Preventive Effect of Metformin in Radiation-Induced Xerostomia.

Abstract

Radiation induced structural damage of salivary gland including reducing acinar cell and fibrosis. These changes result in hypofunction of salivary gland which has a significant impact on the quality of life of head and neck cancer patients who treated with radiotherapy. Nevertheless, no preventive method has been found. Metformin, a diabetes drug, has recently attracted considerable attention because it can cause tissue regeneration by anti-inflammatory action and influencing stem cells. This study examined the effects of metformin on salivary gland tissue damage caused by radiation therapy. Cultured human parotid epithelial cells are irradiated with 15 Gy of 4MV X-rays. The analysis including DNA damage, inflammatory markers and proliferation, is conducted to confirm the effect of metformin. Similarly, an in vivo mouse model is established. Histologic and functional analyses, such as salivary flow rate and lag time, are performed. The in vitro experiment revealed irradiation increased DNA damage, NF-кB, IL-6, and apoptosis with reduced proliferation. The treatment with metformin decreased the radiation-induced DNA damage and inflammation, and increased proliferation. The in vivo model also shows the same results. The group taking metformin after irradiation has preserved salivary gland parenchyma compared to irradiation only group, and the functional analysis results are comparable to the normal group. Histologic and functional analysis shows that metformin reduced radiation-induced hypofunction of salivary gland. Hence, metformin can be used to prevent radiation-induced salivary gland dysfunction.