JNJ7777120 Compound: a Potential Candidate for Use as Radioprotector.

VANINA A MEDINA; DIEGO MARTINEL LAMAS; MAXIMO CROCI; JUAN P PRESTIFILIPPO; ELIANA CARABAJAL; JUAN C ELVERDIN; ROSA M BERGOC; ELENA S RIVERA

Durham

Congreso; European Histamine Research Society, XXXIX Annual Meeting.; 2010

European Histamine Research Society

Radiation side effects are inevitable, even with localized radiotherapy. Based on our previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed to determine whether JNJ7777120 compound is able to protect bone marrow, small intestine and salivary glands against ionizing radiation damage. For that purpose, 48 rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 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. We evaluated the number of medullar components, bone marrow trophism, oedema, vascular damage, number of intestinal crypts per circumference, and other histological characteristics. We also determined proliferation and apoptosis markers by immunohistochemistry and metacholine-induced salivary secretion of submandibular gland (SMG). Results indicate that JNJ7777120 treatment reduced the grade of aplasia, and substantially prevented bone marrow replacement by adipose tissue produced by ionizing radiation, preserving medullar components. Furthermore, JNJ7777120 diminished mucosal atrophy, oedema and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10 in untreated and irradiated rats). Additionally, JNJ7777120 completely reversed the reduced salivation induced by radiation, significantly conserved glandular mass with normal appearance, preserved structure organization of secretor granules and reduced apoptosis in SMG. We conclude that JNJ7777120 compound prevents radiation-induced damage on bone marrow, small intestine and SMG being of potential clinical value for patients undergoing radiotherapy. We thank Dr. Nicholas Carruthers from Johnson & Johnson Pharmaceutical Research & Development for the JNJ7777120 compound.