Effect of heme oxygenase-1 induction by octreotide on TNBS-induced colitis.

BACKGROUND AND AIM: Ulcerative colitis is a chronic inflammatory disease of the colon and rectum. Although the precise etiology of ulcerative colitis remains unknown, it is believed to involve an abnormal host response to endogenous or environmental antigens, genetic factors, and oxidative damage. The aim of the present study was to investigate whether heme oxygenase-1 (HO-1) induction by octreotide could protect against oxidative and inflammatory damage from induced colitis. METHODS: Rats received octreotide 50 microg/kg per day intraperitoneally for 5 days before 2,4,6 trinitrobenzene sulfonic acid (TNBS) solution administration and for 15 days following TNBS solution administration. Rats were killed on day 21, and colonic malondialdehyde (MDA) levels, glutathione (GSH) levels and HO-1 expression were measured. Nuclear factor (NF)-kappaB and HO-1 expression was evaluated by immunohistochemical examination of the colonic tissue. RESULTS: Rats with TNBS-induced colitis had significantly increased colonic MDA levels and HO-1 expression in comparison to the control group. Octreotide treatment was associated with increased HO-1 expression and GSH levels, but decreased MDA levels. Histopathological examination revealed that the intestinal mucosal structure was preserved in the octreotide-treated group. In addition, treatment with octreotide significantly increased HO-1 expression and decreased NF-kappaB expression by immunohistochemistry when compared to the TNBS-induced colitis group. CONCLUSION: Octreotide appears to have protective effects against colonic damage in TNBS-induced colitis. This protective effect is, in part, mediated by modification of the inflammatory response and the induction of HO-1 expression.

The effect of heme oxygenase-1 induction by glutamine on TNBS-induced colitis. The effect of glutamine on TNBS colitis.

BACKGROUND: Inflammatory bowel disease is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. In the present study, we aimed to investigate whether heme oxygenase-1 (HO-1) induction by glutamine could protect colitis-induced damage from oxidative, inflammatory, and apoptotic damage. METHOD: The rats were divided into four groups. Group 1 had TNBS colitis alone, group 2 had TNBS-induced colitis and glutamine 1 g/kg/day intragastric gavage for 3 days before TNBS solution administration and 15 days following TNBS solution administration, group 3 had glutamine alone 1 g/kg/day intragastric gavage for 18 days before being killed, and group 4 had isotonic saline solution alone 1 cm3/rat intragastric gavage for 18 days before being killed. Colonic malondialdehyde (MDA) levels, glutathione (GSH) levels, caspase-3 activities, and HO-1 expressions of the killed rats were measured. Nuclear factor kappa B (NF-kappaB) and HO-1 expression were evaluated by immunohistochemical examination of the colonic tissue. RESULT: TNBS-induced colitis significantly increased the colonic MDA levels, caspase-3 activities, and HO-1 expression in comparison to the control group. Glutamine treatment was associated with increased HO-1 expression and GSH levels and decreased MDA levels and caspase-3 activity. Histopathological examination revealed that the intestinal mucosal structure was preserved in the glutamine-treated group. In addition to this, treatment with glutamine significantly increased HO-1 expression and decreased NF-kappaB expression by immunohistochemistry when compared to the TNBS-induced colitis group. CONCLUSION: Glutamine reduced colonic damage in TNBS-induced colitis. The mechanism of the protection associated with glutamine was due to antioxidant, antiapoptotic, anti-inflammatory, and HO-1 induction effects.

The effect of octreotide on pancreatic damage in TNBS-induced colitis.

Inflammatory bowel disease, a chronic condition of the intestine, is associated with numerous extraintestinal manifestations, including pancreatitis. This study investigated the effect of octreotide administration on oxidative damage in a rat model of colitis induced by 2,4,6-trini-trobenzene sulfonic (TNBS) acid. Colonic and pancreatic malondialdehyde and glutathione levels are indicators of oxidative damage, and TNBS-induced colitis significantly increased the colonic and pancreatic malondialdehyde levels and decreased glutathione levels. Octreotide treatment was associated with decreased malondialdehyde levels and increased glutathione levels in the colonic and pancreatic tissue. The colonic mucosal structure was preserved and pancreatic inflammation decreased in rats treated with octreotide. Octreotide also significantly decreased nuclear factor-kB expression by immunohisto-chemistry in the colonic and pancreatic tissue compared with TNBS-induced colitis group. Octreotide appears to have protective effects against TNBS-induced colonic and pancreatic damage. These results imply the reduction in mucosal damage owing to the anti-inflammatory and antioxidant effects of octreotide.

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.