scholarly journals A Link between Cholesterol Levels and Phenobarbital Induction of Cytochromes P450

2002 ◽  
Vol 291 (2) ◽  
pp. 378-384 ◽  
Author(s):  
Jean-Claude Ourlin ◽  
Christoph Handschin ◽  
Michel Kaufmann ◽  
Urs A. Meyer
Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 867 ◽  
Author(s):  
Alexey M. Petrov ◽  
Artem A. Astafev ◽  
Natalia Mast ◽  
Aicha Saadane ◽  
Nicole El-Darzi ◽  
...  

In mammalian retina, cholesterol excess is mainly metabolized to oxysterols by cytochromes P450 27A1 (CYP27A1) and 46A1 (CYP46A1) or removed on lipoprotein particles containing apolipoprotein E (APOE). In contrast, esterification by sterol-O-acyltransferase 1 (SOAT) plays only a minor role in this process. Accordingly, retinal cholesterol levels are unchanged in Soat1−/− mice but are increased in Cyp27a1−/−Cyp46a1−/− and Apoe−/− mice. Herein, we characterized Cyp27a1−/−Cyp46a1−/−Soat1−/− and Cyp27a1−/−Cyp46a1−/−Apoe−/− mice. In the former, retinal cholesterol levels, anatomical gross structure, and vasculature were normal, yet the electroretinographic responses were impaired. Conversely, in Cyp27a1−/−Cyp46a1−/−Apoe−/− mice, retinal cholesterol levels were increased while anatomical structure and vasculature were unaffected with only male mice showing a decrease in electroretinographic responses. Sterol profiling, qRT-PCR, proteomics, and transmission electron microscopy mapped potential compensatory mechanisms in the Cyp27a1−/−Cyp46a1−/−Soat1−/− and Cyp27a1−/−Cyp46a1−/−Apoe−/− retina. These included decreased cholesterol biosynthesis along with enhanced formation of intra- and extracellular vesicles, possibly a reserve mechanism for lowering retinal cholesterol. In addition, there was altered abundance of proteins in Cyp27a1−/−Cyp46a1−/−Soat1−/− mice that can affect photoreceptor function, survival, and retinal energy homeostasis (glucose and fatty acid metabolism). Therefore, the levels of retinal cholesterol do not seem to predict retinal abnormalities, and it is rather the network of compensatory mechanisms that appears to determine retinal phenotype.


2020 ◽  
Vol 134 (12) ◽  
pp. 1403-1432 ◽  
Author(s):  
Manal Muin Fardoun ◽  
Dina Maaliki ◽  
Nabil Halabi ◽  
Rabah Iratni ◽  
Alessandra Bitto ◽  
...  

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.


2016 ◽  
Vol 49 (03) ◽  
Author(s):  
G Schoretsanitis ◽  
S Lammertz ◽  
C Hiemke ◽  
G Janssen ◽  
G Gründer ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document