Simvastatin attenuates radiation-induced salivary gland dysfunction in mice

Abstract

Liping Xu,* Xi Yang,* Jiayan Chen, Xiaolin Ge, Qin Qin, Hongcheng Zhu, Chi Zhang, Xinchen Sun Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Objective: Statins are widely used lipid-lowering drugs, which have pleiotropic effects, such as anti-inflammation, and vascular protection. In our study, we investigated the radioprotective potential of simvastatin (SIM) in a murine model of radiation-induced salivary gland dysfunction. Design: Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent + sham irradiation (IR) (Group I), SIM + sham IR (Group II), IR + solvent (Group III), and IR + SIM (Group IV). SIM (10 mg/kg body weight, three times per week) was administered intraperitoneally 1 week prior to IR through to the end of the experiment. Saliva and submandibular gland tissues were obtained for biochemical, morphological (hematoxylin and eosin staining and Masson’s trichrome), and Western blot analysis at 8 hours, 24 hours, and 4 weeks after head and neck IR. Results: IR caused a significant reduction of salivary secretion and amylase activity but elevation of malondialdehyde. SIM remitted the reduction of saliva secretion and restored salivary amylase activity. The protective benefits of SIM may be attributed to scavenging malondialdehyde, remitting collagen deposition, and reducing and delaying the elevation of transforming growth factor β1 expression induced by radiation. Conclusion: SIM may be clinically useful to alleviate side effects of radiotherapy on salivary gland. Keywords: simvastatin, radiation protection, submandibular gland, transforming growth factor-β1, mice

Keywords

• Simvastatin
• Radiation Protection
• Submandibular Gland
• Transforming growth factor-β1
• mice.