7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19. Issue 212 (September 2021)

• Record Type: Journal Article
• Authors: Ghzaiel, Imen; Sassi, Khouloud; Zarrouk, Amira; Nury, Thomas; Ksila, Mohamed; Leoni, Valerio; Bouhaouala-Zahar, Balkiss; Hammami, Sonia; Hammami, Mohamed; Mackrill, John J.; Samadi, Mohammad; Ghrairi, Taoufik; Vejux, Anne; Lizard, Gérard
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 212(2021)
• Publication Date: 2021-09
• Subjects: Adjuvant therapies -- COVID-19 -- 7-Ketocholesterol -- Oxysterols -- SARS-CoV-2 -- Viral diseases; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2021.105939
• Languages: English
• ISSNs: 0960-0760

Abstract

Graphical abstract: Highlights: 7-Ketocholesterol is essentially formed by the auto-oxidation of cholesterol. 7-Ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. 7-Ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome. Abstract: 7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.