Abstract
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.
Highlights
Effective radiotherapy to treat cancer patients should include maximal tumor cell killing with minimal injury to normal tissue
Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed to investigate the radioprotective potential of the H4 receptor (H4R) ligand, JNJ7777120, evaluating its effect on reducing ionizing radiation-induced injury and genotoxic damage in the rat small intestine, salivary glands and hematopoietic tissue
This study aims to investigate the radioprotective effect of JNJ7777120 compound on gamma radiation-induced damage on small intestine, Submandibular gland (SMG) and hematopoietic tissue
Summary
Effective radiotherapy to treat cancer patients should include maximal tumor cell killing with minimal injury to normal tissue. The prevention or treatment of early and late radiotherapy effects would improve quality of life and increase cancer curability by intensifying therapies. In this sense, the role of radioprotective compounds is of utmost importance in clinical radiotherapy [1,2]. Side effects of pelvic or abdominal radiation therapy include nausea, diarrhea, and villous atrophy while radiation-induced xerostomia still represents a common adverse effect after radiotherapy for head-and-neck malignancies [1,2,3]
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