AIM To investigate the protective effect of a novel nanoparticle prepared by a novel free radical scavenger, imidazole nitronyl nitroxide radical (NIT), on the myocardial tissue after ionizing radiation by regulating inflammation and oxidative stress, and its mechanism.
METHODS Nanoparticles (NPs-C4-NIT) containing NIT (C4-NIT) were prepared using solvent emulsification method. The encapsulation efficiency, drug loading capacity and particle size of the nanoparticles were measured. Male BALB/c mice were used as the research subjects, the survival rate of mice after irradiation was investigated and the blood biochemical indicators and levels of CAT, SOD, GSH-Px, MDA and LDH in the mouse heart tissue were measured. ELISA method was used to measure the levels of inflammatory cytokines in the mouse cardiac tissue and Western blotting was used to detect the expression levels of p53, Bcl-2, Bax, cleaved-caspase3, Nrf-2 and HO-1 proteins in the mouse cardiac tissue. HE staining method was used to observe the protective effect on the mouse myocardial tissue.
RESULTS The circulating metabolic time of NPs-C4-NIT nanoparticles in the mouse myocardial tissue was significantly prolonged, which significantly improved the survival rate of irradiated mice as well as the pathological damage (P<0.05) and cardiac functions induced by irradiation. The activity of antioxidant enzymes in the myocardial tissue increased and the content of lipid metabolites reduced. Meanwhile, NPs-C4-NIT significantly reduced the expression of p53 and Bax cleared caspase3 in the irradiated myocardial tissue (P<0.01) and increased the expression levels of Bcl-2, Nrf-2 and HO-1 proteins (P<0.01). The pro-inflammatory factors IL-1β and TNF-α were significantly reduced (P<0.01) and the level of anti-inflammatory factor IL-4 was increased (P<0.01).
CONCLUSION Nanoparticles NPs-C4-NIT have a significant inhibitory effect on the γ radiation induced myocardial oxidative damage in mice. NPs-C4-NIT can alleviate inflammatory reactions, inhibit cell apoptosis and exert anti ionizing radiation cardioprotective effects.