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

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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.

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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

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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.

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Authors and Affiliations

  1. Cardiovascular Research Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Vipin Kumar Verma, Salma Malik, Ekta Mutneja, Anil Kumar Sahu, Jagriti Bhatia & Dharamvir Singh Arya

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  1. Vipin Kumar Verma
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Correspondence to Dharamvir Singh Arya.

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Verma, V., Malik, S., Mutneja, E. et al. Attenuation of ROS-mediated myocardial ischemia–reperfusion injury by morin via regulation of RISK/SAPK pathways. Pharmacol. Rep 72, 877–889 (2020). https://doi.org/10.1007/s43440-019-00011-2

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