ABSTRACT Background Radiation damage severely impacts salivary gland function and cell survival, especially in head and neck radiotherapy. Tempol (TPL), a free radical scavenger, has shown protective effects against radiation damage. This research aimed to investigate the protective effects of TPL on radiation‐induced damage in Hs917.T cells and the submandibular gland (SMG) of C57BL/6 mice, along with the mechanisms involved. Methods Human parotid fibroblasts (Hs917.T) were pre‐treated with TPL and exposed to ionizing radiation (IR). Protective effects were evaluated using MTT, clonogenic survival assays, flow cytometry, and intracellular reactive oxygen species levels. In vivo, C57BL/6 mice were pre‐treated with TPL (275 mg/kg) and exposed to 15 gray (Gy). Effects were assessed by survival rates, body weight changes, histological analysis, and TUNEL staining. Changes in apoptosis‐related markers and β‐catenin signaling pathway were analyzed, and the role of TPL was verified using the β‐catenin inhibitor XAV939. Results TPL pre‐treatment increased cell survival, reduced apoptosis, alleviated cell cycle arrest, and decreased intracellular superoxide and hydrogen peroxide levels in Hs917. T cells. In C57BL/6 mice, pre‐treatment with TPL improved survival, mitigated weight loss, reduced SMG damage, and decreased apoptosis. TPL inhibited IR‐induced apoptosis by increasing Bcl‐2 expression and decreasing Bax and caspase‐9 levels. TPL exerted anti‐apoptotic and protective effects by upregulating the expression of β‐catenin, promoting its nuclear translocation, and inhibiting its phosphorylation. These protective effects of TPL were reversed by XAV939. Conclusions TPL exerted protective effects against IR‐induced damage in Hs917.T cells and the SMG of C57BL/6 mice through activating the β‐catenin signaling pathway, inhibiting cell apoptosis, and alleviating oxidative stress.
Wáng et al. (Thu,) studied this question.