Oxysterols, age-related-diseases and nutritherapy: Focus on 7-ketocholesterol and 7β-hydroxycholesterol
Anne Véjux, Imen Ghzaiel, John J. Mackrill, Irundika H.K. Dias, Leila Rezig, Mohamed Ksila, Amira Zarrouk, Thomas Nury, Fatiha Brahmi, Adil El Midaoui, Smail Meziane, Atanas G. Atanasov, S. Hammami, Norbert Latruffe, P. Jouanny, Gérard Lizard
Abstract
Age-related diseases are often associated with a disruption of RedOx balance that can lead to lipid peroxidation with the formation of oxysterols, especially those oxidized on carbon-7: 7-ketocholesterol (also known as 7-oxo-cholesterol) and 7β-hydroxycholesterol. Like cholesterol, these oxysterols have 27 carbons, they are composed of a sterane nucleus and have a hydroxyl function in position 3. The oxysterols 7-ketocholesterol and 7β-hydroxycholesterol are mainly formed by cholesterol autoxidation and are biomarkers of oxidative stress. These two oxysterols are frequently found at increased levels in the biological fluids (plasma, cerebrospinal fluid), tissues and/or organs (arterial wall, retina, brain) of patients with age-related diseases, especially cardiovascular diseases, neurodegenerative diseases (mainly Alzheimer's disease), ocular diseases (cataract, age-related macular degeneration), and sarcopenia. Depending on the cell type considered, 7-ketocholesterol and 7β-hydroxycholesterol induce either caspase- dependent or -independent types of cell death associated with mitochondrial and peroxisomal dysfunctions, autophagy and oxidative stress. The caspase dependent type of cell death associated with oxidative stress and autophagy is defined as oxiapoptophagy. These two oxysterols are also inducers of inflammation. These biological features associated with the toxicity of 7-ketocholesterol, and 7β-hydroxycholesterol are often observed in patients with age-related diseases, suggesting an involvement of these oxysterols in the pathophysiology of these disorders. The cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol are counteracted on different cell models by representative nutrients of the Mediterranean diet: ω3 and ω9 fatty acids, polyphenols, and tocopherols. There are also evidences, mainly in cardiovascular diseases, of the benefits of α-tocopherol and phenolic compounds. These in vitro and in vivo observations on 7-ketocholesterol and 7β-hydroxycholesterol, which are frequently increased in age-related diseases, reinforce the interest of nutritherapeutic treatments to prevent and/or cure age-related diseases currently without effective therapies.