Astilbin Confers Radioprotection in Lung Injury via p53-Mediated Suppression of Oxidative Damage and Apoptosis

To elucidate the molecular mechanisms by which astilbin (AST) prevents and mitigates radiation-induced lung injury (RILI) both in vivo and in vitro.

In vitro, murine-derived lung epithelial cells (TC-1) were transfected with either wild-type (WT) or mutant (Mut) p53 overexpression plasmid, and exposed to 6 Gy of radiation and subsequently treated with 50 µ g/mL AST or DMSO. Cellular assays, including Western blot, immunofluorescence, TUNEL and flow cytometry, were employed to assess expressions of acetylation p53 (Ap53), phosphorylated histone H2AX (γ-H2AX), Bax and Bcl-2, as well as apoptosis and reactive oxygen species (ROS) levels, respectively. For in vivo experiment, 12 female p53-WT and 12 female p53-homozygous knockout (KO) mice were randomly assigned to 4 groups per genotype (n=3 per group) using block randomization. p53-WT and p53-KO mice received either normal saline or AST [50 mg/(kg·d)], followed by 15 Gy whole-thorax irradiation or not. Lung injury was assessed at 6 weeks post-irradiation via hematoxylin and eosin staining and immunohistochemical (IHC) detection of p53 and Ap53.

In vitro, AST markedly reduced Ap53, ROS levels, γ-H2AX expression, and apoptosis in WT-p53 cells, whereas no noticeable protective effects were observed in Mut-p53 cells (P<0.05 or P<0.01). In vivo studies showed AST effectively mitigated RILI in p53-WT mice while exhibiting no significant effects in p53-KO mice. Additionally, IHC analysis revealed that AST decreased p53 protein and Ap53 levels in the lung tissue of p53-WT mice, but had no impact on p53-KO mice.

AST alleviates radiation-induced oxidative stress, DNA damage, and apoptosis by inhibiting Ap53.