7-ketocholesterol: effects on viral infections and hypothetical contribution in COVID-19.

Fiche publication


Date publication

juin 2021

Journal

The Journal of steroid biochemistry and molecular biology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr LIZARD Gérard


Tous les auteurs :
Ghzaiel I, Sassi K, Zarrouk A, Nury T, Ksila M, Leoni V, Bouhaouala-Zahar B, Hammami S, Hammami M, Mackrill JJ, Samadi M, Ghrairi T, Vejux A, Lizard G

Résumé

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.

Mots clés

7-ketocholesterol, COVID-19, SARS-CoV-2, adjuvant therapies, oxysterols, viral diseases

Référence

J Steroid Biochem Mol Biol. 2021 Jun 9;:105939