title: Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.
abstract: OBJECTIVE
  One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.
  
  
  METHODS
  DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.
  
  
  RESULTS
  The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.
  
  
  CONCLUSIONS
  Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.
authors.affiliation: Stomatology Special Consultation Clinic, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, People's Republic of China; Department of Stomatology, Branch of Shanghai First People's Hospital, Shanghai, People's Republic of China.
authors.forename: Junye
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Stomatology, Branch of Shanghai First People's Hospital, Shanghai, People's Republic of China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Xu
authors.affiliation: Stomatology Special Consultation Clinic, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, People's Republic of China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D003676:Deferoxamine / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D012469:Salivary Glands / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D017262:Siderophores / Q000627:therapeutic use*
chemical_list: D017262:Siderophores; D003676:Deferoxamine