Saadet Gumuslu

Alterations in brain antioxidant status, protein oxidation and lipid peroxidation in response to different stress models.

The aim of this study was to investigate the effects of different stress models on copper, zinc-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and selenium-dependent glutathione peroxidase (Se-GSH-Px) activities, and reduced glutathione (GSH), protein carbonyl (PC) and lipid peroxidation marker (conjugated diene (CD) and thiobarbituric acid-reactive substances (TBARS)) levels in brain of rats, and to determine the most effective stress model according to each parameter. Rats were divided into four groups as following: control group (C), immobilization stress group (IS), cold stress group (CS) and immobilization-cold stress group (ICS). All stress models increased brain Cu,Zn-SOD and CAT activities, PC, CD and TBARS levels, plasma corticosterone levels and decreased brain GSH concentrations. Se-GSH-Px activity was increased in CS and ICS groups. When all stress models were taken into consideration, the highest increases in Cu,Zn-SOD and Se-GSH-Px activities were found in CS group. The lowest GSH level was seen in IS group. The highest increases in PC and TBARS levels were found in ICS group. The highest increase of CD concentration was seen in IS and ICS groups. Our results suggest that different stress models have different degrees of influences on enzymatic and non-enzymatic antioxidant defense systems, protein oxidation and lipid peroxidation in the brain.

Interleukin-1β, Tumor Necrosis Factor-α, and Nitrite Levels in Febrile Seizures

Proinflammatory cytokines (such as interleukin-1β, tumor necrosis factor-α) and nitric oxide are known to have both direct and indirect modulating effects on neurons and neurotoxic neurotransmitters released during excitation or inflammation. We measured interleukin-1β, tumor necrosis factor-α, and nitrite levels in the peripheral blood and cerebrospinal fluid of children with febrile seizures and compared our results with those of children with febrile illnesses without seizures. Twenty-nine children with febrile seizure and 15 controls were studied. The mean concentrations of interleukin-1β and nitrite were significantly increased in the cerebrospinal fluid (P < .01) of the children with febrile seizure. There were no significant changes in serum interleukin-1β, tumor necrosis factor-α, nitrite, and cerebrospinal fluid tumor necrosis factorα levels. Our data support the hypothesis that increased production of interleukin-1β in the central nervous system or increased diffusion of interleukin-1β through the blood-brain barrier is involved in the pathogenesis of febrile seizures. (J Child Neurol 2002;17:749—751).

STRESS‐DEPENDENT INDUCTION OF PROTEIN OXIDATION, LIPID PEROXIDATION AND ANTI‐OXIDANTS IN PERIPHERAL TISSUES OF RATS: COMPARISON OF THREE STRESS MODELS (IMMOBILIZATION, COLD AND IMMOBILIZATION–COLD)

1 It is known that stress causes disruption of homeostasis and an imbalanced anti‐oxidant status in several organs. The aim of the present study was to determine the effects of three stress models on protein oxidation, lipid peroxidation and anti‐oxidant enzyme activities in the liver, kidney and heart, and to investigate the relationship between corticosterone and some oxidative stress parameters. In addition, we investigated the most effective stress model for each parameter in each tissue. 2 Thirty‐six male Wistar rats (aged 3 months old, weighing 220 ± 20 g) were divided randomly into four groups of nine rats each: control (C), immobilization stress (IS), cold stress (CS), and immobilization–cold stress (ICS). 3 Results showed that corticosterone levels were increased in all stress groups. Levels of protein carbonyl (PC), conjugated dienes (CD) and thiobarbituric acid‐reactive substances (TBARS) were increased, whereas reduced glutathione (GSH) levels were decreased in all tissues of all stress groups. Copper, zinc‐superoxide dismutase (Cu,Zn‐SOD) activities were increased in the liver and kidney of all stress groups, but were decreased in heart of the IS and CS groups. Catalase (CAT) activities were increased in liver of the CS group and in kidney and heart of all stress groups, but were decreased in liver of the IS and ICS groups. Selenium‐dependent glutathione peroxidase (Se‐GSH‐Px) activities were increased in liver of the CS and ICS groups and in heart of all stress groups, but were decreased in kidney of the IS group. Also, Se‐GSH‐Px activity levels remained unchanged in liver of the IS group and in kidney of the CS and ICS groups. The increased CAT activity and unchanged Se‐GSH‐Px activity observed in kidney suggest that H2O2 may be primarily scavenged by CAT. 4 The strong correlations between corticosterone and oxidative damage markers (e.g. protein oxidation, lipid peroxidation and GSH levels) suggest a relationship between these parameters. Liver was affected most by the CS model, whereas kidney and heart were affected most by ICS model. Stress‐induced changes in the activities of anti‐oxidant enzymes and GSH levels were found to be tissue‐ and enzyme‐specific. In conclusion, results of the present study suggest that each stress model affects the different organ tissues in different ways.

