Evaluation of the Effectiveness of Dantrolene Sodium against Digoxininduced Cardiotoxicity in Adult Rats.

Q2 Medicine

Cardiovascular and Hematological Agents in Medicinal Chemistry Pub Date : 2023-01-01 DOI:10.2174/1871525721666230125091826

Mahmoud Zardast, Kosar Behmanesh, Tahereh Farkhondeh, Babak Roshanravan, Hamed Aramjoo, Michael Aschner, Saeed Samarghandian, Zahra Kiani

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Abstract

Background: Digoxin poisoning commonly occurs in people treated with digoxin. It has been suggested that treatment with dantrolene may be a suitable strategy for digoxin-induced cardiotoxicity.

Objective: The aim of this study was to evaluate the protective effect of dantrolene on digoxininduced cardiotoxicity in male rats.

Methods: This study was approved by the ethics committee of Birjand University of Medical Sciences (Ethical number: IR.BUMS.REC.1400.067). Forty-two Wistar rats weighing between 300- 350 gr were randomly allocated to 7 groups (n = 6) as follows: Normal Saline (NS) group, Normal Saline + Ethanol (NS + ETOH) group, Normal Saline + dantrolene 10 mg/kg (NS + Dan 10) group, Digoxin (Dig) group), Digoxin + dantrolene 5 mg/kg (Dig + Dan 5) group, Digoxin + dantrolene 10 mg/kg (Dig + Dan 10) group, Digoxin + dantrolene 20 mg/kg (Dig + Dan 20) group, Dig was injected intravenously at 12 mL / h (0.25 mg / mL). Dan (5, 10 and 20 mg/kg) was injected intravenously at 5-8 min/mL. After 1 hour, blood samples were obtained from the animals' cavernous sinus and each animal's heartremoved. The blood sample was rapidly centrifuged at 2,500 rpm for 10 minutes and the serum was separated for measurement of creatine phosphokinase (CPK), potassium (K), sodium (Na), calcium (Ca), and magnesium (Mg). The samples were stored at -20°C. The heart samples were fixed in formalin 10% for histopathological evaluation.

Results: K levels slightly increased in the dig group versus the NS group. A significant increase in the K levels was observed in the Dig + Dan 20 group versus the NS group (p < 0.001). Dig slightly decreased Ca levels in the treated group versus the NS group. The levels of Ca significantly increased in the Dig + Dan 10 group versus the Dig group (p < 0.05). Histological examination of the heart tissue in the dig group showed cardiomyocyte degeneration, increased edematous intramuscular space associated with hemorrhage, and congestion. Focal inflammatory cell accumulation in the heart tissue was also seen. Cardiomyocytes were clear and arranged in good order in the Dig + Dan 10 group.

Conclusion: dantrolene (10 mg/kg) was cardioprotective in a model of digoxin-induced cardiotoxicity, secondary to cardiac remodeling and hyperkalemia. However, further research is necessary to determine dantrolene's cardioprotective and cardiotoxic doses in animal models.

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评估丹曲林钠对成年大鼠地高辛所致心脏毒性的疗效

背景：地高辛中毒通常发生在接受地高辛治疗的患者身上。有研究表明，使用丹曲林治疗地高辛引起的心脏毒性可能是一种合适的策略：本研究旨在评估丹曲林对雄性大鼠地高辛诱导的心脏毒性的保护作用：本研究已获得比尔詹德医科大学伦理委员会批准（伦理编号：IR.BUMS.REC.1400.067）。42只体重在300-350克之间的Wistar大鼠被随机分配到以下7组（n=6）：正常生理盐水（NS）组、正常生理盐水 + 乙醇（NS + ETOH）组、正常生理盐水 + 丹曲林 10 mg/kg （NS + 丹 10）组、地高辛（Dig）组、地高辛 + 丹曲林 5 mg/kg （Dig + 丹 5）组、地高辛 + 丹曲林 10 mg/kg （Dig + 丹 10）组、地高辛 + 丹曲林 20 mg/kg （Dig + 丹 20）组，Dig 以 12 mL / h 的速度静脉注射（0.25 毫克/毫升）。丹（5、10 和 20 毫克/千克）以 5-8 分钟/毫升的速度静脉注射。1 小时后，从动物的海绵窦采集血样，并取出每只动物的心脏。血液样本在 2,500 rpm 转速下快速离心 10 分钟，分离血清，以测定肌酸磷酸激酶（CPK）、钾（K）、钠（Na）、钙（Ca）和镁（Mg）。样本保存在零下 20 摄氏度。将心脏样本固定在 10%的福尔马林中进行组织病理学评估：结果：与 NS 组相比，Dig 组的 K 含量略有增加。与 NS 组相比，Dig + Dan 20 组的 K 含量明显增加（p <；0.001）。Dig + Dan 10组与Dig组相比，Ca水平明显升高（p < 0.05）。对 Dig 组心脏组织的组织学检查显示，心肌细胞变性，水肿的肌内间隙增大，伴有出血和充血。心脏组织中还可见局部炎性细胞聚集。结论：丹曲林（10 毫克/千克）在地高辛诱导的心脏毒性模型中具有心脏保护作用，继发于心脏重塑和高钾血症。然而，要确定丹曲林在动物模型中的心脏保护和心脏毒性剂量，还需要进一步的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular and Hematological Agents in Medicinal Chemistry Medicine-Cardiology and Cardiovascular Medicine

CiteScore

2.70

自引率

0.00%

发文量

期刊介绍： Cardiovascular & Hematological Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Cardiovascular & Hematological Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Cardiovascular & Hematological medicinal chemistry. Cardiovascular & Hematological Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cardiovascular & hematological drug discovery.