Tetrahedral framework nucleic acids alleviate irradiation-induced salivary gland damage.

ABSTRACT

In this study, we investigated the role of tetrahedral framework nucleic acids (tFNAs) in irradiation-induced salivary gland damage in vitro and in vivo. Irradiation-damaged submandibular gland cells (SMGCs) were treated with different concentrations of tFNAs. Cell activity was measured by CCK-8 assay. Cell death was detected by Calcein-AM/PI double staining. Cell apoptosis was assessed by flow cytometry. The expression of apoptosis proteins and inflammatory cytokines were detected by western blot. Body weight, drinking volume, saliva flow rate and lag time was measured 8 weeks after irradiation. Micromorphological changes of submandibular gland were assessed by haematoxylin-eosin and masson staining. Cell proliferation, apoptosis and microvessel density of submandibular gland were evaluated by immunohistochemical staining. tFNAs could promote cell proliferation, inhibit cell apoptosis of irradiation-damaged SMGCs and reduce irradiation induced cell death. Mechanism studies revealed that tFNAs inhibited cell apoptosis through regulating the Bcl-2/Bax/Caspase-3 signalling pathway and inhibited the release of TNF-α, IL-1ß and IL-6 to reduce cell damage caused by inflammation. Animal experiments showed that tFNAs could alleviate irradiation-induced weight loss, increased water intake, decreased saliva production and prolonged salivation lag time and could ameliorate salivary gland damage. tFNAs have a positive effect on alleviating irradiation-induced salivary gland damage and might be a promising agent for the treatment of this disease.