Protective Role of Perillic Acid Against Radiation-Induced Oxidative Stress, Cytokine Profile, DNA Damage, and Intestinal Toxicity in Mice

The radioprotective effect of perillic acid was studied using an in vivo mouse model. Whole-body exposure of Swiss albino mice to gamma-rays (6 Gy) reduced the total white blood cell count to 1035 +/- 378 cells/mm(3) on the 9(th) day, which was significantly elevated to 2196 +/- 382 cells/mm(3) by the administration of perillic acid (50 mu moles/kg body weight, intraperitoneally) on the same day. The number of bone marrow cells and a-esterase positive cells in control animals after 11 days of irradiation was reduced to 12.5 +/- 0.8 x 10(6) cells/femur and 674 +/- 45.2 /4000 cells, respectively. In perillic acid treated animals, bone marrow cellularity was increased to 14.8 +/- 1.8 x 10(6) cells/femur and a-esterase positive cells were 941 +/- 56.5 /4000 cells, similar to normal level (935 +/- 51.4/4000 cells). Administration of perillic acid could reduce the radiation-induced elevated levels of alkaline phosphatase (ALP), glutathione-pyruvate transferase (GPT) and lipid peroxidation (LPO) in both serum and liver of irradiated animals. Perillic acid could significantly enhance the glutathione (GSH) content in liver and intestinal mucosa of irradiated animals. Histopathological analysis of small intestine also suggests that perillic acid could reduce the radiation-induced intestinal damage. The level of proinflammatory cytokines such as IL-1 beta, TNF-alpha and CRP, which were elevated during irradiation, was significantly reduced by the Perillic acid administration. Perillic acid treatment could also stimulate the production of other cytokines such as GM-CSF and IFN-gamma in animals exposed to whole-body gamma irradiation. Agarose gel electrophoresis of DNA isolated from bone marrow of mice exposed to gamma radiation showed heavy damage that was reduced by treatment with perillic acid.