The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis

• Published in: The American journal of surgery 2006-04, Vol.191 (4), p.503-509
• Main Authors: Giriş, Murat, Erbil, Yeşim, Öztezcan, Serdar, Olgaç, Vakur, Barbaros, Umut, Deveci, Uğur, Kirgiz, Banu, Uysal, Müjdat, Toker, Gülçin Aykaç
• Format: Article
• Language: English
• Subjects: Abdomen; Animals; Apoptosis; Biological and medical sciences; Blotting, Western; Caspase 3; Caspases - metabolism; Enteritis - drug therapy; Enteritis - etiology; Enzyme Induction - drug effects; Enzyme Inhibitors - pharmacology; Enzymes; Free radicals; Gastrointestinal diseases; General aspects; Glutamine; Glutamine - pharmacology; Heme oxygenase-1; Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - physiology; Intestinal Mucosa - enzymology; Intestinal Mucosa - radiation effects; Irradiation; Male; Malondialdehyde - metabolism; Medical sciences; Miscellaneous; NF-kappa B - metabolism; NF-κB; Peroxidase - metabolism; Potassium; Proteins; Radiation Injuries, Experimental - drug therapy; Radiation Injuries, Experimental - pathology; Radiation therapy; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Rats; Rats, Wistar; Rodents; Small intestine; Zn-prothoporphyin
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2005.11.004

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. 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 μmol/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-κ (NF-κ) expression level of the terminal ileum was determined with immunohistochemisty methods to show the mucosal inflammatory process. 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-κB overexpression was detected. NF-κB positivity was strongest in the intestine of animals in the radiation alone group and the Zn-PP–treated irradiation group. 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.