Prevention of 7-ketocholesterol-induced side effects by natural compounds

Abstract

Cholesterol oxidation products, also named oxysterols, can be formed either by cholesterol auto-oxidation, enzymatically or both. Among these oxysterols, 7-ketocholesterol (7KC) is mainly formed during radical attacks that take place on the carbon 7 of cholesterol. As increased levels of 7KC have been found in the tissues, plasma and/or cerebrospinal fluid of patients with major diseases, especially age-related diseases (cardiovascular diseases, eye diseases, neurodegenerative diseases), some cancers, and chronic inflammatory diseases, it is suspected that 7KC, could contribute to their development. Since 7KC, provided by the diet or endogenously formed, is not or little efficiently metabolized, except in hepatic cells, its cellular accumulation can trigger numerous side effects including oxidative stress, inflammation and cell death. To counteract 7KC-induced side effects, it is necessary to characterize the metabolic pathways activated by this oxysterol to identify potential targets for cytoprotection and geroprotection. Currently, several natural compounds (tocopherols, fatty acids, polyphenols, etc) or mixtures of compounds (oils) used in traditional medicine are able to inhibit the deleterious effects of 7KC. The different molecules identified could be valued in different ways (functional foods, recombinant molecules, theranostic) to prevent or treat diseases associated with 7KC.

Keywords:

• 7-ketocholesterol
• natural compounds
• cytoprotection
• geroprotection

Acknowledgements

We also thank Mrs. Suzanne Rankin for reviewing the English.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This work was supported by grants from: Univ. Bourgogne (Dijon, France), Univ. Bejaia (Bejaia, Algeria), Univ. Monastir (Monastir, Tunisia), ABASIM (Association Bourguignonne pour les Applications des Sciences de l'Information en Médecine, Dijon, France), ASSAD (Louhans, France), the Department of Neurology (Prof. Thibault Moreau, University Hospital, Dijon, France), the Action Intégrée of the Comité Mixte Inter-Universitaire Franco-Marocain (CMIFM, MA/14/310) from the PHC Volubilis/Toubkal program, the Ministère de l’Enseignement Supérieur and the Centre National Pour la Recherche Scientifique et Technique (CNRST, Morocco), the projet PPR from the (CNRST, Morocco), the Ministère des Affaires Etrangères, the Conseil Régional de Bourgogne, and the University of Bourgogne, and the PHC UTIQUE (Prof. Olfa Masmoudi-Kouki, University Tunis El Manar, Tunis, Tunisia).