Vural Kucukatay

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.

Grape seed extract has superior beneficial effects than vitamin E on oxidative stress and apoptosis in the hippocampus of streptozotocin induced diabetic rats.

We aimed to investigate the effects of grape seed extract (GSE) and vitamin E (Vit E) on oxidative stress and apoptosis in the hippocampus of streptozotocin-induced diabetic rats. In Control, Diabetic, and Diabetic treated with GSE (Diabetic+GSE) and vitamin E (Diabetic+Vit E) groups, oxidative stress index (OSI), TUNEL staining and Bcl-2, Bcl-XL, Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were evaluated. OSI was significantly increased in the plasma and hippocampus of the Diabetic compared to Control group and decreased in Diabetic+GSE and Diabetic+Vit E groups compared to Diabetic. TUNEL positive neurons significantly increased in the hippocampus of the Diabetic group compared to Control and decreased in Diabetic+GSE (more prominently) and Diabetic+Vit E groups compared to Diabetic. In the hippocampus of the Diabetic group, Bcl-2 and Bcl-XL gene expressions were significantly decreased; Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were significantly increased compared to Control. In Diabetic+GSE and Diabetic+Vit E groups, Bcl-2 gene expressions were significantly increased; Bcl-XL gene expressions did not differ compared to the Diabetic group. The expression of Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB genes in the Diabetic+GSE group and the expression of caspase-3 and -9, TNF-α, and NF-κB genes in the Diabetic+Vit E group were significantly decreased compared to Diabetic. In conclusion, GSE (more prominently) and vitamin E decreased oxidative stress and neuronal apoptosis occurring in the hippocampus of diabetic rats.

Hemorheological responses to progressive resistance exercise training in healthy young males.

Summary Background This study aimed to explore the effects of progressive resistance exercise training (PRET) on hemorheology. Material/Methods Exercise sessions included 1–3 sets of 8–12 repetitions at 40–60% of 1-repetition maximum (1-RM) for 3 weeks and at 75–80% of 1-RM during weeks 4–12. Red blood cell (RBC) deformability and aggregation were determined by ektacytometry, plasma and whole blood viscosities (WBV) by rotational viscometry. Lactate concentration was evaluated by an analyzer and fibrinogen was evaluated by coagulometry. Plasma total oxidant/antioxidant status was measured by colorimetry. Results Following an acute increase after exercise on the first day, RBC deformability was elevated during weeks 3 and 4 (p=0.028; p=0.034, respectively). The last exercise protocol applied in week 12 again caused an acute increase in this parameter (p=0.034). RBC aggregation was increased acutely on the first day, but decreased after that throughout the protocol (p<0.05). At weeks 4 and 12 pre-exercise measurements of WBV at standard hematocrit and plasma viscosity were decreased (p=0.05; p=0.041, respectively), while post-exercise values were increased (p=0.005; p=0.04, respectively). Post-exercise WBV at autologous hematocrit measured at week 12 was increased (p=0.01). Lactate was elevated after each exercise session (p<0.05). Fibrinogen was decreased on the third week (p<0.01), while it was increased on the 4th week (p=0.005). Plasma antioxidant status was increased at week 3 (p=0.034) and oxidative stress index was decreased at week 4 (p=0.013) after exercise. Conclusions The results of this study indicate that PRET may have positive effects on hemorheological parameters.

Hippocampal neuron number loss in rats exposed to ingested sulfite

Sulfite, which is continuously formed in the body during metabolism of sulfur-containing amino acids, is commonly used in preservatives. It has been shown that there are toxic effects of sulfite on many cellular components. The aim of this study was to investigate the possible toxic effects of sulfite on pyramidal neurons by counting cell numbers in CA1 and CA2-CA3 subdivisions of the rat hippocampus. For this purpose, male albino rats were divided into a control group and a sulfite group (25 mg/kg). Sulfite was administered to the animals via drinking water for 8 weeks. At the end of the experimental period, brains were removed and neurons were estimated in total and in a known fraction of CA1 and CA2-CA3 subdivisions of the left hippocampus by using the optical fractionator method—a stereological method. Results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA2-CA3) in the sulfite group compared with the control group (p < 0.05, Mann Whitney U test). It was concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA2-CA3 subdivisions of the rat hippocampus.

