Department of Veterinary Medicine, College of Veterinary and Zootecnia, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Department of Veterinary Clinic and Surgery, College of Veterinary, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Cardiovasc Toxicol. 2020 Dec;20(6):539-547. doi: 10.1007/s12012-020-09579-1.
The aim of this study was to evaluate the comparative effects of CGs on heart physiology. Twenty-eight Wistar rats were distributed into four groups (n = 7), control group received NaCl 0.9% every 24 h for 21 days; treated groups received respectively 50 μg/kg of digoxin (DIG), ouabain (OUA) and oleandrin (OLE) every 24 h for 21 days. Serial ECGs were performed, as well as serum levels of creatinine kinase (CK), its MB fraction, troponin I (cTnI), calcium (Ca) and lactic dehydrogenase (LDH). Heart tissue was processed for histology, scanning electron microscopy and Western blot analysis for cTnI, brain natriuretic peptide (BNP), sodium potassium pump alpha-1 and alpha-2. Ventricle samples were also analyzed for thiobarbituric acid reactive substances and antioxidant enzymes (SOD, GPX, and CAT). ECGs showed decrease in QT and progressive shortening of QRS. No arrhythmias were observed. No significant differences were associated with CGs treatment and serum levels of CK, CK-MB, and cTnI. Only oleandrin increased LDH levels. Histological analysis showed degenerative changes and only oleandrin promoted moderate focal necrosis of cardiomyocytes. Scanning microscopy also confirmed the greatest effect of oleandrin, with rupture and shortening of cardiac fibers. The expression of troponin I and alpha-1 isoform were not altered, however, the protein levels of BNP and alpha-2 were higher in the groups that received oleandrin and ouabain in relation to the digoxin group. All GCs affected the production of ROS, without causing lipid peroxidation, through the activation of different antioxidant pathways. It is concluded that the administration of digoxin, ouabain, and oleandrin at 50 µg/kg for 21 days caused cardiovascular damage that represent an important limitation into its future use in heart failure and antineoplastic therapy.
这项研究的目的是评估 CGs 对心脏生理学的比较影响。将 28 只 Wistar 大鼠分为四组（n = 7），对照组每天接受 0.9%的 NaCl 治疗，共 21 天；治疗组分别每天接受 50μg/kg 的地高辛（DIG）、哇巴因（OUA）和欧夹竹桃苷（OLE）治疗，共 21 天。进行了连续心电图检查，以及血清肌酸激酶（CK）、其同工酶 MB、肌钙蛋白 I（cTnI）、钙（Ca）和乳酸脱氢酶（LDH）水平的检测。对心脏组织进行了组织学、扫描电子显微镜和肌钙蛋白 I、脑钠肽（BNP）、钠钾泵α-1 和α-2 的 Western blot 分析。还分析了心室样本的硫代巴比妥酸反应物质和抗氧化酶（SOD、GPX 和 CAT）。心电图显示 QT 缩短和 QRS 进行性缩短。未观察到心律失常。CGs 治疗与血清 CK、CK-MB 和 cTnI 水平无显著相关性。只有欧夹竹桃苷增加了 LDH 水平。组织学分析显示退行性变化，只有欧夹竹桃苷促进了心肌细胞的中度局灶性坏死。扫描显微镜还证实了欧夹竹桃苷的最大影响，导致心肌纤维断裂和缩短。肌钙蛋白 I 和α-1 同工型的表达没有改变，但与地高辛组相比，接受欧夹竹桃苷和哇巴因治疗的组的 BNP 和α-2 蛋白水平更高。所有 CGs 通过激活不同的抗氧化途径影响 ROS 的产生，而不会引起脂质过氧化。研究结论为，21 天内每天给予 50μg/kg 的地高辛、哇巴因和欧夹竹桃苷会导致心血管损伤，这是其在心力衰竭和抗肿瘤治疗中的未来应用的一个重要限制。
