Effect of betaine treatment on the regression of existing hepatic triglyceride accumulation and oxidative stress in rats fed on high fructose diet.

We investigated whether betaine has any regressive effect on existing high fructose diet (HFrD)-induced insulin resistance, dyslipidemia, inflammation as well as hepatic steatosis and oxidative stress. Rats were fed a HFrD containing 60% fructose for 8 weeks. After 8 weeks, rats were divided into two groups and fed a control diet for an additional 4-week period (regression groups). One of the regression groups received drinking water containing betaine (1%; w/v), having antioxidant and anti-inflammatory actions. HFrD feeding caused insulin resistance, elevated triglyceride (TG) and tumor necrosis factor-alfa (TNF-α) levels, alanine aminotransferase (ALT) and aspartate transaminase (AST) activities in serum. This diet increased hepatic TG, thiobarbituric acid reactive substances (TBARS) and diene conjugate (DC) levels, decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Marked macro-vesicular steatosis were detected. Serum TNF-α and ALT, hepatic TG, TBARS and DC levels and steatosis scores decreased in regression period of HFrD-fed rats. Additionally, serum TNF-α, hepatic TG, TBARS and DC levels significantly lower in betaine-treated regressed rats than non-treated regressed group. Our results indicate that betaine treatment may accelerate regression of HFrD-induced hepatic TG accumulation and oxidative stress in rats.

Elevated IL-4 and IFN-γ Levels in Muscle Tissue of Patients with Dermatomyositis.

BACKGROUND/AIM: To investigate the contribution of muscle tissue-derived cytokines in dermatomyositis (DM). MATERIALS AND METHODS: Muscle homogenates were prepared from deltoid muscle biopsy specimens of 10 patients with DM and eight controls with no pathological signs of myopathy. Interleukin (IL)-4, interferon (IFN)-γ and IL-17 levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis. Muscle strength grades were recorded. RESULTS: Patients with DM showed significantly elevated muscle tissue IL-4 and IFN-γ levels, whereas IL-17 levels were comparable between patients with DM and controls. Immunoblotting studies confirmed ELISA results. In DM muscle specimens, IL-4 and IFN-γ levels were positively correlated, while no correlation was observed between IL-17 and the other two cytokines. Moreover, IL-4 and IFN-γ levels were significantly negative correlated with muscle strength grades for the deltoid muscle. CONCLUSION: Our results confirm the involvement of T helper (Th) 1-type and Th2-type immunity in DM pathogenesis. Muscle tissue appears to contribute to muscle weakness in DM by producing inflammatory cytokines.

Impact of Neuro-Behçet Disease Immunoglobulin G on Neuronal Apoptosis.

INTRODUCTION: Parenchymal neuro-Behçet disease (NBD) is encountered in 5%-15% of Behçet disease (BD) patients and is characterized by inflammation of the brainstem and diencephalon structures. Neuronal apoptosis has been shown to participate in neuronal cell loss. Anti-neuronal antibodies have been identified in NBD patients. However, the pathogenic properties of these antibodies have not been studied. METHODS: To delineate the potential pathogenic activity of serum antibodies on neurons, pooled sera from seven NBD patients and seven healthy controls were divided into purified immunoglobulin G (IgG) and IgG-depleted serum fractions, and each fraction was administered to cultured SH-SY5Y neuroblastoma cells. Cell death was evaluated with a toxicity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Moreover, expression levels of several apoptosis markers were evaluated with real time polymerase chain reaction (PCR). RESULTS: Administration of NBD IgG to cultured SH-SY5Y cells induced significantly increased cell death and apoptosis compared with other treatments. NBD IgG also enhanced the mRNA expression levels of major apoptosis and cell survival pathway factors. CONCLUSION: Our results suggest that IgGs isolated from the sera of NBD patients have a neurotoxic activity that is presumably mediated by apoptotic mechanisms.

Viability of SH-SY5Y cells is associated with purinergic P2 receptor expression alterations.

