Curcumin nanoparticles alleviate brain mitochondrial dysfunction and cellular senescence in γ-irradiated rats

Despite the diverse applications of γ radiation in radiotherapy, industrial processes, and sterilization, it causes hazardous effects on living organisms, such as cellular senescence, persistent cell cycle arrest, and mitochondrial dysfunction. This study evaluated the efficacy of curcumin nanoparticles (CNPs) in mitigating mitochondrial dysfunction and cellular senescence induced by γ radiation in rat brain tissues. Four groups of male Wistar albino rats (n = 8 per group) were included: (Gr1) the control group; (Gr2) the CNPs group (healthy rats receiving oral administration of curcumin nanoparticles at a dose of 10 mg/kg/day, three times per week for eight weeks); (Gr3) the irradiated group (rats exposed to a single dose of 10 Gy head γ irradiation); and (Gr4) the irradiated + CNPs group (irradiated rats treated with CNPs). The data obtained demonstrated that oral administration of CNPs for eight weeks attenuated oxidative stress in γ-irradiated rats by lowering the brain's lipid peroxidation level [malondialdehyde (MDA)] and enhancing antioxidant markers [superoxide dismutase (SOD), reduced glutathione (GSH), and total antioxidant capacity (TAC)] (P < 0.05). In addition, CNPs significantly increased mitochondrial function by improving complex I, complex II, and ATP production levels compared to the irradiated group. In irradiated rats, CNPs also showed anti-neuroinflammatory effects by reducing brain interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-ĸB) levels (P < 0.05). Moreover, CNPs administered to irradiated rats significantly reduced brain β-galactosidase activity and the expression levels of p53, p21, and p16 genes (P < 0.05) while concurrently inducing a significant increase in AMPK mRNA expression compared to the irradiated group. In conclusion, CNPs ameliorated the neurotoxicity of γ radiation and hold promise as a novel agent to delay cellular senescence via their combined antioxidant, anti-inflammatory, and mitochondrial-enhancing properties.