The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis.
BACKGROUND
Radiation enteritis is a significant clinical problem in patients receiving ionizing radiation directed at the abdomen or pelvis. The small intestine is the most radiosensitive gastrointestinal organ. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels of the small intestine were measured to determine the oxidative damage caused by radiation. In addition, caspase-3 activity of the small intestine was measured to define the degree of apoptosis. The present study was undertaken to investigate the effect of glutamine administration on heme oxygenase-1 (HO-1) expression of the radiation enteritis model.


METHODS
Rats received 1 g/kg/d glutamine (HO-1-inducer) for 7 days before irradiation and continued for 3 days after irradiation. Zn-prothoporphyin (Zn-PP) 40 micromol/kg was delivered subcutaneously for 1 day before irradiation. Intestinal MPO activities and MDA levels are indicators of oxidative damage, whereas caspase-3 activities show the degree of apoptosis of the small intestine. At histopathologic examination, terminal ileum tissue was analyzed for morphologic changes. Also, the nuclear factor-kappa (NF-kappa) expression level of the terminal ileum was determined with immunohistochemistry methods to show the mucosal inflammatory process.


RESULTS
Irradiation significantly increased the intestinal MPO and caspase-3 activities, MDA levels, and HO-1 expression in comparison with the sham group. Glutamine treatment was associated with increased HO-1 expression, decreased MPO activity, caspase-3 activity, and MDA levels. Inhibition of HO-1 activity by Zn-PP completely eliminated the protective effects of glutamine. Histopathologic examination showed that the intestinal mucosal structure was preserved in the glutamine-treated group. In the irradiation group, NF-kappaB overexpression was detected. NF-kappaB positivity was strongest in the intestine of animals in the radiation alone group and the Zn-PP-treated irradiation group.


CONCLUSIONS
Glutamine appears to have protective effects against radiation-induced intestinal damage. This protective effect is mediated in part by the induction of HO-1 activity because inhibition of Zn-PP resulted in the complete abolishment of the protective effect of glutamine.
Department of Biochemistry, Istanbul University, Istanbul Medical Faculty, Capa, Istanbul, Turkey.
Murat
M
Giriş
Yeşim
Y
Erbil
Serdar
S
Oztezcan
Vakur
V
Olgaç
Umut
U
Barbaros
Uğur
U
Deveci
Banu
B
Kirgiz
Müjdat
M
Uysal
Gülçin Aykaç
GA
Toker
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004751:Enteritis / Q000188:drug therapy* / Q000209:etiology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000502:physiology*; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000528:radiation effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D005973:Glutamine; D008315:Malondialdehyde; D009195:Peroxidase; D051547:Heme Oxygenase-1; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases