterol implicated in age-related diseases such as atherosclerosis, macular degeneration, neurodegenerative disorders, cancers, and some inflammatory diseases. The cytotoxic pathways of 7KC often involve typical apoptotic markers such as the production of reactive oxygen species (ROS), mitochondrial and peroxisomal dysfunction, followed by the release of cytochrome c, activation of caspase-9 followed by caspase-3, and other secondary messenger activations leading to cell death. The remedial approach should thus target either the formation, post-formation degradation, or the cell-death signaling pathways of 7KC. The current article discusses the formation of different oxysterols, with special emphasis on 7KC, its pathophysiology, and further delves into exploring different probable modalities in reducing 7KC-mediated cytotoxicity through modulating apoptosis signaling pathways, use of dietary components, and delivery of exogenous bacterial degradative enzymes. In fact, antioxidants such as flavonoids, tocopherols, terpenes, polyphenols, carotenoids, and bacterial cholesterol oxidase enzyme have been reported to be effective in reducing 7KC-mediated cytotoxicity in cell lines. Overall, a comprehensive understanding of 7KC formation, its role in disease progression, and the molecular mechanisms underlying its cytotoxicity is essential for developing effective therapeutic strategies.