Protective role of alpha-phenyl-N-t-butylnitrone against ionizing radiation in U937 cells and mice.

Ionizing radiation (IR) induces the production of reactive oxygen species (ROS), which play an important causative role in radiation damage. alpha-Phenyl-N-t-butylnitrone (PBN) is one of the most widely used spin-trapping compounds for investigating the existence of free radicals in biological systems. We investigated the protective role of PBN against IR in U937 cells and mice. On exposure to IR, there was a distinct difference between the control cells and the cells pretreated with PBN in regard to viability, cellular redox status, and oxidative damage to cells. Lipid peroxidation, oxidative DNA damage, and protein oxidation were significantly lower in the cells treated with PBN when the cells were exposed to IR. Although the activities of antioxidant enzymes were comparable in PBN-treated and control cells, the [GSSG]:[GSH + GSSG] ratio and the generation of intracellular ROS were higher and the [NADPH]:[NADP(+) + NADPH] ratio was lower in control cells compared with PBN-treated cells. The IR-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of ROS, the reduction of ATP production, and the morphological change were significantly higher in control cells compared with PBN-treated cells. PBN administration for 14 days with a daily dosage of 30 mg/kg provided substantial protection against killing and oxidative damage to mice exposed to whole body irradiation. These data indicate that PBN may have great application potential as a new class of in vivo, nonsulfur-containing radiation protector.