Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 Compound, a histamine H4 ligand

Authors
Martinel Lamas, Diego José; Carabajal, Eliana; Prestifilippo, Juan Pablo; Rossi, Luis Francisco; Elverdin, Juan Carlos; Merani, Maria Susana; Bergoc, Rosa Maria; Rivera, Elena Susana; Medina, Vanina Araceli
Publication Year
2013
Language
English
Format
article
Status
Published version
Description
Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, 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. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG) function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01). This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01). JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy.
Fil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina;
Fil: Carabajal, Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina; Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina;
Fil: Prestifilippo, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina;
Fil: Rossi, Luis Francisco. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina;
Fil: Elverdin, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina; Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina;
Fil: Merani, Maria Susana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología. Centro de Investigación en Reproducción; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;
Fil: Bergoc, Rosa Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina;
Fil: Rivera, Elena Susana. Universidad de Buenos Aires; Argentina; Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina;
Fil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;
Subject
JNJ7777120
IONIZING RADIATION
RADIOPROTECTOR
SMALL INTESTINE
BONE MARROW
SALIVARY GLANDS
Oncología
Medicina Clínica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/1731