HEMORHEOLOGICAL PARAMETERS IN CHILDREN WITH IRON-DEFICIENCY ANEMIA AND THE ALTERATIONS IN THESE PARAMETERS IN RESPONSE TO IRON REPLACEMENT

Aim: Iron-deficiency anemia (IDA) is a common disorder in pediatric patients. There are a limited number of studies having controversial results in investigating red blood cell (RBC) deformability and aggregation in adult IDA patients. The aim of this study is to determine the change of hemorheological parameters, including RBC deformability, aggregation, and plasma and whole blood viscosity, in children with IDA following iron supplementation therapy. Materials and Methods: The study was performed on 20 children with IDA (average age 35.5 ± 6.5 months) and 20 age-matched healthy children. The anemia group was treated with 5 mg/kg/day peroral iron for 2 months. Hematological and hemorheological parameters were determined before and after treatment. An ectacytometer was used for the assessment of RBC deformability and aggregation and a cone-plate rotational viscometer for plasma and whole blood viscosities. Hematological parameters were determined using an electronic hematology analyzer. Results: Although IDA resulted in a decrement in RBC deformability, aggregation, plasma, and whole blood viscosities, these parameters returned to control values after iron supplementation therapy. Serum ferritin levels and hematological parameters (Hb, MCV, MCH, MCHC) that were lower in IDA patients were also found to be increased after treatment. Conclusion: Iron treatment not only reverses the symptoms of anemia but also may contribute to blood flow regulation by causing increments in the alterations observed in hemorheological parameters during anemia.

EFFECT OF INGESTED SULFITE ON HIPPOCAMPUS ANTIOXIDANT ENZYME ACTIVITIES IN SULFITE OXIDASE COMPETENT AND DEFICIENT RATS

Animal tissues are exposed to sulfite used as a preservative in food and drugs, and generated from the catabolism of sulfur-containing amino acids. Sulfite, which is a very reactive and potentially toxic molecule, is detoxified by the enzyme sulfite oxidase (SOX). Laboratory animals can be made deficient in SOX by the administration of a high-tungsten/low molybdenum regimen. It has been suggested that SOX deficient rats might be used as a model for the prediction of sulfite toxicity in humans. The aim of this study was to investigate the effects of ingested sulfite on hippocampus superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in SOX competent and deficient rats. Hippocampus SOD, CAT and GPx activities were found to be significantly increased by sulfite treatment in SOX competent groups. On the other hand, exposure to sulfite had no effect on antioxidant status in hippocampus of SOX deficient rats. In conclusion, these results suggest that hippocampus antioxidant capacity where defense mechanism against the oxidative challenge is up regulated by sulfite in SOX competent rats. This up regulation mechanism in antioxidant enzymes against to sulfite related oxidative stress is not observed in SOX deficient rats and remains to be explained.

Sulfite leads to neuron loss in the hippocampus of both normal and SOX-deficient rats.

Sulfites are compounds commonly used as preservatives in foods, beverages and pharmaceuticals. Sulfite is also endogenously generated during the metabolism of sulfur-containing amino acids and drugs. It has been shown that sulfite is a highly toxic molecule. Many studies have examined the effects of sulfite toxicity, but the effect of ingested sulfite on the number of neurons in the hippocampus has not yet been reported. The present study was undertaken to investigate the effect of ingested sulfite on pyramidal neurons by counting cells in CA1 and CA3-2 subdivisions of the rat hippocampus. For this purpose, rats were assigned to one of four groups (6 rats per group): control (C), sulfite (S), deficient (D) and deficient+sulfite (DS). Sulfite oxidase deficiency was established by feeding rats a low molybdenum diet and adding 200ppm tungsten (W) to their drinking water. Sulfite (70mg/kg) was also administered to the animals via their drinking water. At the end of the experimental period, the rats were sacrificed by exsanguination under anesthesia, and their brains and livers quickly removed. The livers were used for a SOX activity assay, and the brains were used for neuronal counts in a known fraction of the CA1 and CA3-2 subdivisions of the left hippocampus using the optical fractionator method, which is a stereological method. The results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA3-2) in the S, D and DS groups compared with the control group. It is concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA3-2 subdivisions in both normal and SOX deficient rat hippocampus. This finding provides supporting evidence that sulfite is a neurotoxic molecule.

