Life Sciences & Biotechnology
Title : | Novel paradigms for the development of antioxidant-based radio-protective agent by targeting Nrf2 for ameliorating radiation-induced damages |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Tamizhselvan Gnanasekaran, K.S. Hegde Medical Academy, Karnataka |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | tamizh096@gmail.com |
Details
Executive Summary : | The harmful effects of radiation injuries to living cells are primarily due to oxidative stress. Changes in the antioxidant pathway are usually linked to inflammatory conditions, followed by tissue damage, which leads to pathological consequences. Our preliminary data on in vitro and in silico approaches using ferulic acid (FA) exhibited a significant reduction in radiation-induced DNA damages in peripheral blood. The FA (10?g/ml and 25?g/ml) was treated ex vivo human peripheral blood (n=3) for 30mins at 37?C±1?C and exposed to 1.5Gy of ?- rays of ??Co at a dose rate of 0.789Gy/min and allowed for repair an hour at 37?C±1?C. The pre-treated blood with FA showed a significant reduction in reactive oxygen species and DNA damage compared to the radiation-treated group. Further, the study was extended to reveal FA's mechanism as a potential radio-protective agent with the Keap1-Nrf2 protein-protein interaction as a cellular drug target. The FA strongly binds with Keap1-Nrf2. The binding stability observed throughout the molecular dynamic simulation with 50 ns can be explained by the higher hydrophobic nature of binding site residues of Keap1 and FA. This disruption of Keap1-Nrf2 protein-protein interaction facilitates the nuclear translocation of Nrf2 during radiation-induced oxidative stress. Thus, the present proposal would look on in silico approaches for screening FA as a better antioxidant-based radio-protectors. Quantitative data must be generated in order to get a mechanistic understanding of biological processes in vitro/in vivo. |
Co-PI: | Dr. Suchetha Kumari N, Nitte University,6th Floor, Mangaluru, Karnataka-575018, Dr. Gollapalli Pavan, Nitte University,6th Floor, Mangaluru, Karnataka-575018 |
Total Budget (INR): | 29,19,400 |
Organizations involved