Radioprotective potential of histamine on rat small intestine and uterus.
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 radioprotective 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.
Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
E
E
Carabajal
N
N
Massari
M
M
Croci
D J
DJ
Martinel Lamas
J P
JP
Prestifilippo
R M
RM
Bergoc
E S
ES
Rivera
V A
VA
Medina
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents; D006632:Histamine