Title : Drug Repositioning For Myocardial Infarction: Computational And Pharmacological Approach
Abstract:
Myocardial Infarction (MI) related to cardiovascular diseases has been a major cause of death worldwide making it a challenge for the scientists to focus towards the protection of heart. The concept of Drug Repurposing showed Alpha-2 and Beta-1 adrenergic receptors having potent binding affinity with Tretinoin.Thus the aim of this study is to elucidate cardio-protective effect of Tretinoin in rats.
In-silico Molecular Docking and Dynamics studies were carried to analyse the binding affinity and stable interaction of drug-receptor complex.
The rats were randomized in 5 groups. MI was induced in rats using 85mg/kg Isoproterenol (ISO) twice at an interval of 24 hrs through subcutaneous route to all the groups expect normal control. The grouping of animals as follows; Normal group, positive control group (ISO), Standard group (ISO + Ascorbic acid (250 mg/kg b.w.), Low dose group (ISO + Tretinoin 5 mg/kg b.w.)& high dose group (ISO + Tretinoin 10 mg/kg b.w.). After 21 days of the study period, ECG, cardiac biomarkers and Histopathological study of heart was assessed.
Molecular Docking and Dynamics Studies have shown better drug binding affinity with Alpha-2(-9.1) and Beta-1 (-8.7) adrenergic receptors. Myocardial Infarction was developed in rats by administering Isoproterenol. Pre-treatment with Tretinoin (5 &10 mg/kg p.o.) ameliorates the myocardial lesions and decrease the levels of biomarker such as CKMB, LDH, SGPT, ALP to enhance the functioning of heart. The alteration in ECG recordings and histopathology of heart were also studied. The histopathological studies of heart treated with Tretinoin also showed recovery of destructive myocardium tissues and develops the normal architecture of heart. This provides an additional support to prove repurposing of the cardiac functions.
The present study focuses on the effective cardioprotective approach of Tretinoin towards Alpha-2 and Beta-1 adrenergic receptors binding having stable interaction along with significant decrease in cardiac biomarker levels leading to improve cardiac functions.
What will audience learn from your presentation?
- This study aimed to explore the cardioprotective activity of the repurposed drug Tretinoin
- Tretinoin as a cardioprotective drug showed effective treatment in reduction in the symptoms
- of cardiovascular diseases
- Tretinoin is a medication used to treat acne and sun-damaged skin, this same drug we can use for myocardial infarction also through its repurposing mechanism