title: Histamine prevents functional and morphological alterations of submandibular glands induced by ionising radiation.
abstract: OBJECTIVE
  Xerostomia is a common, disturbing side-effect among patients treated with radiotherapy for head-and-neck cancer. The aim of the present work was to investigate whether histamine could prevent salivary gland dysfunction and histological alterations exerted by ionising radiation.
  
  
  METHODS
  Forty-eight rats were divided into four groups. Histamine and histamine-5 Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5 Gy and untreated-5 Gy groups were irradiated with a single dose of whole-body Cesium-137 irradiation. Control and untreated-5 Gy groups were given daily saline injections. Three days post irradiation metacholine-induced salivary secretion was measured or animals were sacrificed and submandibular gland (SMG) removed, stained and histological characteristics were evaluated. Proliferation and apoptosis markers were studied by immunohistochemistry.
  
  
  RESULTS
  Radiation decreased salivary secretion by 40% in comparison to untreated rats, which was associated with loss of SMG mass, alteration of epithelial architecture, partial loss of secretor granular material, diminished proliferation and a remarkable apoptotic response. In contrast, histamine completely reversed the reduced salivation induced by radiation, conserved glandular mass with normal appearance and preserved the structural organisation of secretor granules. Radiation-induced toxicity is prevented by histamine essentially by suppressing apoptosis of ductal and acinar cells, reducing the number of apoptotic cells per field (19.0 ± 3.8 vs. 106.0 ± 12.0 in untreated animals, P < 0.001), and also by preventing the radiation-induced decrease in cell proliferation.
  
  
  CONCLUSIONS
  Histamine prevents morphological and functional radiation-induced damage on SMG, representing a potential radioprotector for treatment of patients undergoing radiotherapy for head and neck malignancies.
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Vanina A
authors.initials: VA
authors.lastname: Medina
authors.forename: Juan P
authors.initials: JP
authors.lastname: Prestifilippo
authors.forename: Maximo
authors.initials: M
authors.lastname: Croci
authors.forename: Eliana
authors.initials: E
authors.lastname: Carabajal
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Bergoc
authors.forename: Juan C
authors.initials: JC
authors.lastname: Elverdin
authors.forename: Elena S
authors.initials: ES
authors.lastname: Rivera
mesh_terms: D000818:Animals; D017209:Apoptosis; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006632:Histamine / Q000378:metabolism*; D008297:Male; D011832:Radiation Injuries / Q000473:pathology; D011839:Radiation, Ionizing; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012469:Salivary Glands / Q000187:drug effects / Q000528:radiation effects; D013363:Submandibular Gland / Q000187:drug effects* / Q000528:radiation effects*; D014987:Xerostomia / Q000209:etiology* / Q000517:prevention & control
chemical_list: D006632:Histamine