Propriedades antiaterogênicas do derivado tienilacilidrazônico LASSBio-788 em ratos wistar alimentados com dieta hipercolesterolêmica

• Ano de defesa: 2011
• Autor(a) principal: Motta, Nadia Alice Vieira da
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Programa de Pós-graduação em Ciências Médicas; Ciências Médicas
• Palavras-chave em Português: Aterosclerose; N-acilidrazonas; Dieta hipercolesterolêmica; MEDICINA; CIÊNCIAS BIOMÉDICAS; Hipercolesterolemia; Atherosclerosis; N-acylhydrazones; Hypercholesterolemic diet; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA
• Link de acesso: https://app.uff.br/riuff/handle/1/19609

Atherosclerosis is closely associated with inflammatory and immune responses. The compound LASSBio-788 is a thienylacylhydrazone derivative with antiplatelet, vasodilatory and anti-inflammatory in vitro properties. In this study we aimed to evaluate the pharmacological properties of LASSBio-788, administered chronically in rats fed a hypercholesterolemic diet and to investigate its in vivo effects. In our work we have showed that chronic treatment with LASSBio-788 reduced total cholesterol (109.1 ± 4.3 x 361.0 ± 12.8 mg / dl), triglycerides (66.1 ± 1.1 vs. 186.9 ± 17.7 mg / dl), VLDL (9.8 ± 1.1 vs. 45.0 ± 4.6 mg / dl) and LDL (63.2 ± 6.1 x 330.9 ± 9.7 mg / dl), and increase HDL serum levels, when compared with AT group. Reduced the potency of platelet agonists such as adenosine diphosphate (ADP) (EC50: 1.0 ± 0.1 mm x 0.05 ± 0.02 mM in group AT) and collagen (EC50: 4.2 ± 0.8 mg / mL x 0, 1 ± 0.02 mg / ml in group AT) which were increased in the AT group. LASSBio-788 reduced the contractile response to phenylephrine (EC50: 6.6 x 7.9 x 10-7M x 10-8M), and promote an improvement in endothelium-dependent vasodilator response (EC50: 3.2 x 10 - 8M x 1.3 x 10-6 M) when compared with AT group. LASSBio-788 inhibited the production TNF-α, ICAM-1, IL-1 and IL-6 playing an important anti-inflammatory effect. In histological analysis, the compound LASSBio-788 reduced the thickening of the aortas. Our results suggest that the compound LASSBio-788 presents a potential antiatherogenic effect in vivo, exerting lipid-lowering, antioxidant, anti-inflammatory, antiplatelet and vasodilatory properties. These actions may be due to cyclic nucleotides modulation and inhibition of TXA2 production. These effects promote the TNF-α, ICAM-1, IL-1 and IL-6 inhibition, resulting in the decrease of inflammatory responses and oxidative stress. Our results suggest that the compound LASSBio-788 represents a new multi-targeted drug candidate for the treatment of atherosclerosis