Histamine prevents functional and morphological alterations of submandibular glands exerted by ionising radiation

MEDINA VA; PRESTIFILIPPO JP; CROCI M; CARABAJAL E; BERGOC RM; ELVERDIN JC; RIVERA ES

INTERNATIONAL JOURNAL OF RADIATION BIOLOGY

TAYLOR & FRANCIS LTD

Año: 2011 vol. 87 p. 284 - 292

0955-3002

Purpose: 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. Materials and methods: Forty eight rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 hours before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a single dose of whole-body Cesium-137 irradiation. Control and untreated-5Gy 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 organization 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