METHOD DEVELOPMENT OF CARDIOTOXICITY STUDY AS A PART OF SAFETY ASSESSMENT OF NEW FOOD ADDITIVES
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...
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| Format: | Theses |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/56670 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | 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.
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