title: Underlying protective mechanism of α1-adrenoceptor activation against irradiation-induced damage in rat submandibular gland.
abstract: OBJECTIVE
  Damage to salivary gland after radiotherapy for head and neck malignant tumours can lead to irreversible oral complaints, which severely impair quality of life. The protective effect of α1-adrenoceptor activation on the salivary glands after irradiation has previously been demonstrated. However, the exact mechanism remains unclear. In this study, we investigated the underlying cytoprotective mechanism of α1-adrenoceptor activation in rat submandibular glands after irradiation.
  
  
  METHODS
  Rats were locally irradiated using a linear accelerator in the head and neck region with a dose of 20Gy. After irradiation, phenylephrine (5mg/kg) was injected intraperitoneally for 7 successive days and the submandibular glands were then collected. The antiapoptotic effect of phenylephrine on the gland was examined by TUNEL, the proliferative cellular nuclei antigen (PCNA) was determined by immunohistochemistry, and the activation of c-Jun N-terminal kinase (JNK) was detected by Western blot.
  
  
  RESULTS
  The irradiation only group showed severe atrophy, increased apoptosis, enhanced cell proliferation, and the phosphorylation of JNK was markedly increased by 26.89% (P<0.05), compared to the control. The phenylephrine-treated group, however, showed remarkably alleviated atrophy, decreased apoptosis, and further increased cell proliferation, and the phosphorylation of JNK was markedly decreased by 36.00% (P<0.05), compared to the irradiation only group.
  
  
  CONCLUSIONS
  The data showed that the underlying protective mechanism of α1-adrenoceptor activation in irradiated gland might be related to improved cell proliferation, inhibited cell apoptosis, and depressed activation of JNK. It could be helpful in protecting salivary glands against irradiation damage.
authors.affiliation: Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Dalian, Liaoning, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xiang
authors.forename: Xiu-xiu
authors.initials: XX
authors.lastname: Li
authors.forename: Fu-yin
authors.initials: FY
authors.lastname: Zhang
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D034961:Antigens, Nuclear; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects* / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D034961:Antigens, Nuclear; D010656:Phenylephrine; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Irradiation; Proliferation and apoptosis; Submandibular gland; c-Jun N-terminal kinases; α(1)-Adrenoceptor