الفهرس 
Acute Myocardial InfarctionOnly 14 pages are availabe for public view
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Abstract
Acute myocardial infarction (AMI) is the major cause of death worldwide. It is an acute condition produced by an imbalance between coronary blood supply and myocardial demand due to the blockage in the coronary arteries, leading to necrosis of the myocardium. The hypoxic environment causes cardiomyocyte necrosis, initiates the cellular processes of apoptosis, and autophagy, and elicits an inflammatory response with most damage occurring close to the area of coronary occlusion. Early revascularization, pharmacotherapy, and device-based therapies are preferred to AMI patients. However, reperfusion causes activation of the complex inflammatory response and massive ROS generation that lead to irreversible damage called ischemia/reperfusion injury. Therefore, there is a huge need to explore compounds that can effectively protect against AMI via inhibition of some stages that lead to inflammation or direct blockade of the generation of ROS and RNS. The use of phytochemicals and alternative medicine has proven many advantages over synthetic compounds with fewer side effects, thus phytochemicals become a promising therapeutic strategy for the amelioration of AMI. The current study was conducted to elucidate the possible protective role of diallyl trisulfide and captopril in rats with AMI in the presence and absence of PI3K inhibitor, and to investigate the role of autophagy, apoptosis and the downstream signaling pathway of PI3K/Akt in the pathogenesis of rats. Seventy adult male albino rats were divided randomly into seven equal groups according to treatment as follows: normal control group (receiving the vehicle), AMI control group (receiving the vehicle for 12 days, then receiving 85 mg/kg ISO s.c on the day 13th and 14th with 24 h interval for induction of AMI), LY294002 group (receiving 0.3 mg/kg of LY i.p.) for 14 days, before and during AMI induction), DATS group (receiving 40 mg/kg diallyl trisulfide), CAP group (receiving 50 mg/kg captopril), DATS + LY group, and CAP + LY group with the same doses. DATS and CAP were given orally and daily for 14 days prior and during AMI induction. On the day 15th, rats were sacrificed and blood was collected from the heart. Serum was separated for analysis of cardiac biomarkers cTnI and CK-MB. Cardiac tissue was used for histopathological examination and biochemical analysis of autophagy biomarkers including p62, and LC3IIB, oxidative stress biomarkers including GSH-px, MDA and HIF-1α and for assessment of gene expression of PI3K, Akt, eNOS, and FOXO-1. AMI group showed a significant increase in cTnI and CK-MB serum level compared to control group. In addition, cardiac sections from AMI group showed extensive degeneration, inflammatory reactions, fatty degeneration, severe necrotic, atrophic and apoptotic changes of cardiomyocytes. Moreover, cardiac markers of autophagy p62, LC3IIB, MDA (marker of lipid peroxidation), HIF1-α concentration, and proapoptotic FOXO-1 gene expression were significantly elevated in AMI group compared to control group. However, cardiac GSH-px enzymatic activity, and PI3K, Akt, and eNOS gene expression were significantly decreased in AMI group compared to control group. Treatment with both DATS or CAP significantly reduced serum cTnI, and CK-MB and cardiac tissue levels of p62, LC3IIB, MDA, HIF1-α levels, and FOXO-1 gene expression were significantly reduced by both DATS and CAP pretreatment compared to AMI group. However, a significant elevation of the antioxidant GSH-px enzyme activity and upregulation of PI3K, Akt, and eNOS gene expression were observed in DATS and CAP pretreated groups compared to AMI group. The histopathological alterations of cardiac tissue in AMI group were significantly alleviated by DATS and CAP prior treatment. In addition, DATS and CAP groups’ cardiac sections showed normal architecture of cardiomyocytes, few degenerative, mild atrophic and apoptotic changes, with mild focal interstitial edematous inflammatory reaction. On the other hand, when PI3K inhibitor (LY294002) was used to explore the role of PI3K/Akt pathway in AMI pathgenesis. It reversed the action of DATS and CAP on PI3K/Akt mediators. PI3K inhibitor antagonized DATS & CAP action on PI3K, Akt, eNOS, FOXO-1 gene expression. Furthermore, DATS + LY and CAP + LY co-treatment showed significant lower levels of cTnI, CK-MB, p62, MDA, and FOXO-1 gene expression compared to LY group. Whereas, GSH-px enzymatic activity and PI3K, and Akt gene expression were increased. DATS has the ability to ameliorate oxidative stress, apoptosis and inflammation in the heart. Moreover, DATS has the potential to preserve both function and structure of the heart under ischemic conditions. DATS consumption significantly reduced edema, inflammatory process and necrotic area in heart tissues of metabolic syndrome rat models. CAP is considered a free radical scavenger owing to its terminal SH group. CAP possesses antioxidant activity which can protect cells against free radical induced tissue injury and lipid peroxidation. Moreover, CAP lowers Ang II levels in blood and tissues, thus suppressing oxidative stress, inflammation, and apoptosis.