Studies on Cerebral Protection of Digoxin against Ischemia/Reperfusion Injury in Mice
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概要
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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 17min followed by reperfusion for 24h 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 (0.08mg/kg, i.p.) was administered 24h 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 effect was abolished significantly by verapamil (15mg/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^+/Ca^<2+> exchanger inhibitor). These findings indicate that digoxin preconditioning exerts a marked neuroprotective effect 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.
- 公益社団法人日本薬学会の論文
- 2009-04-01
著者
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Jaggi Amteshwar
Department of Pharmaceutical Sciences and Drug Research, Punjabi University
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Singh Nirmal
Department of Pharmaceutical Sciences and Drug Research, Punjabi University
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Singh Nirmal
Dep. Of Pharmaceutical Sciences And Drug Res. Punjabi Univ.
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Singh Nirmal
Department Of Pharmaceutical Sciences And Drug Research Punjabi University
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Jaggi Amteshwar
Department Of Pharmaceutical Sciences And Drug Research Punjabi University
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Rehni Ashish
Chitkara College of Pharmacy
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Rehni Ashish
Chitkara College Of Pharmacy Chandigarh-patiala National Highway
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KAUR Shaminder
Department of Pharmaceutical Sciences and Drug Research, Punjabi University
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Kaur Shaminder
Department Of Pharmaceutical Sciences And Drug Research Punjabi University
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Singh Nirmal
Department Of Pharmaceutical Sciences & Drug Research Punjabi University
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