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  3. 7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

  • Biochem Pharmacol. 2020 Mar;173:113648. doi: 10.1016/j.bcp.2019.113648.
Anne Vejux 1,  Dehbia Abed-Vieillard 2,  Khadija Hajji 3,  Amira Zarrouk 4,  John J Mackrill 5,  Shubhrima Ghosh 6,  Thomas Nury 7,  Aline Yammine 8,  Mohamed Zaibi 9,  Wafa Mihoubi 10,  Habiba Bouchab 11,  Boubker Nasser 11,  Yaël Grosjean 2,  Gérard Lizard 12
Affiliations

Affiliations

  • 1 Université de Bourgogne Franche-Comté/Inserm, Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270, 21000 Dijon, France. Electronic address: anne.vejux@u-bourgogne.fr.
  • 2 Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, UMR 6265 CNRS, UMR 1324 INRA, Université Bourgogne Franche-Comté, 21000 Dijon, France.
  • 3 University Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03, Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecules Valorisation, Tunis, Tunisia.
  • 4 Faculty of Medicine, LR12ES05, Laboratory - NAFS "Nutrition - Functional Food & Vascular Health", Monastir, & University Sousse, Faculty of Medicine, Sousse, Tunisia.
  • 5 Department of Physiology, Biosciences Institute, University College Cork, Cork, Ireland.
  • 6 Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry, Indian Institute of Technology, Delhi, New Delhi, India.
  • 7 Université de Bourgogne Franche-Comté/Inserm, Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270, 21000 Dijon, France.
  • 8 Bioactive Molecules Research Laboratory, Doctoral School of Sciences and Technologies, Faculty of Sciences, Lebanese University, Beirut 1103, Lebanon.
  • 9 Clore Laboratory, University of Buckingham, Hunter Street, Buckingham, United Kingdom.
  • 10 Centre de Biotechnologie de Sfax, Lab. Biotechnologie Moléculaire des Eucaryotes, Sfax, Tunisia.
  • 11 Laboratory of Biochemistry and Neurosciences, Department of Biology, University Hassan I, 26000 Settat, Morocco.
  • 12 Université de Bourgogne Franche-Comté/Inserm, Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270, 21000 Dijon, France. Electronic address: gerard.lizard@u-bourgogne.fr.
PMID: 31586589 DOI: 10.1016/j.bcp.2019.113648
Abstract

Oxysterols are molecules derived by the oxidation of Cholesterol and can be formed either by auto-oxidation, enzymatically or by both processes. Among the oxysterols formed by auto-oxidation, 7-ketocholesterol and 7β-hydroxycholesterol are the main forms generated. These oxysterols, formed endogenously and brought in large quantities by certain foods, have major cytotoxic properties. They are powerful inducers of oxidative stress, inducing dysfunction of organelles (mitochondria, lysosomes and peroxisomes) that can cause cell death. These molecules are often identified in increased amounts in common pathological states such as cardiovascular diseases, certain eye conditions, neurodegenerative disorders and inflammatory bowel diseases. To oppose the cytotoxic effects of these molecules, it is important to know their biological activities and the signaling pathways they affect. Numerous cell models of the vascular wall, eye, brain, and digestive tract have been used. Currently, to counter the cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol, natural molecules and oils, often associated with the Mediterranean diet, as well as synthetic molecules, have proved effective in vitro. Bioremediation approaches and the use of functionalized nanoparticles are also promising. At the moment, invertebrate and vertebrate models are mainly used to evaluate the metabolism and the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol. The most frequently used models are mice, rats and rabbits. In order to cope with the difficulty of transferring the results obtained in Animals to humans, the development of in vitro alternative methods such as organ/body-on-a-chip based on microfluidic technology are hopeful integrative approaches.

Keywords

7-Ketocholesterol; 7β-Hydroxycholesterol; Animal models; Cell models; Organ/body-on-a-chip; Oxiapoptophagy; Signaling pathways.

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