Cyclooxygenase-2 in cancer and angiogenesis.

Tumor angiogenesis is a process where new blood vessels are formed from preexisting ones, resulting in several pathologies. Solid tumors induce angiogenesis to obtain the required nutrients and oxygen. Otherwise, tumors do not grow beyond 2 to 3 mm in diameter. Cyclooxygenase-2, an inducible enzyme important in inflammation, catalyzes the production of prostanoids from arachidonic acid. Cyclooxygenase-2 plays an important role in several cancer types, including colorectal, gastric, prostate, breast, lung, and endometrial cancer. Besides, cyclooxygenase-2 has been implicated in the progression and angiogenesis of cancers. Cyclooxygenase-2 inhibitors have been used to block angiogenesis and tumor proliferation. In this review, the recent studies related to the role of cyclooxygenase-2 in several cancer types and tumor-induced angiogenesis were compiled.

THE EFFECT OF CHRONIC RESTRAINT STRESS ON SPATIAL LEARNING AND MEMORY: RELATION TO OXIDANT STRESS

The aim of this study was to investigate the effect of chronic restraint stress (RS) on spatial learning and memory. Fifty healthy male Wistar rats, aged three months were used. They were equally divided into five groups—C: Control, W: Water Maze, CS-1: Restrained for 21 days (1 h/day) + water maze protocol following stress period, CS-2: Restrained for 28 days (1 h/day) + water maze protocol during last 7 days of stress period, CS-3: Restrained for 21 days and allowed to recovery for 7 days (1 h/day). Corticosterone levels were higher in all stress groups than in C and W groups. Nitrite levels of frontal cortex and hippocampus were found to be elevated in chronic stress groups with respect to C and W groups. Thiobarbituric acid reactive substances (TBARS) of both tissues were increased significantly in CS1 and CS2 groups compared with C, W, and CS3 groups. Escape latencies of CS1 and CS2 groups were longer than those of the W group on each day of acquisition. In transfer test, CS1 and CS2 groups stayed significantly shorter in target quadrant according to the W group. Significant correlations between corticosterone and either nitrite or TBARS of hippocampus and frontal cortex were found. Both acquisition and memory performances were negatively correlated with plasma corticosterone level, nitrite, and TBARS levels of hippocampus and frontal cortex. The results of this study suggest that stress-induced lipid peroxidation may affect the acquisition and memory performances.

EFFECT OF SULFUR DIOXIDE ON ACTIVE AND PASSIVE AVOIDANCE IN EXPERIMENTAL DIABETES MELLITUS: RELATION TO OXIDANT STRESS AND ANTIOXIDANT ENZYMES

The effect of sulfur dioxide (SO2) on hippocampus antioxidant status, lipid peroxidation and learning and memory was investigated in diabetic rats. A total of 40 rats were divided into four equal groups: Control (C), SO2 + C (SO2), diabetic (DM) and SO2 + D (DMSO2). Experimental diabetes mellitus (DM) was induced by i.v injection of alloxan with a dose of 50 mg/kg body weight. Ten ppm SO2 was administered to the rats in the sulfur dioxide groups in an exposure chamber. Exposure occurred 1 h/d, 7 d/wk, for 6 wk; control rats were exposed to filtered air during the same time periods. SO2 exposure, while markedly increasing Cu-Zn Superoxide dismutase activity, significantly decreased glutathione peroxidase activity in diabetic and non-diabetic groups compared with the C group; hippocampus catalase activity was unaltered. Hippocampus thiobarbituric acid reactive substances (TBARS) were found to be elevated in all experimental groups with respect to control group. The active avoidance training results indicated that diabetic condition has been associated with learning and memory impairment. SO2 exposure caused deficits of learning and memory. Diabetes mellitus–induced impairment of learning and memory were potentiated by SO2 exposure. These findings suggest that exposure to SO2 by increasing lipid peroxidation, can change antioxidant enzyme activities and can elevated intensity of deficits of learning and memory in diabetic rats.

