Use este identificador para citar ou linkar para este item:
https://observatorio.fm.usp.br/handle/OPI/29388
Título: | Regression of Atherosclerotic Plaques of Cholesterol-Fed Rabbits by Combined Chemotherapy With Paclitaxel and Methotrexate Carried in Lipid Core Nanoparticles |
Autor(es): | GOMES, Fernando L. T.; MARANHAO, Raul C.; TAVARES, Elaine R.; CARVALHO, Priscila O.; HIGUCHI, Maria L.; MATTOS, Fernando R.; PITTA, Fabio G.; HATAB, Sergio A.; KALIL-FILHO, Roberto; SERRANO JR., Carlos V. |
Parte de: | JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, v.23, n.6, p.561-569, 2018 |
Resumo: | In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: -49% in LDE-PTX and -59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in -57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions. |
Aparece nas coleções: | Artigos e Materiais de Revistas Científicas - FM/MCP Artigos e Materiais de Revistas Científicas - HC/InCor Artigos e Materiais de Revistas Científicas - LIM/11 Artigos e Materiais de Revistas Científicas - LIM/31 Artigos e Materiais de Revistas Científicas - ODS/03 |
Arquivos associados a este item:
Arquivo | Descrição | Tamanho | Formato | |
---|---|---|---|---|
art_GOMES_Regression_of_Atherosclerotic_Plaques_of_CholesterolFed_Rabbits_by_2018.PDF Restricted Access | publishedVersion (English) | 1.77 MB | Adobe PDF | Visualizar/Abrir Solicitar uma cópia |
Os itens no repositório estão protegidos por copyright, com todos os direitos reservados, salvo quando é indicado o contrário.