METHOD DEVELOPMENT OF CARDIOTOXICITY STUDY AS A PART OF SAFETY ASSESSMENT OF NEW FOOD ADDITIVES

• Main Author: Mutiara Nirwana, Hana
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/56670
• Institution: Institut Teknologi Bandung

Food additives could stimulate certain biological effects when these substances enter our body. Therefore, it is necessary to ensure the safety of food additives before use. One of the safety components is the absence of toxic effect that may be caused such as cardiotoxicity. Cardiotoxicity is a side effect of several types of drugs, especially chemotherapy drugs. One of the mechanisms for the emergence of cardiotoxic effects is through the interaction of an inducing compound with the Topoisomerase II? enzyme, which is widely found in cardiomyocytes. This interaction produces an enzyme-DNA-drug complex that can induce cardiomyopathy. This research was conducted to examine the cardiotoxicity prediction results of food additives with Pred-hERG and to develop a new in silico method by molecular docking and molecular dynamics simulations. Based on the method’s development, it was found that the interaction of compounds with the complex Topoisomerase II? enzyme and DNA that causes cardiotoxicity was intercalation around the nucleosides DC11, DA12, and DG13. This method also concluded that food additives which is predicted as strong cardiotoxicity through Pred-hERG such as 9-octadecenal, 2-phenylthiophene, and ?-tocopherol, were proven safe and unable to form a cleavage complex with Topoisomerase II? and DNA.