Rizzetti Danize Aparecida, Martín Ángela, Corrales Patricia, Fernandez Francisca, Simões Maylla Ronacher, Peçanha Franck Maciel, Vassallo Dalton Valentim, Miguel Marta, Wiggers Giulia Alessandra
Cardiovascular Physiology Laboratory, Universidade Federal do Pampa, BR 472, Km 592, Uruguaiana, Rio Grande do Sul, Brazil.
Department of Basic Health Sciences, Universidad Rey Juan Carlos, Antenas s/n, Alcorcón, Spain.
Toxicol Lett. 2017 Nov 5;281:158-174. doi: 10.1016/j.toxlet.2017.10.001. Epub 2017 Oct 5.
The study aimed to investigate the effects of egg white hydrolysate (EWH) on vascular disorders induced by mercury (Hg). For this, male Wistar rats were treated for 60days: Untreated (saline, i.m.); Mercury (HgCl, i.m., 1st dose 4.6μg/kg, subsequent doses 0.07μg/kg/day); Hydrolysate (EWH, gavage, 1g/kg/day); Hydrolysate-Mercury. Systolic (SBP) and diastolic (DBP) blood pressure measurement and vascular reactivity experiments in aorta were performed. We analyzed endothelial dependent and independent vasodilator responses and vasoconstrictor response to phenylephrine (Phe) in absence and presence of endothelium, a NOS inhibitor, a NADPH oxidase inhibitor, the superoxide dismutase, a non-selective COX inhibitor, a selective COX-2 inhibitor, an AT-1 receptors blocker. In situ superoxide anion production, SOD-1, NOX-4, p22phox, COX-2 and AT-1 mRNA levels and NOX-1 protein expression were performed in aorta while the determination of angiotensin converting enzyme (ACE) activity was measured in plasma. As results, EWH prevented the increase in SBP and Phe responses and the endothelial dysfunction elicited by Hg, which was related to decreased ACE activity and NOX activation by EWH and, subsequently, alleviated ROS production and improved NO bioavailability in aorta. In conclusion, EWH could be considered as alternative or complementary treatment tools for Hg-induced cardiovascular damage.
本研究旨在探讨蛋清水解物（EWH）对汞（Hg）诱导的血管疾病的影响。为此，将雄性Wistar大鼠治疗60天：未治疗组（生理盐水，肌肉注射）；汞组（HgCl，肌肉注射，首剂4.6μg/kg，后续剂量0.07μg/kg/天）；水解物组（EWH，灌胃，1g/kg/天）；水解物-汞组。进行了收缩压（SBP）和舒张压（DBP）测量以及主动脉血管反应性实验。我们分析了在有无内皮、一氧化氮合酶（NOS）抑制剂、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂、超氧化物歧化酶、非选择性环氧化酶（COX）抑制剂、选择性COX-2抑制剂、血管紧张素Ⅱ1型受体（AT-1）阻滞剂存在的情况下，内皮依赖性和非依赖性血管舒张反应以及对去氧肾上腺素（Phe）的血管收缩反应。在主动脉中检测原位超氧阴离子生成、超氧化物歧化酶1（SOD-1）、NADPH氧化酶4（NOX-4）、p22吞噬细胞氧化酶（p22phox）、COX-2和AT-1信使核糖核酸（mRNA）水平以及NOX-1蛋白表达，同时在血浆中测定血管紧张素转换酶（ACE）活性。结果显示，EWH可预防Hg引起的SBP升高和Phe反应增加以及内皮功能障碍，这与EWH降低ACE活性和抑制NOX激活有关，随后减轻了主动脉中的活性氧（ROS）生成并改善了一氧化氮（NO）的生物利用度。总之，EWH可被视为Hg诱导的心血管损伤的替代或补充治疗工具。
