Theses (MSc. Molecular Medicine)

Myocardial infarction (MI) leads to irreversible damage to cardiomyocytes via the activation of numerous cells signalling pathways. Oxidative stress and tissue death, specifically necrotic and apoptotic cardiomyocytes, initiate the inflammatory response. Previous research on the ischemic heart has shown that the stimulation of toll-like receptor 4 (TLR4) leads to an increase in the production of proinflammatory cytokines, which in turn trigger inflammatory responses, including nuclear factor-κappaB (NF-κB) as well as interleukin-6 (IL-6). Consequently, the already compromised myocardium is further damaged. Acknowledging this, many studies have been done on the marine chemical complex aaptamine as a possible therapeutic molecule for various diseases. The present investigation involved the pretreatment of Sprague-Dawley (SD) rodents along with aaptamine in low and high-dosage groups prior to the administration of isoprenaline to induce myocardial infarction. Haemodynamic measurements were recorded on the tenth day, and the heart tissues were extracted for morphological as well as immunohistochemistry investigation. There were considerable changes in heart rate and blood pressure (p<0.05). Mean arterial blood pressure (MAP) and heart rate (HR) were decreased in the high-dose aaptamine-treated group compared to the ISO group. The aaptamine was observed to effectively protect heart myocardial cells from isoprenaline-induced MI on the histopathological examination. In the aaptamine-treated group, myocardial cells exhibited a substantial decrease in the protein expressions of inflammation signalling cascade such as TLR4, NF-kB and IL-6, which were the primary focus of these experiments (p<0.05); this was in contrast to the negative control for isoprenaline-induced MI. These findings indicate that aaptamine exhibits cardioprotective effects by decreasing inflammation throughout the myocardium. Additional research is required to verify the use of other inflammatory parameters.