Mechanisms underlying the radioprotective effect of histamine on small intestine.
OBJECTIVE
To examine the protective effects of histamine on intestinal damage produced by gamma-radiation.


METHODS
56 mice were divided into 4 groups. Histamine and Histamine-10 Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued until the end of the experimental period; the untreated group received saline. Histamine-10 Gy and untreated-10 Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Small intestine was removed, fixed and stained with hematoxylin and eosin. The number of intestinal crypts per circumference, and other histological characteristics of intestinal cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA), Bax, Bcl-2 (pro- and anti-apoptotic protein, respectively), antioxidant enzymes (Superoxide dismutase (SOD), Catalase and Glutathione peroxidase), histamine content and apoptosis by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) assay. Cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation.


RESULTS
Histamine treatment reduced mucosal atrophy, edema and preserved villi, crypts and nuclear and cytoplasmic characteristics of small intestine after radiation exposure. Additionally, histamine treatment increased PCNA expression and the BrdU-positive cell number, histamine content, decreased the number of apoptotic cells and significantly increased Catalase and copper-zinc-containing SOD of irradiated mice.


CONCLUSIONS
Histamine prevents radiation-induced toxicity by increasing proliferation of damaged intestinal mucosa and suppressing apoptosis that was associated with an increase in SOD and Catalase levels. This effect might be of clinical value in patients undergoing radiotherapy.
Medina
Vanina A
VA
Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires.
Croci
Máximo
M
Mohamad
Nora A
NA
Massari
Noelia
N
Garbarino
Gloria
G
Cricco
Graciela P
GP
Núñez
Mariel A
MA
Martín
Gabriela A
GA
Crescenti
Ernesto J V
EJ
Bergoc
Rosa M
RM
Rivera
Elena S
ES
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002587:Cesium Isotopes / Q000378:metabolism*; D003593:Cytoplasm / Q000473:pathology; D004487:Edema / Q000473:pathology; D006632:Histamine / Q000008:administration & dosage* / Q000494:pharmacology; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007410:Intestinal Diseases / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D010544:Peroxidases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000517:prevention & control* / Q000662:veterinary; D013997:Time Factors; D014916:Whole-Body Irradiation
D002587:Cesium Isotopes; D018809:Proliferating Cell Nuclear Antigen; D006632:Histamine; D010544:Peroxidases