Histamine And Its Ligands As Promising Radioprotectors Of Normal Tissues To Improve Radiotherapy

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

Congreso; XIII International Radioprotection Congress of the International Radiation Protection Association; 2012

Radiation side effects are inevitable, even with localized radiotherapy. Therefore, specific protection of normal tissues represents a promising approach to improve radiation therapy. The aim of the present work was to determine whether histamine and JNJ7777120 compound (H4 histamine receptor antagonist) are able to protect bone marrow, small intestine and salivary glands against ionizing radiation damage. For that purpose, male rats were divided into 8 groups (N=8 per group). Ligand treated and treated-irradiated groups received a daily subcutaneous injection (JNJ7777120 10 mg/kg; histamine 0.1 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. The number of medullar components, bone marrow trophism, oedema, vascular damage, number of intestinal crypts per circumference, and other histological characteristics were evaluated. Proliferation and apoptosis markers by immunohistochemistry and metacholine-induced salivary secretion of submandibular gland (SMG) were also determined. Results indicate that JNJ7777120 and histamine treatments reduced the grade of aplasia, and substantially prevented bone marrow replacement by adipose tissue produced by ionizing radiation, preserving all medullar components. Furthermore, JNJ7777120 and histamine diminished mucosal atrophy, oedema and preserved villi and the number of crypts after radiation exposure (240±8 in JNJ777120 treated and irradiated and 200±7 in histamine treated and irradiated groups vs. 165±10 in untreated and irradiated rats, P