Polysaccharide From Laminaria Japonica Attenuates Radiation-Induced Xerostomia In Mice Via Activation of Nrf2 Signaling Pathway

Abstract

Background：Xerostomia is one of the most common complications during radiotherapy for head and neck cancer patients that seriously affects their quality of life. However, optimal treatment for radiation-induced xerostomia is currently unavailable. Therefore, this study aimed to investigate the protective effects of Laminaria Japonica Polysaccharide (LJP) on radiation-induced xerostomia and decipher its underlying mechanism in mice.Methods：Male eight-week-old mice were randomly divided into four groups：normal control group, LJP control group, irradiation group, and irradiation with LJP treatment group. LJP (40mg/kg) was intraperitoneally injected at 1 day before irradiation once daily for consecutive 5 days．The mice irradiated received a single radiation dose of 15Gy. Body weight, daily food and water intake were measured at 28 days post irradiation. Oxidative stress parameters (ROS and MDA) and antioxidant enzyme (MnSOD) in submandibular glands (SMG) were also assessed post irradiation. In addition, histopathology, function and weight of SMG were detected after irradiation. The expressions of Nrf2 pathway-related genes (Nrf2, HO-1 and NQO1) were measured using immunofluorescence or immunohistochemical staining and real-time PCR method. Results：Compared with the control group, irradiated mice showed increases in the levels of oxidative stress parameters (ROS and MDA), water intake and expression levels of Nrf2 pathway-related genes (Nrf2, HO-1, and NQO1), and decreases in body weight, food intake, saliva flow. Nevertheless, LJP treatment significantly increased body weights, food intake, and saliva flow in irradiated mice, markedly downregulated oxidative stress levels, improved the morphology and structure of SMG, and further promote expressions of Nrf2 pathway-related genes.Conclusion: LJP treatment alleviated radiation-induced SMG oxidative stress injury through activating Nrf2 signaling pathway, implying that LJP might be a novel agent for treating radioactive xerostomia in the future.