Mechanisms underlying the Radioprotective Effect of Histamine on Small Intestine

VANINA A MEDINA; NORA A MOHAMAD; MÁXIMO CROCI; GRACIELA P CRICCO; MARIEL A NÚÑEZ; GABRIELA A MARTÍN; ROSA M BERGOC; ELENA S RIVERA

Delphi, Greece

Congreso; European Histamine Research Society. XXXV Annual Meeting; 2006

European Histamine Research Society

We have reported that histamine (HA) enhances radiosentivity of malignant cells and protects normal tissues from high doses of ionizing radiation (IR). HA reduces mucosal atrophy, edema and preserves villi, crypts and nuclear and cytoplasmic characters of small intestine after IR exposure. The aim of the present study was to investigate the mechanisms involved in Ha radioprotective effect.                                                   For this purpose, 36 mice were separated into 4 groups: Control (C), HA, irradiated (IR) and irradiated receiving HA (HA+IR). Irradiated animals received a single whole-body dose of 10 Gy. HA treated mice received a daily sc injection (0.1 mg/kg) during 5 days, starting 24 h before irradiation in the HA+IR group. All animals were sacrificed simultaneously after the experimental period. Antioxidant enzymes: superoxide dismutases (MnSOD and CuZnSOD), catalase (CAT) and glutathione peroxidase (Gpx) were determined by immunohistochemistry. In addition we evaluated HA content, expression of proliferating cell nuclear antigen (PCNA) and apoptosis by tunel assay.                                                   Results indicated that C group expressed PCNA in crypts, MnSOD only in villi, CAT, CuZnSOD, Gpx and HA in both villi and crypts. The only change exerted by HA was the appearance of MnSOD expression in crypts. On the other hand IR produced a marked decrease in Gpx, the complete disappearance of PCNA expression and an increase in apoptosis. In contrast, in HA+IR group, HA completely reverted the effect of IR on PCNA expression, decreased the number of apoptotic cells and significantly increased CAT and CuZnSOD in both villi and crypts. As well as in HA group, MnSOD was present in crypts.                                                   The data obtained clearly indicate that HA modulates the antioxidant enzymes, increases PCNA positive cells and inhibits apoptosis. Therefore HA may accelerate repair of damaged intestinal mucosae and/or increase proliferation and enhance antioxidant capacity, leading to the protection of small intestine against the cellular damage produced by IR.                                                     POSTER