To investigate the role of metabotrophic purinergic P2Y receptors in neuroblastoma cell survival, expression of P2 receptors by normal mouse (C57BL/6) brain and human neuroblastoma SH-SY5Y cells was investigated by Western blot and real time PCR studies. Viability of SH-SY5Y cells treated with purinergic receptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) was evaluated by MTT assay and flow cytometry. In the brain samples of C57BL/6 mice, expressions of P2Y4 and P2X7 were significantly reduced, whereas that of P2Y1 was significantly elevated in an age-dependent manner. SH-SY5Y cell viability was significantly reduced and necrotic cell rates were mildly increased by 400 µM suramin and 100 µM PPADS treatment. Antagonist treatment downregulated P2Y1, P2Y2 and P2Y4 and upregulated P2Y6, P2Y12 and P2X7 mRNA levels in SH-SY5Y cells on the 24th hour. These alterations were abolished for all P2 receptors except P2Y1 in the 48th hour. P2Y receptors are expressed by both normal mouse brain and human neuroblastoma cells. Purinergic receptor antagonism interferes with neuroblastoma viability through elevation of necrotic cell death and modulation of P2 receptor expression. P2Y receptors might thus be useful targets for future anti-tumor treatment trials.

Dynamic collagen changes in cervix during the first trimester and decreased collagen content in cervical insufficiency.

OBJECTIVE: To determine the changes in cervical collagen during the first trimester of pregnancy and to evaluate the collagen deficit in cases with a previous diagnosis of cervical insufficiency (CI). MATERIALS AND METHODS: Cervical punch biopsies were obtained from 66 patients divided into three groups: patients with recurrent abortions due to CI (CI group; n = 8); first-trimester abortion group (study group; n = 37), subdivided into three groups according their gestational week (<7, 7-9 and 9-12 weeks), and patients with cervical biopsy due to gynecologic reasons (control group; n = 12). Collagen quantity was determined by a biochemical method that measured the levels of hydroxyproline (HOP) in dry cervix tissue. RESULTS: The HOP concentrations were significantly higher at lower gestational ages (p = 0.001). Collagen quantity was lowest in the CI group compared with other groups (p < 0.001). CONCLUSION: This study shows collagen component of cervix decreases as pregnancy advances through the first trimester. Cervical collagen concentration is lower in women with a history of CI compared to controls who has not a history of CI.

A case of hyperkinetic movement disorder associated with LGI1 antibodies.

Encephalitis associated with leucine-rich glioma inactivated 1 (LGI1) antibodies is often encountered in elderly male patients and may infrequently present with isolated syndromes. A 6-year-old boy was admitted with acute onset severe oral and facial stereotypic and choreiform movements. On his neurologic examination, he had repetitive and rhythmic movements in orolingual muscles including tongue protrusion, limb chorea and minimal facial stereotypic movements. Anti-streptolysin O (ASO) titers were found severely elevated in several measurements. Well-characterized antibodies against ion channels and synapse proteins were negative whereas LGI1 antibody was positive in both serum and CSF. Marked clinical improvement was observed after immunotherapy. Here, we present the first pediatric case with LGI1 antibody associated hyperkinetic movement disorders and emphasize the importance of investigating neuronal autoantibodies in patients with isolated and treatment resistant movement disorders.

Response of liver to lipopolysaccharide treatment in male and female rats.

Gender is considered to be an important factor in endotoxin-induced tissue damage. Our aim was to examine the role of sex on the prooxidant-antioxidant status, necrotic and apoptotic events in the liver of lipopolysaccharide (LPS)-treated rats. We determined levels of lipid peroxides, non-enzymatic and enzymatic antioxidants, and expressions of apoptosis-related proteins, antiapoptotic B cell lymphoma-2 (Bcl-2) and proapoptotic Bax, caspase-3 activity and apoptotic cell numbers in the liver. Hepatic histopathology and serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were also investigated. Male and female Wistar rats (180-200 g) were injected with LPS (10 mg/kg, i.p.) and examinations were performed 6 h after the injection. Significant increases in hepatic thiobarbituric acid reactive substances and diene conjugate levels were observed in male and female rats following LPS treatment. However, there were no changes in hepatic glutathione, vitamin E and vitamin C levels together with superoxide dismutase, glutathione peroxidase and glutathione transferase activities. LPS treatment caused significant increases in serum ALT and AST activities and lymphocyte infiltration and necrotic changes in the livers. Bcl-2 and Bax expressions, caspase-3 activity and apoptotic cell numbers were also found to be increased in both groups. In conclusion, no sex-dependent difference was observed in the changed hepatic prooxidant-antioxidant status of rats following LPS treatment. Besides, the process leading to apoptosis and necrosis in the liver showed a similar pattern in both gender of rats.

Oxidative and nitrosative stress and apoptosis in the liver of rats fed on high methionine diet: protective effect of taurine.

OBJECTIVE: There are few reports about the direct toxic effects of hyperhomocysteinemia on the liver. We investigated oxidative and nitrosative stresses and apoptotic and necrotic changes in the liver of rats fed a high-methionine (HM) diet (2%, w/w) for 6 mo. We also investigated whether taurine, an antioxidant amino acid, is protective against an HM-diet-induced toxicity in the liver. METHODS: Lipid peroxide levels, nitrotyrosine formation, and non-enzymatic and enzymatic antioxidants were determined in livers of rats fed an HM diet. In addition, apoptosis-related proteins, proapoptotic Bax and antiapoptotic B-cell lymphoma-2 expressions, apoptotic cell count, histopathologic appearance in the liver, and alanine transaminase and aspartate transaminase activities in the serum were investigated. RESULTS: Plasma homocysteine levels and serum alanine transaminase and aspartate transaminase activities were increased after the HM diet. This diet resulted in increases in lipid peroxide and nitrotyrosine levels and decreases in non-enzymatic and enzymatic antioxidants in liver homogenates in rats. Bax expression increased, B-cell lymphoma-2 expression decreased, and apoptotic cell number increased in livers of rats fed an HM diet. Inflammatory reactions, microvesicular steatosis, and hepatocyte degeneration were observed in the liver after the HM diet. Taurine (1.5%, w/v, in drinking water) administration and the HM diet for 6 mo was found to decrease serum alanine transaminase and aspartate transaminase activities, hepatic lipid peroxide levels, and nitrotyrosine formation without any change in serum homocysteine levels. Decreases in Bax expression, increases in B-cell lymphoma-2 expression, decreases in apoptotic cell number, and amelioration of histopathologic findings were observed in livers of rats fed with the taurine plus HM diet. CONCLUSION: Our results indicate that taurine has protective effects on hyperhomocysteinemia-induced toxicity by decreasing oxidative and nitrosative stresses, apoptosis, and necrosis in the liver.

The effect of anti-thyroid drug treatment duration on thyroid gland microvessel density and intraoperative blood loss in patients with Graves' disease.

BACKGROUND: Preoperative preparation of the patient with Graves' disease (GD) is crucial to avoid intraoperative or postoperative complications associated with anesthesia or surgery. We aimed to evaluate thyroid blood flow and microvessel density in patients with GD according to antithyroid drug (ATD) treatment, preoperatively. METHOD: Forty-three patients were divided into two groups according to the ATD type. Patients in group 1 (n = 25) were treated with methimazole, whereas patients in group 2 (n = 18) were treated with propylthiouracil, preoperatively. Blood flow through the thyroid arteries was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed immunohistochemically and via Western blot analysis using the level of CD-34expression in thyroid tissue. RESULTS: There was a positive correlation between blood loss and thyroid volume (r(s) = 0.953, P = .0001) and blood flow (r(s) = 0.720, P = .0001) and CD-34 expression (r(s) = 0.331, P = .03) and MVD (r(s) = 0.442, P = .003). No correlation was observed between ATD type and thyroid vascularity. In patients with longer treatment duration before operation, thyroid vascularity was significantly lower relative to patients with shorter treatment durations. According to logistic regression analysis, longer treatment duration had a 142-fold decreased rate of intraoperative blood loss independent of ATD type. CONCLUSION: Preoperative ATD treatment duration may predict intraoperative blood loss during thyroidectomy. Longer treatment duration might be useful in reducing intraoperative bleeding, allowing better visualization and preservation of the nerves and parathyroid glands.

Early prediction of anastomotic leakage after colorectal surgery by measuring peritoneal cytokines: prospective study.

BACKGROUND: Anastomotic leakage (AL) is a major cause of postoperative mortality and morbidity in colorectal surgery. We investigated the early prediction of peritoneal cytokine levels in developing AL after colorectal surgery. METHODS: Thirty-four patients with colorectal carcinoma, who underwent elective surgery, were included prospectively. Peritoneal samples were collected on the fifth postoperative day and interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha were measured. Patients were divided into two groups: those with clinical evidence of AL (group 1) and those without any evidence of AL (group 2). RESULTS: Of the 34 patients undergoing anastomoses, clinically evident AL occurred in 4 patients (11.7%). There was a positive correlation between AL and peritoneal cytokine levels and blood loss and operation time and hospital stay. Peritoneal cytokine levels were significantly higher in group 1 as compared to group 2. The significant increase in patients with AL was observed between peritoneal cytokine levels and the postoperative days. However, a significant decrease in patients without AL was observed. CONCLUSION: The peritoneal cytokine levels can be an additional diagnostic tool that can support the early prediction of AL in colorectal surgery.

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 glutamine on pancreatic damage in TNBS-induced colitis.

Ulcerative colitis is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. The present study was undertaken to investigate the effect of glutamine administration on oxidative damage and apoptosis in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Rats received 1 g/kg/day glutamine for intragastric gavage for 7 days before TNBS solution administration and 3 days following TNBS solution administration until sacrifice. Then colonic and pancreatic malondialdehyde (MDA) and glutathione (GSH) levels, and colonic caspase-3 activities of the sacrified rats were measured. TNBS-induced colitis caused significantly increased in the caspase-3 activity and colonic and pancreatic MDA levels and decreased colonic and pancreatic GSH levels compared to those in the sham group. Glutamine treatment was associated with decreased MDA levels and caspase-3 activity and increased GSH levels in the colinic and pancreatic tissue. Histopathological examination revealed that the colonic mucosal structure was preserved and pancreatic inflammation decreased in the glutamine-treated group. In conclusion, glutamine appears to have protective effects against TNBS-induced colonic and pancreatic damage. These results imply a reduction in mucosal damage due to anti-inflammatory and antiapoptotic effects of glutamine.

The effect of melatonin on TNBS-induced colitis.

Ulcerative colitis is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. The present study was undertaken to investigate the effect of melatonin administration on oxidative damage and apoptosis in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Rats were divided into four groups as follows: Group 1 (n=8)-T-NBS colitis; Group 2 (n=8)--melatonin, 10 mg/kg/day ip, for 15 days in addition to TNBS; Group 3 (n=8)--melatonin alone, 10 mg/kg/day ip, for 15 days; and Group 4 (n=8)-isotonic saline solution, 1 ml/rat ip, for 15 days (sham control group). Colonic myeloperoxidase (MPO) activities, malondialdehyde (MDA) levels, and glutathione (GSH) levels are indicators of oxidative damage, while caspase-3 activities reveal the degree of apoptosis of the colonic tissue. In all TNBS-treated rats, colonic MPO activity and MDA levels were found to be increased significantly compared to those in the sham group. Colonic MPO activity and MDA levels were significantly lower in the melatonin treatment group compared to TNBS-treated rats. GSH levels of colonic tissues were found to be significantly lower in TNBS-treated rats compared to the sham group. Treatment with melatonin significantly increased GSH levels compared to those in TNBS-treated rats. Caspas-3 activity of colonic tissues was found to be significantly higher in TNBS-treated rats compared to the sham group. Treatment with melatonin significantly decreased caspase-3 activity compared to that in TNBS-treated rats. These results imply a reduction in mucosal damage due to anti-inflammatory and anti-apoptotic effects of melatonin.

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.

The efficacy of octreotide in pancreatic and intestinal changes: radiation-induced enteritis in animals.

Radiation enteritis occurs during the radiotherapy of many intraabdominal malignancies. Radiation induces cellular injury directly and through the generation of free radicals. In the present study we aimed to investigate the effect of octreotide (OCT) pretreatment in irradiation-induced enteritis. For this aim, rats were injected with 50 microg/kg OCT 4 days before irradiation and continued for 3 more days, until sacrifice. Then intestinal and pancreatic myeloperoxidase (MPO) activities and intestinal malondialdehyde (MDA) levels of the rats were measured. Irradiation significantly increased intestinal and pancreatic MPO activities and MDA levels of intestinal tissues in comparison to those of the sham group. OCT treatment improved this elevation. The histopathologic evaluation of the mucosal structure was also preserved in the OCT-treated group. Inflammation of pancreatic tissue was also confirmed with histopathological examinations. In the irradiation group, NFkappa-B overexpression was detected. OCT treatment decreased the end organ damage and inflammation of the small intestine. In conclusion, OCT appears to have beneficial effects on intestinal and pancreatic damage in abdominal irradiation through the inflammatory process.

