Studies on cerebral protection of digoxin against ischemia/reperfusion injury in mice

Shaminder Kaur, Ashish K. Rehni, Nirmal Singh, Amteshwar S. JAGGi

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The present study was designed to investigate the possible neuroprotective effect of digoxin induced pharmacological preconditioning (PP) and its probable mechanism. Bilateral carotid artery occlusion (BCAO) of 17 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion (I/R) induced cerebral injury in male swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using elevated plus maze test. Degree of motor incoordination was evaluated using inclined beam walking test, rota rod test and lateral push test. Digoxin (0.08 mg/kg, i.p.) was administered 24 h before surgery in a separate group of animals to induce PP. BCAO followed by reperfusion, produced significant rise in cerebral infarct size along with impairment of memory and motor coordination. Digoxin treatment produced a significant decrease in cerebral infarct size and reversal of i/R induced impairment of memory and motor incoordination. Digoxin induced neuroprotective efect was abolished significantly by verapamil (15 mg/kg, i.p.), a L-type calcium channel blocker, ruthenium red (3mg/kg, s.c.), an intracellular ryanodine receptor blocker and 3, 4-dichlorobenzamil (Na +/Ca2+ exchanger inhibitor). These findings indicate that digoxin preconditioning exerts a marked neuroprotective efect on the ischemic brain, which is possibly linked to digitalis induced increase in intracellular calcium levels eventually leading to the activation of calcium sensitive signal transduction cascades.

Original languageEnglish (US)
Pages (from-to)435-443
Number of pages9
JournalYakugaku Zasshi
Volume129
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • 3,4-dichlorobenzamil
  • Cerebral ischemia
  • Digoxin
  • Na/Ca exchanger
  • Pharmacological preconditioning
  • Ruthenium red
  • Verapamil

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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