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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 55  |  Page : 227-236

Prophylactic treatment with icariin prevents isoproterenol-induced myocardial oxidative stress via nuclear Factor-Like 2 activation


1 Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
2 Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

Correspondence Address:
Syed Ehtaishamul Haque
Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi - 110 062
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_469_17

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Introduction: Icariin, a major component of Epimedium species and a mild phosphodiesterase 5 (PDE-5) inhibitor, was evaluated for the prevention of myocardial oxidative stress in isoproterenol (ISO)-challenged Wistar rats. Objective: This study aimed to evaluate the cardioprotective action of icariin in ISO-intoxicated rats. Materials and Methods: Rats were daily treated with icariin (1, 5, and 10 mg/kg, p.o.) and sildenafil (0.7 mg/kg, i.p.) for 15 days. Oxidative stress was induced by subcutaneous administration of ISO (85 mg/kg s.c) in two consecutive doses at an interval of 24 h on 14th and 15th day of the study. After induction, rats were anesthetized for recording the electrocardiogram (ECG) and then sacrificed to perform immunohistochemistry and biochemical assays of heart tissue. Results: ISO treatment resulted in a marked increase in lipid peroxidation, serum markers (lactate dehydrogenase [LDH], creatine kinase-MB [CK-MB], and C-reactive protein [CRP]), and infarct size and a significant decrease in the level of reduced glutathione (GSH) and endogenous antioxidant enzymes in the myocardium. Lowering of arterial blood pressure and alteration in ECG showed significant alteration in cardiac hemodynamics. Hematoxylin and eosin staining of the cardiac tissue showed considerable myocardial damage. Pretreatment with icariin (5 and 10 mg/kg, p.o.) and sildenafil (0.7 mg/kg, i.p) significantly decreased the elevated lipid peroxidation, LDH, CK-MB, and CRP. Moreover, the results also showed an increase in endogenous antioxidants and protein expression of nuclear factor-like 2 (Nrf-2) when compared to the ISO-treated group. Conclusion: The results indicated that icariin significantly ameliorates the ISO-induced oxidative stress and restores membrane integrity and cellular damage. Thus, we can conclude that the activation of Nrf-2 signaling and PDE-5 inhibition by icariin is possibly responsible for the cardioprotection. Abbreviations used: Nrf-2: Nuclear factor-like 2, PDE-5: Phosphodiesterase-5, ISO: Isoproterenol, TCM: Traditional Chinese Medicine, ECG: Electrocardiogram, LDH: Lactate dehydrogenase, CK-MB: Creatine kinase-MB, CRP: C-reactive protein, GSH: Endogenous glutathione, TBARS: Thiobarbituric acid reactive substances, GPx: Glutathione peroxidase, GR: Glutathione reductase, GST: Glutathione-S-transferase, SOD: Superoxide dismutase, CAT: Catalase, H and E: Hemotoxylin and eosin, MAPK: Mitogen-activated protein kinase, CPCSEA: Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines, DMSO: Dimethyl sulfoxide, MM-GBSA: Molecular mechanics-generalized born surface area, BPM: Beats per minute.


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