Dithu Thekkekkara1, Duraiswamy Basavan1, Sudhir Chandna2, Moola Joghee Nanjan3. 1. a Departement of Pharmacognosy and Phytopharmacy , J.S.S. College of Pharmacy (Off Campus, JSS University, Mysore) , Ootacamund , India. 2. b Natural Radiation Response Mechanisums Group, Division of Radiation Biosciences , Institute of Nuclear Medicine & Allied Sciences (INMAS) , Delhi , India. 3. c TIFAC CORE HD, J.S.S. College of Pharmacy (Off Campus, JSS University, Mysore) , Ootacamund , India.
Abstract
PURPOSE: Exposure to ionizing radiation causes damage to the genomic integrity and stability of the cell. Though a large number of molecules have been studied for their radioprotective capability, no single agent is available today that meets all the requirements of a good radiprotector. In this study, we have investigated a combination of Resveratrol (RSV) and 3,3'-Diindolyl methane (DIM) for its efficacy for radioprotection. It is our hypothesis that this combination that possesses less toxicity than synthetic compounds, free radical scavenging potential, and the capacity to interfere with the several of the signaling cascades that trigger damage to cell by ionizing radiation may possess good radioprotective capability. MATERIALS AND METHODS: Mice were pre-treated with a combination of RSV and DIM and the 30-day mortality assay, endogenous antioxidant levels in intestinal mucosa, metaphase chromosomal aberrations, and micronuclei formation were assessed after exposed to ionizing radiation. RESULTS: The dose modifying factor (DRF) obtained for RSV, DIM, and the combination is 1.15, 1.17, and 1.3, respectively. Pre-treatment of mice with the combination results in significant (***p = .001) protection of the endogenous antioxidant levels, chromosomal aberrations, micronuclei formation, after exposure to ionizing radiation. CONCLUSIONS: Our findings suggest that pre-treatment with the combination of RSV and DIM protects effectively from the ionizing radiation-induced damage at the molecular, cellular, and tissue levels by counteracting both the direct and indirect effects.
PURPOSE: Exposure to ionizing radiation causes damage to the genomic integrity and stability of the cell. Though a large number of molecules have been studied for their radioprotective capability, no single agent is available today that meets all the requirements of a good radiprotector. In this study, we have investigated a combination of Resveratrol (RSV) and 3,3'-Diindolyl methane (DIM) for its efficacy for radioprotection. It is our hypothesis that this combination that possesses less toxicity than synthetic compounds, free radical scavenging potential, and the capacity to interfere with the several of the signaling cascades that trigger damage to cell by ionizing radiation may possess good radioprotective capability. MATERIALS AND METHODS:Mice were pre-treated with a combination of RSV and DIM and the 30-day mortality assay, endogenous antioxidant levels in intestinal mucosa, metaphase chromosomal aberrations, and micronuclei formation were assessed after exposed to ionizing radiation. RESULTS: The dose modifying factor (DRF) obtained for RSV, DIM, and the combination is 1.15, 1.17, and 1.3, respectively. Pre-treatment of mice with the combination results in significant (***p = .001) protection of the endogenous antioxidant levels, chromosomal aberrations, micronuclei formation, after exposure to ionizing radiation. CONCLUSIONS: Our findings suggest that pre-treatment with the combination of RSV and DIM protects effectively from the ionizing radiation-induced damage at the molecular, cellular, and tissue levels by counteracting both the direct and indirect effects.