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Attenuation of ROS-mediated myocardial ischemia–reperfusion injury by morin via regulation of RISK/SAPK pathways

  • Vipin Kumar Verma
  • Salma Malik
  • Ekta Mutneja
  • Anil Kumar Sahu
  • Jagriti Bhatia
  • Dharamvir Singh AryaEmail author
Article
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Abstract

Background

Oxidative stress plays an important role in the pathogenesis of myocardial ischemia–reperfusion (IR) injury. Morin, a bioflavonoid, has demonstrated antioxidant, anti-inflammatory and other diverse pharmacological activities in various experimental models such as isoproterenol-induced myocardial injury, doxorubicin-induced cardiotoxicity and neurotoxicity, as well as cisplatin-induced nephrotoxicity. Thus, this study aimed to evaluate the effect of morin in myocardial IR injury model and its underlying mechanisms.

Method

To accomplish this, male albino Wistar rats were pre-treated with morin (40 and 80 mg/kg; po) for 28 days and on 29th day, rats experienced 45-min myocardial ischemia followed by 60-min reperfusion.

Results

In comparison to IR-control group, morin pre-treatment significantly normalized hemodynamic parameters, restored antioxidant status, improved pathological changes, reduced the release of cardiac injury markers, inhibited inflammation (TNF-α/IL-6/NFκB/IKKβ) and apoptosis (increased Bcl-2, decreased Bax/Caspase-3 and TUNEL positivity) in the myocardium. This improvement in antioxidant, inflammation and anti-apoptosis markers could be due to downregulation of SAPK (p38/JNK) pathway and upregulation of survival kinase, i.e. RISK pathway (ERK/eNOS) in the myocardium.

Conclusion

Thus, morin attenuated myocardial IR injury in rats by regulation of RISK/SAPK pathways.

Graphic abstract

Keywords

Ischemia–reperfusion Morin MAPK Akt/eNOS 

Abbreviations

Akt

Protein kinase A

CK-MB

Creatinine kinase-MB

CAT

Catalase

eNOS

Endothelial nitric oxide synthase

ERK 1/2

Extracellular regulated kinase 1/2

GSH

Reduced glutathione

HR

Heart rate

IL-6

Interlukin-6

IR

Ischemia–reperfusion

JNK

c-Jun N-terminal kinase

LADCA

Left anterior descending coronary artery

LDH

Lactate dehydrogenase

LVEDP

Left ventricular end diastolic pressure

MAP

Mean arterial pressure

MAPK

Mitogen-activated protein kinase

MDA

Malondialdehyde

MI

Myocardial infarction

NF-κB

Nuclear factor-kappa B

PI3K

Phosphotidylinositol 3-kinase

RISK

Reperfusion-induced salvage kinase

SAPK

Stress-activated protein kinase

SOD

Superoxide dismutase

TNF-α

Tumour necrosis factor-α

Notes

Acknowledgements

All authors are grateful to the technical staff for their support. First author is obliged to DST-SERB, India (PDF/2016/003885) for providing fellowship and financial assistance to conduct the study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Maj Institute of Pharmacology Polish Academy of Sciences 2020

Authors and Affiliations

  1. 1.Cardiovascular Research Laboratory, Department of PharmacologyAll India Institute of Medical SciencesNew DelhiIndia

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