Radiation Protection by 6-Palmitoyl Ascorbic Acid-2-Glucoside: Studies on DNA Damage in vitro, ex vivo, in vivo and Oxidative Stress in vivo

Abstract

A palmitoyl derivative of ascorbic acid 2-glucoside, 6-palmitoyl ascorbic acid-2-glucoside (PAsAG), which possess good antioxidant properties, is examined for radioprotection in vitro, ex vivo and in vivo models. PAsAG protected plasmid DNA from gamma-radiation induced damages under in vitro conditions. Presence of 1.6 mM PAsAG inhibited the disappearance of ccc (covalently closed circular) form of plasmid pBR322 with a dose modifying factor of 1.5. Comet assay studies on mouse spleen cells exposed to 6 Gy gamma-radiation (ex vivo) in presence and absence of PAsAG revealed that cellular DNA was effectively protected by this compound from radiation induced damages. Oral administration of 80 mg/kg body weight of PAsAG to mice 1 hour prior to 6 Gy whole body gamma-radiation exposure, efficiently protected cellular DNA in tissues such as spleen, bone marrow and blood, from radiation induced damages as indicated by alkaline comet assay. Oxidative stress in tissues such as liver and brain of mice, following whole body exposure to various doses of gamma-radiation (2-8 Gy), monitored as levels of GSH and peroxidation of lipids, were found considerably reduced when PAsAG was orally administered (80 mg/kg body weight) to the mice one hour prior to the radiation exposure. PAsAG administration improved the per cent survival of mice following exposure to 10 Gy whole body gamma-radiation. Thus PAsAG could act as a radioprotector under in vitro, ex vivo and in vivo conditions of ionizing-radiation exposure.