ABSTRACT
High-dose ionizing radiation-induced damage depends upon the total dose, dose-rate, modes of delivery, and surface area irradiated. High LET (linear energy transfer) radiation is more damaging than low LET radiation. In humans, bone marrow syndrome dose is 3 Gy, gastrointestinal (GI) syndrome dose is 6 Gy, and CNS syndrome doses are 50 Gy or more. Irradiation alters the expression of microRNAs that allow the translation of pro-apoptotic proteins from their respective mRNAs. Irradiation activates Nrf2 by ROS for protection. Nrf2 becomes resistant to ROS during chronic oxidative stress later on. Antioxidants activate ROS-resistant Nrf2. Individual antioxidant was administered only before irradiation despite the existence of long-lived free radicals. Oral administration of a mixture of antioxidants before and after irradiation reduced radiation damage in sheep, rabbit, and mice. Replacement therapy alone or in combination with transplantations of bone marrow improved the survival rates of lethally irradiated individuals, but all survivors of transplanted cells later die because of host versus graft rejection. A mixture of micronutrients, which would simultaneously reduce oxidative stress and inflammation by enhancing the levels of antioxidant enzymes through the activation of Nrf2/ARE pathway and dietary and endogenous antioxidants, and reduce radiation damage, is proposed.
