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| Author(s): |
Leiko Asakura
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Saúde Pública (FSP/CIR) |
| Defense date: | 2005-04-07 |
| Examining board members: |
Eder Carlos Rocha Quintão;
Dulcineia Saes Parra Abdalla;
Nágila Raquel Teixeira Damasceno;
Angela Maggio da Fonseca
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| Advisor: | Eder Carlos Rocha Quintão |
| Field of knowledge: | Health Sciences - Medicine |
| Indexed in: | Banco de Dados Bibliográficos da USP-DEDALUS |
| Location: | Universidade de São Paulo. Biblioteca da Faculdade de Saúde Pública; FSP/612.397; 17 |
| Abstract | |
Objective. Because of their structural similarities isoflavones and estrogens may to the sarne extent influence the development of experimental atherosclerosis, an hypothesis investigated in female mice partially expressing genes for LDL receptors and cholesteryl ester transfer protein (CETP). Methods. Mice were ooforectomized at eight weeks of age and thereafter submitted to a fat/cholesterol rich diet for nineteen weeks eliciting moderate hypercholesterolemia and a lipoprotein profile similar that of humans and separated in four experimental groups: subcutaneous pellet graft of 17β-ethinyl-estradiol (EE - 6μg/d, n=29); diet added mixtures of low dose (Iso Low- 27.2 mg/100g, n=25), or high dose of isoflavone mixtures (Iso High - 53.5mg/100g, n=28); and the atherogenic diet alone as a Control group (n=28). Results. After sacrifice it was shown that in spite of the lower non-HDL-C plasma concentration (mean mg/dL) reached by the EE group (84 ± 8), when compareci to the Iso Low group (95 ± 6), although not differing from the other groups, EE aortic root lesion area (mean μm2 x 103) (22.0 ± 19.5) was greater than that of Iso High (7.4 ± 6.4), from that of the Iso Low (12.3 ± 9.9) and the Control groups (10.7 ± 12.8), whereas the latter did not differ from both isoflavone treated groups. After pooling all isoflavone treated animais, their mean aortic lesion area (9.9 ± 8.6) remained lower than that of EE, not differing from that of the Control group. ln addition, the percent distribution of the number of animais with larger lesion area in reference to the aortic fat storage median area value of the Controls (8.1) was significantly different, as follow: EE>Iso Low>Iso High. Therefore, 17β-ethinyl-estradiol elicited the largest and Iso High the lowest proportion of animais with large lesion areas. This 17β-ethinylestradiol unfavorable effect might be ascribed to high autoantibodies titers against both the plasma ox-LDL (measured by optical density at 450nm) that were 0.86 in EE as compared to 0.61 in Controls, as well as against apoB-D (an oxidized fraction of LDL) that were 0.84 in EE as compared to 0.68 in Iso Low, 0.67 in Iso High, and 0.61 in Controls. In additional experiments with Control mice as the reference value (100%), in vitro mouse peritoneal uptake of donor human 1α,2α,(n)-[3H]-cholesteryl oleyl ether acetylated LDL was low in Iso High (68%), which was also lower than in Iso Low (85% ). Furthermore, the in vitro percent removal by donor human HDL of [4-14C]cholesterol from macrophages previously enriched with human [4-14C]-cholesteryl oleate acetylated LDL was enhanced in Iso High (150%), that was also greater than in Iso Low (99% ). Conclusions. Therefore, in spite of their antiatherogenic actions regarding the metabolism of cholesterol in macrophages shown in vitro, isoflavones failed to prevent against the fat fed induced atherosclerosis. It contrasts with the proatherogenic state of 17β-ethinyl-estradiol likely attributed to a pro-oxidant condition in vivo. (AU) | |