Cardioprotective Potential of Zinc and Vitamin E Against Isoprenaline-Induced Myocardial Infarction in Albino Rats by Targeting Autophagy: A Histological and Biochemical Study

Abstract

Background: Myocardial infarction (MI) is a leading cause of morbidity and mortality. It is associated with oxidative stress, apoptosis and inflammation. Zinc (Zn) and vitamin E (VE) are known to exert antioxidant and anti-inflammatory effects.Aim of the Work: Evaluate the cardioprotective potential of Zn, VE and their combination against isoprenaline (ISO)-induced myocardial infarction in adult male albino rats.Materials and Methods: Forty rats divided into five groups; I (control), II (ISO group): rats were injected subcutaneously (SC) with ISO (100 mg/kg) on the 20th and 21st days at interval of 24 h. Groups III (Zn group), IV (VE group) and V (ZE group): rats received respectively daily Zn (30 mg/kg), VE (100 mg/kg) or combination of both orally for 21 days and injected with ISO as group II. On the 22nd day, electrocardiography, biochemical and histological studies were done. Myocardial sections were subjected to HE deterioration of cardiac function with elevated cardiac enzymes, MDA, TNF-α and mTOR, in addition to reduced SOD, IL-10 and AMPK. Myocardial sections showed disturbed architecture with marked inflammatory infiltration and significantly increased caspase-3 and decreased beclin 1 immunoexpression. Groups III and IV revealed decreased cardiac enzymes, MDA, TNF-α and mTOR, in addition to elevated SOD, IL-10 and AMPK. Myocardial sections showed nearly normal histology with significantly decreased caspase-3 and increased beclin 1 immunoexpression. Group V presented the most protection with results significant to both groups III and IV.Conclusion: Combined Zn and VE pretreatment proved to have protective effect against ISO-induced MI more than using either of them alone regarding the electrocardiography, biochemical and histological parameters and this was through targeting autophagy and modulating its AMPK-mTOR pathway