Investigation of in vitro and in vivo radioprotection by a newly-designed thiol antioxidant, N-acetylcysteine amide (NACA)

The nuclear accidents and the threat of a terrorist nuclear attack have raised awareness that high-dose total body irradiation may occur. The systemic damage observed following irradiation is partially due to the overproduction of reactive oxygen species (ROS) which disrupt the delicate pro-oxidant/antioxidant balance of tissues leading to protein, lipid, and DNA oxidation. Thiol supplementation to maintain tissue redox balance has been studied by various researchers. Cysteine and glutathione delivery compounds have been used to protect normal cells from anti-tumor agents and radiation. N-acetyl-L-cysteine (NAC) is a well-known antioxidant which is capable of facilitating glutathione (GSH) biosynthesis and replenishing intracellular GSH under oxidatively challenging circumstances. N-acetylcysteine amide (NACA), the amide form of NAC, is a newly designed and synthesized thiol-containing compound which is believed to be more lipophilic and able to more easily cross cell membranes than NAC can. A strong antioxidant which can be administered orally, such as NACA, may play an important role in preventing radiation-induced side effects in normal tissues and the whole body during unexpected radiation accidents. Our purpose is to explore the radio-protective effects of the novel cell-permeating thiol antioxidant, NACA, and thereby to explain the mechanism that provides protection against radiation to cells and animals. Various experimental designs were set up in order to investigate the in vivo and in vitro radioprotective abilities of NACA. Our preliminary evidence indicates that NACA seems to be an ideal radioprotector, and it can modulate the radiation injury and provide protection for cells and animals against ionizing radiation. It also has the ability to modulate the intracellular supplies of cysteine (CYS) and glutathione (GSH), the most important natural antioxidants.