Radioprotective potential of histamine on rat small intestine and uterus

Abstract

The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239±12 vs 160±10; P<0.01). This effect was associated with a reduction of radiation-induced intestinal crypts apoptosis. Additionally, histamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats.The obtained evidences indicate that histamine is a potential candidate as a safe radio-protective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials.

Protection of Radiation-Induced Damage to the Hematopoietic System, Small Intestine and Salivary Glands in Rats by JNJ7777120 Compound, a Histamine H4 Ligand

“…In this regard, it was previously reported that histamine significantly protects in mice and rats two of the most radiosensitive tissues, small intestine and bone marrow, from high doses of gamma radiation [5–7]. In agreement with these data, histamine prevents functional and histological alterations of salivary glands produced by ionizing radiation [3].…”

“…Rats were maintained in our animal health care facility at 22 to 24°C and 50% to 60% humidity on a 12 h light/dark cycle with food and water available ad libitum . To determine the potential radioprotective effect of JNJ7777120 (Table 1) on small intestine, SMG and bone marrow we used the same experimental procedures that were previously described in detail [3,5–7]. Briefly, JNJ7777120 and JNJ7777120-5Gy groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg) starting 24 h before irradiation and which continued until 3 days post-irradiation while untreated groups received saline.…”

“…Tissue samples were embedded in paraffin and cut into serial sections of 4 µm thick. The histopathological characteristics were examined on tissue sections after hematoxylin-eosin (H&E) staining as it was previously described [3,6,7]. Also, specimens were stained with periodic acid schiff (PAS) staining and counterstained with hematoxylin to evaluate glycogen deposits.…”

“…Immunohistochemistry was performed as it was previously described [3,6,7]. Briefly, after blocking tissues were incubated with primary mouse anti-proliferating cell nuclear antigen (PCNA, 1:100, Dako Cytomation, Glostrup, Denmark), rabbit anti-aquaporin 5 (AQP5, 1:50, Abcam, Cambridge, MA, USA) or rabbit anti-H 4 R (1:100) (Alpha Diagnostic International, San Antonio, TX, USA), antibodies overnight in a humidified chamber at 4 ° C. Immunoreactivity was detected by using horseradish peroxidase-conjugated anti-mouse or anti-rabbit antibodies and visualized by diamino-benzidine staining (Sigma Chemical Co., St. Louis, MO, USA).…”

Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer

“…3,4 In this regard, it was reported that histamine significantly protects small intestine and bone marrow, from high doses of ionizing radiation, in 2 models of rodents. [5][6][7] In addition, histamine has the ability to prevent ionizing radiation-induced functional and histological alterations of salivary glands. 8 These features make histamine a suitable candidate as a radioprotector for patients undergoing radiotherapy.…”