The effect of heme oxygenase-1 induction by octreotide on radiation enteritis.

Radiation enteritis occurs as a response to abdominal radiation, which can cause mucosal damage in the gastrointestinal mucosal epithelium. The small intestine is one of the most radiosensitive organs in the abdomen. The present study was undertaken to investigate the effect of octreotide (OCT) administration on heme oxygenase-1 (HO-1) expression of the radiation enteritis model. Rats received 50 mg/kg/day OCT for 4 days before irradiation and continued for 3 days after irradiation. Intestinal myeloperoxidase (MPO) activities, malondialdehyde (MDA) levels are indicators of oxidative damage while caspase-3 activities reveal apoptosis degree of the small intestine. At histological examination, the terminal ileum tissue was analyzed for morphological changes. Irradiation significantly increased the intestinal MPO and caspase-3 activities, MDA levels and HO-1 expression in comparison to sham control group. OCT treatment was associated with increased HO-1 expression and caspase-3 activity, decreased MPO activity and MDA levels. Histological examination revealed that the intestinal mucosal structure was preserved in the OCT treated group. OCT appears to have protective effects against radiation-induced intestinal damage. This protective effect is, in part, mediated by modification of the inflammatory response and the induction of HO-1 expression.

The effect of glutamine on radiation-induced organ damage.

Radiation enteritis is a significant clinical problem in patients receiving ionizing radiation directed to the abdomen or pelvis. Although radiation is aimed to be directed against the malignant tissue, adjacent healthy tissues are also affected. The small intestine is the most sensitive organ to radiation. The present study was undertaken to investigate the possible protective effect of glutamine against radiation-induced intestinal, hepatic and pancreatic toxicity. Rats received 1 g/kg/day glutamine for seven days before irradiation and continued for three days after irradiation until sacrifice. Then intestinal, pancreatic and hepatic myeloperoxidase (MPO) activities, malondialdehyde (MDA) levels and caspase-3 activities of the sacrificed rats were measured. Irradiation significantly increased the intestinal and pancreatic MPO and caspase-3 activities and MDA levels in comparison to sham group. Glutamine treatment significantly decreased this elevation. Histopathological examination revealed that the intestinal mucosal structure was preserved and pancreatic inflammation decreased in the glutamine treated group. In irradiation group, NF-kappaB over expression was detected. There was no significant difference in histopathological and biochemical examinations of the liver between the groups. In conclusion, glutamine has beneficial effects on intestinal and pancreatic damage in abdominal irradiation through the inflammatory process and apoptosis.

Peroxynitrite induced decrease in Na+, K+-ATPase activity is restored by taurine.

AIM: Peroxynitrite (ONOO-) is a powerful oxidant shown to damage membranes. In the present study, the effect of taurine on changes of liver plasma membrane Na+, K+-ATPase induced by ONOO- was investigated. METHODS: Liver plasma membrane was exposed to ONOO- with or without taurine. Na+, K+-ATPase activity and lipid peroxidation as thiobarbituric acid reactive substances (TBARS) levels were measured. RESULTS: Different concentrations of ONOO- (100, 200, 500, and 1000 micromol/L) were found to decrease liver plasma membrane Na+, K+-ATPase activity significantly. The depletion of enzyme activity was not concentration dependent. Effects of different concentrations of taurine on liver plasma membrane Na+, K+-ATPase activity were also measured. Taurine did not cause any increase in enzyme activity. When plasma membranes were treated with 200 micromol/L ONOO- with different concentrations of taurine, a restoring effect of taurine on enzyme activity was observed. TBARS levels were also measured and taurine was found to decrease the elevated values. CONCLUSION: Taurine is observed to act as an antioxidant of ONOO- to decrease lipid peroxidation and thus affect liver plasma membrane Na+, K+-ATPase by restoring its activity.