Serdar Öztezcan

The effect of selenium and/or vitamin E treatments on radiation-induced intestinal injury in rats.

Cytotoxic effects of ionizing radiation on gastrointestinal epithelium may be related to oxidative stress. In this study, we wanted to investigate the effects of selenium, vitamin E and selenium plus vitamin E pretreatments prior to whole abdominal irradiation on intestinal injury. Irradiation caused increased lipid peroxide and decreased GSH levels in the intestine. Intestinal superoxide dismutase and glutathione peroxidase activities were increased, but glutathione transferase activity decreased following irradiation. Selenium and/or vitamin E pretreatments ameliorated these disturbances in prooxidant-antioxidant balance. This amelioriation has been verified with histopathological findings. These results indicate that antioxidant pretreatments prior to irradiation may have some beneficial effects against irradiation-induced intestinal injury.

Age-related increases in plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in elderly subjects

OBJECTIVES Increased oxidative stress has been hypothesized to play an important role in the aging process. A role for oxidative damage in normal aging is supported by studies in experimental animals, but there is limited evidence in humans. To investigate the relationship between the oxidative stress and aging in humans, we determined lipid and protein oxidation in plasma as well as DNA damage in lymphocytes in young and elderly subjects. DESIGN AND METHODS 55 healthy subjects were divided into young (21-40 years) and elderly (61-85 years) groups. Plasma malondialdehyde (MDA), protein carbonyl (PC) levels, and grade of DNA damage in lymphocytes using comet assay as well as total ferric reducing antioxidant power (FRAP) in plasma were determined in young and elderly subjects. RESULTS Plasma MDA and PC levels were found to be increased in plasma of elderly subjects as compared to young subjects. Increases in endogenous and H2O2-induced DNA damage were also observed in lymphocytes of elderly subjects. In addition, we detected a significant decrease in FRAP values in elderly subjects. Plasma MDA, PC levels and endogenous and H2O2-induced DNA damage were positively correlated with aging, but negatively with FRAP values. CONCLUSION We evaluated MDA, PC levels and lymphocyte DNA damage altogether in both young and elderly subjects for the first time. The results of this study strongly support the presence of increased oxidative stress in elderly subjects.

Peroxisome Proliferator-Activated Receptor-γ-Mediated Positive Energy Balance in the Rat Is Associated with Reduced Sympathetic Drive to Adipose Tissues and Thyroid Status

Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation up-regulates thermogenesis-related genes in rodent white and brown adipose tissues (WAT and BAT) without increasing whole-body energy expenditure. We tested here whether such dissociation is the result of a negative modulation of sympathetic activity to WAT and BAT and thyroid axis components by PPARgamma activation. Administration of the PPARgamma agonist rosiglitazone (15 mg/kg.d) for 7 d to male Sprague Dawley rats increased food intake (10%), feed efficiency (31%), weight gain (45%), spontaneous motor activity (60%), and BAT and WAT mass and reduced whole-body oxygen consumption. Consistent with an anabolic setting, rosiglitazone markedly reduced sympathetic activity to BAT and WAT (>50%) and thyroid status as evidenced by reduced levels of plasma thyroid hormones (T(4) and T(3)) and mRNA levels of BAT and liver T(3)-generating enzymes iodothyronine type 2 (-40%) and type 1 (-32%) deiodinases, respectively. Rosiglitazone also decreased mRNA levels of the thyroid hormone receptor (THR) isoforms alpha1 (-34%) and beta (-66%) in BAT and isoforms alpha1 (-20%) and alpha2 (-47%) in retroperitoneal WAT. These metabolic effects were associated with a reduction in mRNA levels of the pro-energy expenditure peptides CRH and CART in specific hypothalamic nuclei. A direct central action of rosiglitazone is, however, unlikely based on its low brain uptake and lack of metabolic effects of intracerebroventricular administration. In conclusion, a reduction in BAT sympathetic activity and thyroid status appears to, at least partly, explain the PPARgamma-induced reduction in energy expenditure and the fact that up-regulation of thermogenic gene expression does not translate into functional stimulation of whole-body thermogenesis in vivo.

