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

DIEGO MARTINEL LAMAS; ELIANA CARABAJAL; JUAN P PRESTIFILIPPO; LUIS ROSSI; JUAN C ELVERDIN; SUSANA MERANI; ROSA M BERGOC; ELENA S RIVERA; VANINA A MEDINA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 8 p. 1 - 13

1932-6203

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