Biological effects of oxysterols: current status.
ABSTRACT A review of relevant literature on biological activities of oxysterols (OS) and cholesterol is presented. The data clearly demonstrate manifold biological activities, often detrimental, for OS compared with little or no such activity of a deleterious nature for cholesterol itself. Cholesterol is perhaps the single most important compound in animal tissue and, as such, it is difficult to imagine it as a toxin or hazard. In contrast, OS exhibit cytotoxicity to a wide variety of cells leading to angiotoxic and atherogenic effects; alter vascular permeability to albumin; alter prostaglandin synthesis and stimulate platelet aggregation, an important process facilitating atherosclerosis and thrombosis; alter the functionality of low density lipoprotein (LDL) receptors, possibly stimulating hypercholesterolaemia; modify cholesteryl ester accumulation in various cells, inducing foam cell formation; and enrich the LDL particle in cholesteryl esters, possibly increasing its atherogenicity. Furthermore, OS are mutagenic and carcinogenic, although some have been studied as antitumour agents based on their cytotoxic properties. Moreover, numerous studies have implicated OS in membrane and enzyme alterations that are interrelated with many of the foregoing effects. The authors find that OS deserve much more attention than cholesterol itself in terms of research activity but that unfortunately the reverse is true with regard to funding.
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ABSTRACT: Myrtle (Myrtus communis L.), a culinary spice and flavouring agent for alcoholic beverages widespread in the Mediterranean area and especially in Sardinia, contains the structurally unique oligomeric non-prenylated acylphloroglucinols, semimyrtucommulone and myrtucommulone A, whose antioxidant activity was investigated during the oxidative modification of lipid molecules implicated in the onset of cardiovascular diseases. Both acylphloroglucinols showed powerful antioxidant properties during the thermal (140 degrees C), solvent-free degradation of cholesterol. Moreover, the pre-treatment with semimyrtucommulone and myrtucommulone A significantly preserved LDL from oxidative damage induced by Cu(2+) ions at 2h of oxidation, and showed remarkable protective effect on the reduction of polyunsaturated fatty acids and cholesterol, inhibiting the increase of their oxidative products (conjugated dienes fatty acids hydroperoxides, 7beta-hydroxycholesterol, and 7-ketocholesterol). Taking into account the widespread culinary use of myrtle leaves, the results of the present work qualify the natural compounds semimyrtucommulone and myrtucommulone A as interesting dietary antioxidants with potential antiatherogenicity.Chemistry and Physics of Lipids 06/2008; 155(1):16-23. DOI:10.1016/j.chemphyslip.2008.04.005 · 2.59 Impact Factor
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ABSTRACT: It has been found that cholesterol undergoes direct electrochemical oxidation on platinum electrode in dichloromethane. Voltammetric measurements show that the process is controlled by the rate of electron transfer and the height of the oxidation peak is linear vs. concentration of cholesterol. Preparative electrolysis with separated cathodic and anodic compartments afforded dicholesteryl ether in a relatively high material yield. Depending on electrolysis conditions (composition of supporting electrolyte and electrolytic cell construction) various by-products with a 3beta-chloro, 3beta-acetoxy, or 3beta-acetylamino group were obtained.Steroids 06/2008; 73(5):543-8. DOI:10.1016/j.steroids.2008.01.014 · 2.72 Impact Factor
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ABSTRACT: Conazoles are environmental and pharmaceutical fungicides. The present study relates the toxicological effects of conazoles to alterations of gene and pathway transcription and identifies potential modes of tumorigenic action. In a companion study employing conventional toxicological bioassays (Allen et al., 2006), male CD-1 mice were fed triadimefon, propiconazole, or myclobutanil in a continuous oral-dose regimen for 4, 30, or 90 days. These conazoles were found to induce hepatomegaly, to induce high levels of hepatic pentoxyresorufin-O-dealkylase activity, to increase hepatic cell proliferation, to decrease serum cholesterol, and to increase serum triglycerides. Differentially expressed genes and pathways were identified using Affymetrix GeneChips. Gene-pathway associations were obtained from the Kyoto Encyclopedia of Genes and Genomes, Biocarta, and MetaCore compendia. The pathway profiles of each conazole were different at each time point. In general, the number of altered metabolism, signaling, and growth pathways increased with time and dose and were greatest with propiconazole. All conazoles had effects on nuclear receptors as evidenced by increased expression and enzymatic activities of a series of related cytochrome P450s (CYP). A subset of altered genes and pathways distinguished the three conazoles from each other. Triadimefon and propiconazole both altered apoptosis, cell cycle, adherens junction, calcium signaling, and EGFR signaling pathways. Triadimefon produced greater changes in cholesterol biosynthesis and retinoic acid metabolism genes and in selected signaling pathways. Propiconazole had greater effects on genes responding to oxidative stress and on the IGF/P13K/AKt/PTEN/mTor and Wnt-beta-catenin pathways. In conclusion, while triadimefon, propiconazole, and myclobutanil had similar effects in mouse liver on hepatomegaly, histology, CYP activities, cell proliferation, and serum cholesterol, genomic analyses revealed major differences in their gene expression profiles.Toxicologic Pathology 02/2006; 34(7):863-78. DOI:10.1080/01926230601047832 · 1.92 Impact Factor