The effect of betaine treatment on triglyceride levels and oxidative stress in the liver of ethanol-treated guinea pigs.

We investigated the effect of betaine supplementation on ethanol induced steatosis and alterations in prooxidant and antioxidant status in the liver of guinea pigs. Animals were fed with normal chow or betaine containing chow (2% w/w) for 30 days. Ethanol (3 g/kg, i.p.) was given for the last 10 days. We found that ethanol treatment caused significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. Significant decreases in glutathione (GSH), alpha-tocopherol and total ascorbic acid (AA) levels were also observed, but hepatic superoxide dismutase, glutathione peroxidase and glutathione transferase activities remained unchanged as compared with those in controls. Betaine treatment together with ethanol in guinea pigs is found to decrease hepatic triglyceride, lipid peroxide levels and serum transaminase activities and to increase GSH levels. No changes in alpha-tocopherol and total AA levels and antioxidant enzyme activities were observed with betaine treatment in alcohol treated guinea pigs. In addition, histopathological assessment of guinea pigs showed that betaine reduced the alcoholic fat accumulation in the liver. Based on these data, betaine treatment has a restoring effect on the alterations in triglyceride, lipid peroxide and GSH levels following ethanol ingestion.

An increase in lipoprotein oxidation and endogenous lipid peroxides in serum of obese women.

Abstract. Endogenous malondialdehyde and diene conjugate levels, the susceptibility of apolipoprotein B-containing lipoproteins to copper-induced lipid peroxidation, and antibody titer against oxidized low-density lipoproteins were increased, but serum antioxidant activity was unchanged in obese women. Serum cholesterol, low-density lipoproteincholesterol, and trigliceride levels were also elevated, but high-density lipoprotein-cholesterol levels remained unchanged in obese women. In vitro, oxidation of apolipoprotein B-containing lipoproteins and levels of antibody against oxidized low-density lipoprotein correlated with body mass index, serum total cholesterol, and low-density lipoproteincholesterol levels in obese women. These results indicate that obesity is associated with increases in endogenous lipid peroxides, oxidation of low-density lipoproteins, and lipids in serum.

Effects of added dietary taurine on erythrocyte lipids and oxidative stress in rabbits fed a high cholesterol diet.

Lipid peroxidation leads to damage of polyunsaturated fatty acids of membrane phospholipids. The contribution of oxidative stress to hypercholesterolemia-induced hemolytic anemia and the effects of addition of taurine on erythrocyte lipid composition, oxidative stres, and hematological data were studied in rabbits fed on a high cholesterol (HC) diet (1%, w/w) for 2 months. The effects of taurine on erythrocyte hemolysis and H2O2-induced lipid peroxidation were investigated in normal rabbit erythrocytes in vitro. The HC diet resulted in increases in plasma lipids and lipid peroxide levels as well as increases in cholesterol levels and the cholesterol:phospholipid ratio in the erythrocytes. This diet caused a hemolytic anemia, but lipid peroxide levels remained unchanged in the erythrocytes of the rabbits. Taurine (2.5%, w/w) added to the food has an ameliorating effect on plasma lipids and lipid peroxide levels in rabbits fed on a HC diet. This treatment also caused decreases in elevated erythrocyte cholesterol levels and cholesterol:phospholipid ratio due to the HC diet, but it did not prevent the hemolytic anemia and did not change erythrocyte lipid peroxide levels. In addition, in an in vitro study, taurine did not protect erythrocytes against H2O2-induced hemolysis or lipid peroxidation. These results show that the HC diet causes hemolytic anemia without any changes in erythrocyte lipid peroxidation, and taurine treatment was not effective against hemolytic anemia caused by the HC diet.

