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天然化合物预防 7-酮胆固醇引起的副作用。

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

机构信息

Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism', Lab. Bio-PeroxIL, Université de Bourgogne Franche-Comté, Dijon, France.

Lab. Biomathématique, Biochimie, Biophysique et Scientométrie, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia, Algeria.

出版信息

Crit Rev Food Sci Nutr. 2019;59(19):3179-3198. doi: 10.1080/10408398.2018.1491828. Epub 2018 Oct 16.

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.

摘要

胆固醇氧化产物,也称为氧化固醇,可以通过胆固醇的自动氧化、酶促作用或两者共同形成。在这些氧化固醇中,7-酮胆固醇(7KC)主要是在胆固醇碳 7 上发生自由基攻击时形成的。由于在患有重大疾病(心血管疾病、眼病、神经退行性疾病)、某些癌症和慢性炎症性疾病的患者的组织、血浆和/或脑脊液中发现 7KC 水平升高,因此有人怀疑 7KC 可能有助于这些疾病的发展。由于 7KC 来自饮食或内源性形成,除了在肝细胞中,其代谢效率不高或很低,因此其细胞积累会引发许多副作用,包括氧化应激、炎症和细胞死亡。为了抵消 7KC 诱导的副作用,有必要对该氧化固醇激活的代谢途径进行表征,以确定细胞保护和抗衰老保护的潜在靶点。目前,一些用于传统医学的天然化合物(生育酚、脂肪酸、多酚等)或化合物混合物(油)能够抑制 7KC 的有害影响。已鉴定的不同分子可以通过不同方式进行评估(功能性食品、重组分子、治疗诊断),以预防或治疗与 7KC 相关的疾病。

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