Title:Evaluation of the Effectiveness of Dantrolene Sodium against Digoxininduced
Cardiotoxicity in Adult Rats
Volume: 22
Issue: 1
Author(s): Mahmoud Zardast, Kosar Behmanesh, Tahereh Farkhondeh*, Babak Roshanravan, Hamed Aramjoo, Michael Aschner, Saeed Samarghandian*Zahra Kiani
Affiliation:
- Department of Toxicology and Pharmacology,
School of Pharmacy, Birjand University of Medical Sciences, Birjand, Iran
- Healthy
Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
Keywords:
Dantrolene sodium, digoxin, digitalis, dantrium, cardiotoxicity, rats.
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.
