Modulation of FOXO1/NF-κB signaling via inositol alleviates the radiation-induced brain injury

Background: The hazards emerging in the setting of ionizing radiation exposure emphasize a potential clinical predicament, and many protective trials have been challenged, compromising the mitigation of such complications. The present study elucidated the role of inositol (INS) in modifying the brain cytotoxicity induced by acute exposure to radiation.Methods: In male Wister rats, brain cytotoxicity was triggered by an acute single dose (6 Gy) of IRR, while administration of INS (30 mg/kg) before IRR or both before and after exposure. On day eight, the animals were sacrificed, and brain tissues were collected for evaluation of histological changes, oxidative stress, and inflammatory responses by estimation of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), nitrite (NOx) contents, and myeloperoxidase (MPO) activity. Also, Forkhead box protein O1 (FOXO1) and nuclear factor kappa B (NF-κB) levels were evaluated by ELISA technique.Results: Inositol exerted protection against gamma radiation as indicated by reduced tissue contents of either TBARS or NOx, with a significant increase in GSH levels, accompanied by a decrease in MPO activity and an improvement in histological alternation. These findings were interestingly observed upon pre- and post-administration of INS compared to its pre-administration for only three days. The overall molecular impact of radiation on damaging the brain tissue could be explained by modifying the expressions of the upregulated FOXO1 and NF-κB proteins. Conclusion: Here, we revealed that the anticipated adverse reaction to brain tissue in course of irradiation could be effectively protected by daily pre- and post-administration of INS supplement.