RADIOPROTECTIVE EFFECT OF JNJ7777120 AGAINST CYTOTOXIC AND GENOTOXIC DAMAGE OF IONIZING RADIATION

DIEGO MARTINEL LAMAS; ELIANA CARABAJAL; JORGE CORTINA; PABLO CIRAOLO; ERIC RHON CALDERON; SUSANA MERANI; ELENA S RIVERA; VANINA A MEDINA

Congreso; European Histamine Research Society, XLII Annual Meeting; 2013

Radiotherapy is one of the most widely used local modality for the treatment of cancer. Despite its high therapeutic index, ionizing radiation can cause disabling normal tissue injury causing serious adverse effects to patients. We have previously reported the radioprotective effect of histamine on highly radiosensitive tissues. In the present work we aimed to investigate the possible mechanisms responsible for the radioprotective effect of the H4R ligand, JNJ7777120 (J77), evaluating its effect on reducing ionizing radiation-induced injury and genotoxic and oxidative damages in the rat small intestine and hematopoietic tissue. For that purpose, 40 rats were divided into 4 groups. J77 and J77-irradiated groups received a daily sc J77 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. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus (MN) assay and cytogenetic analysis were performed to evaluate chromosomal damage. Thiobarbituric acid reactive substances (TBARS) and catalase activity were determined by spectrophotometric techniques. Results indicate that J77 reduced the grade of aplasia, and substantially prevented ionizing radiation-induced bone marrow replacement by adipose tissue, preserving all medullar components. J77 decreased the percentage of MN formation (3% vs. 13%, P