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Evaluation of oxidized lipids intake in the induction of oxidative stress associated with atherosclerosis in an animal model

Grant number: 14/18697-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2014
Effective date (End): November 30, 2015
Field of knowledge:Agronomical Sciences - Food Science and Technology - Food Science
Principal Investigator:Inar Castro Erger
Grantee:Maria Carolina Gomes Kessuane de Arruda
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Studies involving cell culture, animals and humans have been extensively applied in monitoring atherosclerosis, aiming its control or regression. Among the animal models regularly used it has been observed an appropriate response to dyslipidemia and inflammation induction, but a high resistance to oxidative stress. This methodological drawback has been overcome by more aggressive interventions that present low association to human model, such as radiation exposure, application of CCl4 and genetic manipulation. Therefore, the aim of this study will be alter an animal model of reference for the development of atherosclerosis, searching for an increase of oxidative stress, beside inflammation and dyslipidemia biomarkers, mainly by chronic consumption of polyunsaturated fatty acids partially oxidized, naturally present in the diet human. Fifty LDL knockout mice (C57BL / 6) receptor were divided into 5 experimental groups. One group received regular diet containing 4% fat (CONT-), while the other four groups received a high-fat modified diet (Hyper) composed of 30% lipids. Three oxidation levels were induced in oil, representing in this study a low, moderate and high level, characterized by hydroperoxides 2.47 ± 0.02 (Hyper_L), 3.87 ± 0.04 (Hyper_M) and 4 , 69 ± 0.04 meq / L (Hyper_H) concentrations, respectively. A fifth group received the diet Hyper_L, besides the induction of diabetes by means of streptozotocin (CONT +). Linseed pre-oxidized oil used in the preparation of the diets were kept at 4oC. The pelletization of feed proportionally changed the concentration of primary and secondary markers, maintaining the difference between the three levels. After 90 days of intervention, the animals were sacrificed and blood collected by cardiac puncture for determination of lipid profile. Liver, brain, heart and adipose tissue were separated, weighed and immediately frozen in nitrogen for subsequent analysis. The following biomarkers will be determined: total cholesterol and its fractions in plasma (dyslipidemia); malondialdehyde, fatty acids, activity and expression of antioxidant enzymes in the liver tissue (oxidative stress), fatty acids in adipose tissue (oxidative stress), hepatic steatosis (inflammation) and quantification of atherosclerotic plaque in the aortic arch (atherosclerosis).

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NOGUEIRA, M. S.; KESSUANE, M. C.; LOBO LADD, A. A. B.; LOBO LADD, F. V.; COGLIATI, B.; CASTRO, I. A.. Effect of long-term ingestion of weakly oxidised flaxseed oil on biomarkers of oxidative stress in LDL-receptor knockout mice. BRITISH JOURNAL OF NUTRITION, v. 116, n. 2, p. 258-269, . (14/18697-0)

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