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 μg/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, NFκ-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.

Effects of Carnosine Plus Vitamin E and Betaine Treatments on Oxidative Stress in Some Tissues of Aged Rats

Oxidative stress plays an important role in aging. Effects of several antioxidants on age-related oxidative stress have been investigated. Carnosine (CAR) and betaine have antioxidant actions. The combination of CAR with vitamin E(CAR+E) increases its antioxidant efficiency. We investigated the effects of CAR+E and betaine treatments on oxidative and antioxidative status in liver, heart and brain tissues of aged rats. Experiments were carried out on young (5 months)and aged (22 months) male Wistar rats. Aged rats were given CAR (250 mg/kg; i.p.; 5 days per week) and vitamin E (200mg/kg; i.m.; twice per week) or betaine (1% w/v) for two months. Malondialdehyde (MDA) and diene conjugate (DC)levels and antioxidants were measured. MDA and DC levels were higher in tissues of aged rats than young rats. Glutathione(GSH) levels decreased in liver, but not heart and brain. There were no changes in vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in tissues of aged rats. CAR+E treatment was observed to decrease MDA and DC levels in tissues of aged rats. However, betaine decreased only hepatic MDA and DC levels. Both CAR+E and betaine increased hepatic GSH and vitamin E levels, but these treatments did not affect antioxidant enzyme activities. These results suggest that CAR+E treatment seems to be useful to decrease oxidative stress in liver, heart and brain tissues, but betaine is only effective in liver tissue of aged rats.

The role of stimulated lipid peroxidation and impaired calcium sequestration in the enhancement of cocaine induced hepatotoxicity by ethanol

The purpose of this study was to investigate possible mechanism of cocaine-induced hepatotoxicity and its potentiation by ethanol in mice. Ethanol (2 g/kg) and/or cocaine (25 mg/kg) injections were given as binge model (five injections in 3 days). Cocaine administration with or without ethanol caused an increase in lipid peroxidation in liver homogenate and its subcellular fractions. The greatest increases were observed in mitochondrial fraction following cocaine plus ethanol treatment. Also, glutathione (GSH) levels were increased in liver homogenate and its mitochondrial fractions after cocaine and cocaine plus ethanol treatment. Microsomal calcium sequestration was found to decrease in all treatments. These results suggest that increased lipid peroxidation and decreased microsomal calcium sequestration in the liver may play a possible role cocaine-induced hepatotoxicity and its potentiation by ethanol.

Effect of a Taurine Treatment on the Regression of Existing Atherosclerotic Lesions in Rabbits Fed on a High-cholesterol Diet

We studied whether taurine has any regressive effect on existing atherosclerotic lesions and lipid peroxidation in rabbits fed on a high-cholesterol (HC) diet. The cholesterol, triglyceride, malondialdehyde (MDA) and diene conjugate (DC) levels, as well as the aortic histopathological findings were examined in rabbits that had been fed on a cholesterol-containing diet for 8 months [0.5% cholesterol (w/w) for 3 months and subsequently 0.25% cholesterol (w/w) for 5 months], and then for a further 4 months on a normal diet with or without taurine treatment [1% (w/v) in the drinking water]. High levels of lipid and lipid peroxide induced by the HC diet were observed to decline in the plasma, liver and aorta of atherosclerotic rabbits, as well as a slight retardation in aortic atherosclerotic lesions during the regression period. Although no significant differences in the lipid and lipid peroxide levels in the plasma and aorta were found between the regressed groups with or without the taurine treatment, the extent of atherosclerotic lesions in the aorta was less in the taurine-treated regressed group than in the non-treated regressed group. However, the liver MDA and DC levels were lower in the regressed rabbits with the taurine treatment in the non-treated group. These results indicate that the taurine treatment may accelerate the regression of cholesterol-induced atherosclerotic lesions in rabbits without having any effect on the plasma and aorta lipid and lipid peroxide levels.