In vitro Studying of Deferasirox Side effects on the Structure and the Function of Bovine Liver Catalase

Oral chelators such as deferasirox are used to treat iron overload caused by blood transfusion. Considering the significant role of liver in detoxification and drug metabolism as well as the importance of catalase as a key enzyme in detoxification، this study was performed to evaluate the effect of deferasirox، which is an iron chelator on the structure and the synthesis of the bovine liver catalase. In this experimental study، the alterations in catalase activity were measured in the absence and the presence of different concentrations of deferasirox by using spectrophotometer (UV-Visible). Moreover، we used fluorescence spectroscopic methods for investigating the changes in three dimensional structure of enzyme and its function based on the changes in intrinsic emission. The data were analyzed by Excel software. Analyzing the synthesis of the enzyme showed that increased drug concentrations lead to decrease in the enzyme activity and consequently inhibition of catalase enzymatic reaction. In addition، fluorescence data represented the significant decreasing in intrinsic emission of enzyme in the presence of drug، which indicates that significant changes have been done at three dimensional environments around the enzyme chromophores. Analyzing the fluorescence quenching data at different room and physiologic temperatures was represented two binding sites for deferasirox on liver catalase enzyme. Above results suggest that deferasirox، as a chelator drug، can bind to the catalase active site then leading to functional changes of enzyme by inactivation of it، which results in side effects of this drug in liver and liver failure.