Administration of a novel β-hydroxybutyrate ester after radiation exposure suppresses in vitro lethality and chromosome damage, attenuates bone marrow suppression in vivo

Cellular mechanisms to protect against and repair radiation damage depend on reducing equivalents from oxidative metabolism. Two recent studies explored compounds (ex. Ex-Rad and TP-508) with efficacy in preventing injury or reducing its severity but neither takes advantage of cellular metabolism to this end. We report for the first time that a novel ketone body ester (KE) protects against injury and death in cells and animals exposed to several types of radiation. The unique metabolism of ketone bodies shifts biochemical set points, particularly of the NADP/H system which is essential to cellular antioxidant function and oxidative damage repair. Additionally, the demonstrated activity of the ketone bodies as histone deacetylase inhibitors and enhancers of DNA repair may make these compounds uniquely suited to combat radiation injury. We show that addition of KE to culture media provides significant protection to cultured osteoblasts against γ-radiation lethality when administered before or after radiatio...