Metformin fights against radiation-induced early developmental toxicity

Abstract

Nuclear pollution intertwined accidental irradiation not only triggers acute and chronic radiation syndromes, but also endangers embryonic development in sight of uncontrollable gene mutation. Metformin (MET), a classic hypoglycemic drug, has been identified to possess multiple properties. In this study, we explored the radioprotective effects of MET on the developmental abnormalities and deformities induced by irradiation among three “star drugs”. Specifically, zebrafish (Danio rerio) embryos exposed to 5.2 Gy gamma irradiation at 4 h post fertilization (hpf) showed overt developmental toxicity, including hatching delay, hatching rate decrease, developmental indexes reduction, morphological abnormalities occurrence and motor ability decline. However, MET treatment erased the radiation-induced phenotypes. In addition, MET degraded inflammatory reaction, hinders apoptosis response, and reprograms the development-related genes expression, such as sox2, sox3, sox19a and p53, in zebrafish embryos following radiation challenge. Together, our findings provide novel insights into metformin, and underpin that metformin might be employed as a promising radioprotector for radiation-induced early developmental toxicity in pre-clinical settings.