Ameliorative Effects Of Lisinopril On Biochemical, Molecular and Histopathological Changes In Experimentally-Induced Cardiac Infarction In Rats

In many nations around the world, cardiovascular illnesses diseases remain the most common reason of mortality for the general public. Clinically asymptomatic, myocardial infarction (MI) can occur before or alongside signs of heart failure (HF). Because particular therapy performed at this time might successfully postpone the real start of HF, early detection of MI is critical. This study examined the impact of lisinopril (ZestrilTM) on isoproterenol-induced myocardial infarction in rats.Method: Animals were divided into 3 groups. Group I (n=15); Normal control group. Diseased Group II (n=15); Isoproterenol was administered subcutaneously to rats (20 mg/kg/day). Treated Group III (n=15); Isoproterenol (ISO) was administered subcutaneously to rats (20 mg/kg/day) and then administrated orally with Lisinopril (LSP) daily (1mg/kg.bw) for 30 days. Parameters Creatin Kinase-MB (CK-MB), Lactate dehydrogenase (LDH), pro-B-type natriuretic peptide (pro-BNP), Troponin-T (trop-T), Myoglobin, hs-C reactive protein (hs-CRP), Tumor Necrosis Factor Alpha (TNF-α) and Interleukine-6 (IL-6) were measured in the three groups using ELISA method. Also, through using the technique of real-time Quantitative PCR, the expression level of Matrix Metalloproteinase-9 (MMP-9), Hypoxia inducible factor-1-alpha (hif1-α) and sirtuin-1 (Sirt-1) were measured in the three groups. Additionally, Histological examination was carried out in the heart tissue in all groups. Results: The findings showed that rats with MI caused by isoproterenol had significantly higher blood levels of CK-MB, LDH, pro-BNP, trop-T, myoglobin, hs-CRP, TNF-α, and IL-6 in diseased group II contrasted with Normal control group I. Also, Cardiac tissue of isoproterenol-‌induced MI rats in group II indicated significant up-regulation in MMP-9 and hif1-α gene expression levels contrasted with Normal control group I (P<0.05). Conversely, significant down-regulation in Sirt-1 expression level in diseased group II in contrasted to normal control group I. Various histopathological alterations were detected in heart tissue of rats treated with isoproterenol in diseased group II as opposed to normal control group I. Interestingly, rats treated with LSP in Treated group III demonstrated marked reduction (P<0.05) in all measured biological parameters CK-MB, LDH, pro-BNP, trop-T, myoglobin, hs-CRP, IL-6 and TNF-α II in contrasted to diseased group II. Additionally, treated group III indicated significant down-regulation in MMP-9 and hif1-α gene expression levels compared to diseased group II (P<0.05). Conversely, significant up-regulation in Sirt-1 expression level in treated group III contrasted with diseased group II. Also, heart tissue showed improvement in pathological alterations in LSP treated group III in comparison to isoproterenol rats in Diseased group II. Conclusion: These findings suggest that, supplementation of lisinopril counteracts the negative effects of ISO, and improve cardiac work.