Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic oxidation of
cholesterol. They are present in numerous foodstuffs and have been demonstrated to be present at increased levels in the plasma of patients with
cardiovascular diseases and in atherosclerotic lesions. Thus, their role in
lipid disorders is widely suspected, and they might also be involved in important degenerative diseases such as
Alzheimer's disease,
osteoporosis, and
age-related macular degeneration. Since
atherosclerosis is associated with the presence of apoptotic cells and with oxidative and inflammatory processes, the ability of some
oxysterols, especially
7-ketocholesterol and
7beta-hydroxycholesterol, to trigger cell death, activate
inflammation, and modulate
lipid homeostasis is being extensively studied, especially in vitro. Thus, since there are a number of essential considerations regarding the physiological/pathophysiological functions and activities of the different
oxysterols, it is important to determine their
biological activities and identify their signaling pathways, when they are used either alone or as mixtures.
Oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or none whatsoever. Moreover, a substantial accumulation of polar
lipids in cytoplasmic multilamellar structures has been observed with cytotoxic
oxysterols, suggesting that cytotoxic
oxysterols are potent inducers of phospholipidosis. This basic knowledge about
oxysterols contributes to a better understanding of the associated pathologies and may lead to new treatments and new drugs. Since
oxysterols have a number of
biological activities, and as
oxysterol-induced cell death is assumed to take part in degenerative pathologies, the present review will focus on the cytotoxic activities of these compounds, the corresponding cell death signaling pathways, and associated events (oxidation,
inflammation, and phospholipidosis).