Efeito protetor do complexo de inclusão ácido úsnico/ß-ciclodextrina em coração isolado de rato submetido à lesão por isquemia e reperfusão

• Ano de defesa: 2015
• Autor(a) principal: Santos, Péligris Henrique dos
• Orientador(a): Santos, Sandra Lauton
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Sergipe
• Programa de Pós-Graduação: Pós-Graduação em Ciências Fisiológicas
• País: Brasil
• Palavras-chave em Português: Fisiologia; Infarto do miocárdio; Stress oxidativo; Antioxidantes; Reperfusão miocárdica; Isquemia; Estresse oxidativo; Líquens; Polifenóis
• Palavras-chave em Inglês: Antioxidant; Oxidative stress; Myocardial infarction; Lichens; Polyphenols
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: https://ri.ufs.br/handle/riufs/3990

The interruption of the blood supply causes a change in the cellular redox status, promotes oxidative stress, tissue damage and changes in heart function. Therefore, antioxidant compounds, such as usnic acid, can prevent these changes, since they are able to re-establish cellular redox status and preserve the tissue functions. The goal of this study was to determine whether pretreatment with inclusion complex usnic acid (UA) / β-cyclodextrin (βCD) promotes cardioprotection after ischemia and reperfusion. Initially, the characterization of inclusion complex between the AU and the βCD was performed through thermogravimetry / derivative thermogravimetry (TG / DTG), differential scanning calorimetry (DSC), spectrophotometry in the infrared (FTIR) and scanning electron microscopy (MEV). After characterization, was initiated evaluating the cardioprotective effects of the inclusion complex AU / βCD. For this, Wistar rats (250-300 g) divided into two groups: the group pretreated with 50 mg / kg / day AU / βCD and pretreated with βCD group. After the pretreatment, the heart of the animal was removed to be mounted in an isolated organ perfusion system for induction of ischemia and reperfusion and were evaluated the pressure developed in the left ventricle (LVDP), heart rate (HR) and arrhythmia severity index (ASI). Also was determined in liver and heart the amount of lactate dehydrogenase (LDH) released, the formation of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and catalase (CAT). Furthermore was verified the amount of thiol groups. The results of the physico-chemical characterization showed that UA was complexed in the cavity of βCD and may be seen in the TG weight loss in the second step, where the inclusion complex showed Δm = 19.2% while the physical mixture, Δm = 16.2%. Furthermore, it was demonstrated by SEM that the physical mixture has not interacted with βCD while the inclusion complex underwent shape change. The FTIR spectra indicated the presence of the AU in the inclusion complex in a higher proportion, in turn, the physical mixture was observed in the presence of AU lesser extent. When evaluating the cardioprotective effects of the inclusion complex AU / βCD, it was found that the pretreatment preserved LVDP (AU: 89.9% vs. 6.3 + βCD: 53.9 + 8.6%, p < 0 05) reduced the scores obtained in ASI (AU: 2.5 + 0.5 ua vs. βCD: 11.00 + 0.57 ua; p < 0.0001) and did not change the FC (AU / βCD: 78 5 + 8.6% vs βCD: 79.6 + 9.2%, p > 0.05). In biochemical assays, pretreatment reduced the amount of LDH released (AU: 0.063 + 0.026 U / L vs βCD: 0.224 + 0.036 U / L, p < 0.05) reduced the formation of MDA (AU: 5, 87 + 0.57 nmol MDA / g vs βCD: 13.02 + 1.04 nmol MDA / g, p < 0.0001), promoted the SOD activity (AU: 0.086 + 0.013 U SOD / mg protein vs. βCD: 0,050 + 0,004 U SOD / mg protein, p < 0.05) and CAT (AU: 0.054 + 0.006 ΔE / min / mg protein vs. βCD: 0.023 + 0.002 ΔE / min / mg protein; p < 0.001) and increased presence of thiol groups (AU: 97.83 + 4.23 mol / mg protein vs. βCD: 54.31 + 3.28 mol / mg protein, p < 0.0001 ). Moreover, to investigate the toxicity was not observed change in baseline levels of LDH (AU: 0.068 + 0.021 U / L vs βCD: 0.070 + 0,023U / L; p > 0.05) and MDA (AU: 8.59 + 0.27 nmol MDA / g vs βCD: 8.43 + 0.21 nmol MDA / g, p > 0.05) nor change in the SOD activity (AU: 0,025 + 0,001 U SOD / mg protein vs. βCD 0.026 + 0.001 U SOD / mg protein, p > 0.05), or CAT (AU: 0.020 + 0.004 ΔE / min / mg protein vs. βCD: 0.015 + 0.002 ΔE / min / mg protein, p > 0.05) in the liver by promoting increase of thiol groups only (AU: 245.4 + 15.6 mmol / mg protein vs. βCD: 181.8 + 14.3 mmol / mg protein , p < 0.05). Thus, it was found that the pretreatment with the inclusion complex preserved contractile function, heart protection promoted and showed no signs of toxicity.