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Investigation of therapeutic potential and molecular mechanism of vitamin P and digoxin in I/R-induced myocardial infarction in rat

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Abstract

Ischemic–reperfusion (I/R) is a major event in the pathogenesis of ischemic heart disease that leads to higher rate of mortality. The study has been designed to investigate the therapeutic potential and molecular mechanism of vitamin P and digoxin in I/R-induced myocardial infarction in isolated rat heart preparation by using Langendorff apparatus. The animals were treated with vitamin P (50 and 100 mg/kg; p.o.) and digoxin (500 μg/kg) for 5 consecutive days. Digoxin served as a positive control in the present study. On the sixth day, the heart was harvested and induced to 30 min of global ischemia followed by 120 min of reperfusion using Langendorff apparatus. The coronary effluent was collected at different time intervals (i.e. basal, 1, 15, 30, 45, 60 and 120 min.) for the assessment of myocardial contractility function. In addition, creatine kinase–M and B subunits (CK-MB), lactate dehydrogenase (LDH1) and Na+-K+-ATPase activity along with oxidative tissue biomarkers (i.e. thio-barbituric acid reactive substances (TBARS) and reduced glutathione (GSH)) changes were estimated. The I/R of myocardium produced decrease in coronary flow rate; increase in CK-MB, LDH1 and Na+-K+-ATPase activity along with increase in TBARS and decrease in GSH levels as compared to normal group. The treatment with vitamin P (100 mg/kg) and digoxin (500 μg/kg) have produced a significant (p < 0.05) ameliorative effect against I/R induced above functional, metabolic and tissue biomarkers changes. Vitamin P has an ameliorative potential against I/R induced myocardial functional changes. It may be due to its free radical scavenging and anti-infarct property via inhibition of Na+-K+-ATPase activity. Therefore, it can be used as a potential therapeutic medicine for the management of cardiovascular disorders.

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Acknowledgments

The authors are thankful to Akal Toxicology Research Centre, a unit of Akal College of Pharmacy and Technical Education, Mastuana Sahib, Sangrur-148001, Punjab (India), for supporting this study and providing technical facilities for this work.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Ethics Committee (IAEC, no.: ATRC/16/13; Dated: 16.11.2013) and the care of the animals was taken as per the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Environmental and Forest, Government of India (Reg. no. 1407/a/11/CPCSEA).

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  1. Department of Pharmacology, Cardiovascular Division, Akal Toxicology Research Centre, Akal College of Pharmacy and Technical Education, Mastuana Sahib, Sangrur, 148001, Punjab, India

    Harwinder Singh, Parneet Kaur, Pradeep Kaur, Arunachalam Muthuraman, Gurpreet Singh & Manjinder Kaur

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  1. Harwinder Singh
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Correspondence to Arunachalam Muthuraman.

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Singh, H., Kaur, P., Kaur, P. et al. Investigation of therapeutic potential and molecular mechanism of vitamin P and digoxin in I/R-induced myocardial infarction in rat. Naunyn-Schmiedeberg's Arch Pharmacol 388, 565–574 (2015). https://doi.org/10.1007/s00210-015-1103-8

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