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J Res Clin Med. 2020;8(1): 25.
doi: 10.34172/jrcm.2020.025
  Abstract View: 154
  PDF Download: 174

Original Article

Destructive effect of digitalis overdose on blood-brain barrier in rats; an experimental study

Mehmet Nuri Kocak 1 ORCID logo, Ozgur Caglar 2* ORCID logo, Dilek Destegul 3, Kemal Alp Nalci 4, Sevilay Ozmen 5, Mehmet Dumlu Aydin 6

1 Department of Neurology, Medical Faculty, Ataturk University, Erzurum, Turkey
2 Department of Pediatric Surgery, Medical Faculty, Ataturk University, Erzurum, Turkey
3 Adana City Education and Research Hospital, Department of Anesthesiology and Reanimation, Adana, Turkey
4 Department of Pharmacology, Medical Faculty, Ataturk University, Erzurum, Turkey
5 Department of Pathology, Medical Faculty, Ataturk University, Erzurum, Turkey
6 Department Neurosurgery, Medical Faculty, Ataturk University, Erzurum, Turkey
*Corresponding Author: Ozgur Caglar MD, Ataturk University, Medical Faculty, Department of Pediatric Surgery, Erzurum, Turkey. Phone: +905054884662, E-mail: drozgurcaglar@yahoo.com

Abstract

Introduction: Cardiac glycosides are widely used in critical cardiac diseases despite their unexplained mechanisms on cardio-respiratory system and other autonomic complications within both intra-uterine and post-natal life. The aim of this study is to investigate if digitalis overdose could cause a result in such complications by a destructive effect on blood-brain barrier (BBB).

Methods: Twenty-five male Sprague Dawley rats weighing 300–350 g were divided into the following groups: control (n=5), sham (isotonic) (n=5), therapeutic dose (n=5), arrhythmogenic dose (n=5), and lethal dose (n=5). The animals were euthanized and their brains were extracted. The brains were histopathologically and immunohistochemically examined to evaluate BBB morphology in the superior temporal cortex.

Results: One animal died because of experimental procedures on the first day. Macroscopic examination of brains revealed brain edema, subarachnoid hemorrhage (SAH), and narrowed cisterns in toxic doses of digitalis-treated animals. Brain histopathological examination of these groups revealed bloody subarachnoid and cisternal spaces, cortical arteriolar vasospasm, neurodegeneration, and even peri-arteriolar neuroglial component fragmentation; these changes induced BBB destruction in the high-dose digitalis-treated animals.

Conclusion: Digitalis should not be used with overdoses if the cardio-respiratory arrhythmia is unexpectedly appearing in low doses against the possibility of defected or disrupted BBB.

Keywords: Digitalis toxicity, Blood–brain barrier, Rat brain, Digoxin
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Submitted: 01 May 2020
Accepted: 07 Jun 2020
ePublished: 12 Jul 2020
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