Hydroxytyrosol administration enhances atherosclerotic lesion development in apo E deficient mice.
Hydroxytyrosol is a phenol found in olive oil. To verify the effect of hydroxytyrosol on the development of atherosclerosis, two groups of apo E deficient male mice on a standard chow diet were used: the control group receiving only water, and the second group an aqueous solution of hydroxytyrosol in order to provide a dose of 10 mg/kg/day to each mouse. This treatment was maintained for 10 weeks. At the moment of sacrifice, blood was drawn and heart removed. Plasma lipids, apolipoproteins and monocyte Mac-1 expression were assayed as well as aortic atherosclerotic areas in both groups. Data showed no significant changes in HDL cholesterol, paraoxonase, apolipoprotein B or triglyceride levels. However, hydroxytyrosol administration decreased apolipoprotein A-I and increased total cholesterol, atherosclerotic lesion areas and circulating monocytes expressing Mac-1. The latter was highly correlated with lesion areas (r = 0.65, P < 0.01). These results indicate that administration of hydroxytyrosol in low cholesterol diets increases atherosclerotic lesion associated with the degree of monocyte activation and remodelling of plasma lipoproteins. Our data supports the concept that phenolic-enriched products, out of the original matrix, could be not only non useful but also harmful. Our results suggest that the formulation of possible functional foods should approximate as much as possible the natural environment in which active molecules are found.
Acín
Sergio
S
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Universidad de Zaragoza.
Navarro
María A
MA
Arbonés-Mainar
José M
JM
Guillén
Natalia
N
Sarría
Alfonso J
AJ
Carnicer
Ricardo
R
Surra
Joaquín C
JC
Orman
Israel
I
Segovia
Jose C
JC
Torre
Rafael de la
Rde L
Covas
María-Isabel
MI
Fernández-Bolaños
Juan
J
Ruiz-Gutiérrez
Valentina
V
Osada
Jesús
J
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood; D001057:Apolipoproteins E / Q000172:deficiency*; D043303:Aryldialkylphosphatase / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000139:chemically induced / Q000473:pathology*; D017931:DNA Primers; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity / Q000652:urine; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D017931:DNA Primers; D016177:Macrophage-1 Antigen; D014280:Triglycerides; C005975:3,4-dihydroxyphenylethanol; D043303:Aryldialkylphosphatase; D010626:Phenylethyl Alcohol