Bio-PeroxIL Laboratory, EA7270, University of Bourgogne & Inserm, Dijon, France.
Faculty of Medicine, Laboratory 'Nutrition, Functional Food and Vascular Health' (LR12ES05), University of Monastir, Monastir, Tunisia.
Adv Exp Med Biol. 2024;1440:437-452. doi: 10.1007/978-3-031-43883-7_21.
7-Ketocholesterol and 7β-hydroxycholesterol are most often derived from the autoxidation of cholesterol. Their quantities are often increased in the body fluids and/or diseased organs of patients with age-related diseases such as cardiovascular diseases, Alzheimer's disease, age-related macular degeneration, and sarcopenia which are frequently associated with a rupture of RedOx homeostasis leading to a high oxidative stress contributing to cell and tissue damages. On murine cells from the central nervous system (158N oligodendrocytes, microglial BV-2 cells, and neuronal N2a cells) as well as on C2C12 murine myoblasts, these two oxysterols can induce a mode of cell death which is associated with qualitative, quantitative, and functional modifications of the peroxisome. These changes can be revealed by fluorescence microscopy (apotome, confocal microscopy), transmission electron microscopy, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and gas chromatography-coupled with mass spectrometry (GC-MS). Noteworthy, several natural molecules, including ω3 fatty acids, polyphenols, and α-tocopherol, as well as several Mediterranean oils [argan and olive oils, Milk-thistle (Sylibum marianum) and Pistacia lenticus seed oils], have cytoprotective properties and attenuate 7-ketocholesterol- and 7β-hydroxycholesterol-induced peroxisomal modifications. These observations led to the concept of pexotherapy.
7-酮胆固醇和 7β-羟基胆固醇通常源自胆固醇的自动氧化。它们的数量在与年龄相关的疾病（如心血管疾病、阿尔茨海默病、年龄相关性黄斑变性和肌肉减少症）的患者的体液和/或病变器官中经常增加，这些疾病通常与 RedOx 平衡的破裂有关，导致氧化应激增加，从而导致细胞和组织损伤。在来自中枢神经系统的鼠细胞（158N 少突胶质细胞、小胶质细胞 BV-2 细胞和神经元 N2a 细胞）以及 C2C12 鼠成肌细胞上，这两种氧化固醇可以诱导细胞死亡模式，其与过氧化物酶体的定性、定量和功能修饰有关。这些变化可以通过荧光显微镜（分色，共聚焦显微镜）、透射电子显微镜、流式细胞术、定量逆转录聚合酶链反应（RT-qPCR）和气相色谱-质谱联用（GC-MS）来揭示。值得注意的是，包括ω3 脂肪酸、多酚和α-生育酚在内的几种天然分子，以及几种地中海油[阿甘和橄榄油、乳蓟（Sylibum marianum）和麻疯树籽油]，具有细胞保护特性，并减轻 7-酮胆固醇和 7β-羟基胆固醇诱导的过氧化物酶体修饰。这些观察结果导致了 pexotherapy 的概念。
