Antioxidant Probucol Reduces Mortality in Mice Exposed to Lethal Doses of Ionizing Radiation

Radiation has beneficial medical and industrial applications; however, high-dose exposure during accidents can result in severe outcomes, including fatal bone marrow failure. Total-body irradiation (TBI) of 6-10 Gy induces hematopoietic failure, primarily due to oxidative stress caused by excessive reactive oxygen species. This study aimed to evaluate the protective potential of probucol, a potent antioxidant, against lethal ionizing radiation-induced damage. Eight-week-old mice received 8 Gy TBI. Two probucol treatment strategies were tested: pretreatment, in which the drug was administered daily for 4 days before irradiation, and post-treatment, in which the drug was administered 4 h after irradiation and continued for 4 days. Survival rates, peripheral blood cell counts, bone marrow and spleen morphology, and urinary excretion levels of 8-hydroxy-2'-deoxyguanosine (oxidative DNA damage) were analyzed. Probucol pretreatment improved survival in mice that received 8 Gy TBI, whereas most of the mice in the post-treatment group and all of the mice in vehicle control group died within 30 days after exposure. Probucol pretreatments also significantly decreased the urinary excretion of 8-hydroxy-2'-deoxyguanosine compared with untreated control mice. Although TBI caused pancytopenia in both groups, peripheral blood cell counts showed no difference between the groups on day 14 postirradiation. Probucol pretreatment preserved nucleated bone marrow cells and showed extramedullary hematopoiesis in the spleen. These findings suggest that probucol pretreatment exert beneficial effects by mitigating radiation-induced bone marrow suppression and promoting compensatory extramedullary hematopoiesis within the spleen through its antioxidative action.