Antioxidant capacity of G-6-PD-deficient erythrocytes☆

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is the most common human enzymopathy. In this research, we studied two groups consisting of 30 male subjects who are G-6-PD deficient and 30 normal male subjects matched with the G-6-PD-deficient patients for age. All 30 assays were performed under normal conditions free of any oxidative attack that may result in haemolytic crisis in G-6-PD-deficient subjects. The erythrocyte glucose-6-phosphate dehydrogenase, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) activities, reduced glutathione (GSH) levels and erythrocyte and plasma thiobarbituric acid-reactive substances (TBARS) levels were measured. All parameters in each group did not differ significantly except for G-6-PD levels. These data show that G-6-PD-deficient subjects can survive in normal conditions unless they are exposed to any oxidative stress.

Influences of different stress models on the antioxidant status and lipid peroxidation in rat erythrocytes

The aim of this study was to investigate the influences of different stress models on the antioxidant status and lipid peroxidation (LPO) in erythrocytes of rats. Swiss-Albino female rats (3 months old) were used in this study. Rats were randomly divided into the following four groups; control group (C), cold stress group (CS), immobilization stress group (IS) and cold+immobilization stress group (CS+IS). Control group was kept in an animal laboratory (22 - 2°C). Rats in CS group were placed in cold room (5°C) for 15 min/day for 15 days. Rats in IS group were immobilized for 180 min/day for 15 days. Rats in CS+IS group were exposed to both cold and immobilization stresses for 15 days. At the end of experimental periods, the activities of glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and concentration of reduced glutathione (GSH) were measured. LPO was determined by measuring the contents of thiobarbituric acid-reactive substances (TBARS). Cu,Zn-SOD activity and TBARS concentration were increased after cold and immobilization stresses, but CAT and GSH-Px activities and GSH levels were decreased. Immobilization stress decreased the activity of G-6-PD. The activities of G-6-PD, CAT and GSH-Px, and the level of GSH were lower in CS+IS group than in the control group. Cu,Zn-SOD activity and TBARS levels were increased in CS+IS group when compared with the control group. From these findings, three stress models are thought to cause oxidative stress.

Changes in glucose-6-phosphate dehydrogenase, copper, zinc-superoxide dismutase and catalase activities, glutathione and its metabolizing enzymes, and lipid peroxidation in rat erythrocytes with age.

We have studied the activities of enzymes (glucose-6-phosphate dehydrogenase (G-6-PD), copper, zinc-superoxide dismutase (Cu,Zn-SOD), catalase (CAT), selenium-dependent glutathione peroxidase (Se-GSH-Px) and glutathione-S-transferase (GST)), and the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS) in rat erythrocytes and estimated the ratio of GSH/GSSG and the redox index. Male Wistar rats at ages of 1, 6 and 12 months were used. The activities of G-6-PD and Cu,Zn-SOD, the levels of GSSG and TBARS were increased, while the activity of Se-GSH-Px and the level of GSH were decreased with age. GSH/GSSG ratio was significantly decreased with age. We found a positive correlation between age and G-6-PD (r=0.476, p<0.01), Cu,Zn-SOD (r=0.291, p<0.01), CAT (r=0.254, p<0.01) and GST activities (r=0.250, p<0.05), and GSSG (r=0.708, p<0.05) and TBARS levels (r=0.802, p<0.01), whereas the correlation between age and Se-GSH-Px activity (r=-0.376, p<0.05), GSH level (r=-0.603, p<0.01) and GSH/GSSG ratio (r=-0.685, p<0.05) were negative. We found age-related differences in erythrocyte antioxidant enzyme activities, GSH, GSSG, total GSH and TBARS levels, GSH/GSSG ratio and the redox index.

Advanced oxidative protein products are independently associated with endothelial function in peritoneal dialysis patients

Aim:  Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as non‐classical cardiovascular risk factors in end‐stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS and ADMA are associated with endothelial function (EF) in peritoneal dialysis (PD) patients.