Expression of URG4/URGCP, Cyclin D1, Bcl-2, and Bax genes in retinoic acid treated SH-SY5Y human neuroblastoma cells

Retinoic acid (RA) plays important roles in development, growth, and differentiation by regulating the expression of its target genes. The pro-apoptotic Bax gene may form channels through oligomerization in the mitochondrial membrane and facilitate the cytosolic release of cytochrome c. The anti-apoptotic Bcl-2 gene can inhibit this process. Up-regulated gene 4/Upregulator of cell proliferation (URG4/URGCP) is a novel gene located on 7p13. URG4/URGCP also stimulates cyclin D1 (CCND1) mRNA expression, and RNAi-mediated URG4/URGCP silencing diminishes CCND1 mRNA expression in HepG2 cells. In this study, the effects of RA treatment on URG4/URGCP, CCND1, Bcl-2 and Bax gene expression changes in undifferentiated and differentiated SHSY5Y neuroblastoma cells was analyzed. SHSY5Y cells were cultured in the appropriate conditions. To induce differentiation, the cells were treated with 10 micromolar RA in the dark for 3-10 days. SHSY5Y cells possess small processes in an undifferentiated state, and after treatment with RA, the cells developed long neurites, resembling a neuronal phenotype. Total RNA was isolated with Tri-Reagent. Expression profiles of the target genes were determined by semi-quantitative RT-PCR. According to the results, Bcl-2 and CCND1 gene expression levels were increased, while URG4/URGCP and Bax gene expression was decreased in RA treated cells compared to the control cells. Our preliminary results suggest that RA may induce cell proliferation and escape apoptosis using a novel pathway by the URG4/URGCP gene. Further investigations are needed to clarify more direct transcriptional targets of RA signaling and the interaction of RA pathways with other pro-regenerative signals.

Spinal reflexes in normal and sulfite oxidase deficient rats: effect of sulfite exposure:

Sulfites, which are commonly used as food preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). Although sulfite treatment has been reported to increase the excitability of some neurons in vitro, the possible effects of sulfite on neuronal excitability in vivo remain unclear. The aim of this study was to investigate the possible effects of sulfite treatment on spinal reflexes in anesthetized SOX competent and deficient rats. For this purpose, male albino rats used in this study were divided into four groups such as control group (C), sulfite group (CS), SOX deficient group (D), and SOX deficient + sulfite group (DS). Rats in SOX deficient groups were made deficient in SOX by the administration of low molybdenum (Mo) diet (AIN 76, Research Dyets Inc., USA) with concurrent addition of 200-ppm tungsten (W) to their drinking water in the form of sodium tungstate (NaWO4). Sulfite in the form of sodium metabisulfite (Na2O5S2, 70 mg/kg) was given orally by adding to drinking water to the S and DS groups. Monosynaptic reflex potentials were recorded from the ipsilateral L5 ventral root. SOX deficient rats had an approximately 15-fold decrease in hepatic SOX activity compared with normal rats. This makes SOX activity of SOXD rats in the range of human SOX activity. The results of this study show that sulfite treatment significantly increases the amplitude of the monosynaptic reflex response in both S and DS groups with respect to their respective control groups (C and D). SOX deficient rats also had enhanced spinal reflexes when compared with control rats. In conclusion, sulfite has increasing effects on the excitability of spinal reflexes and we speculate that this compound may exhibit its effects on nervous system by affecting sodium channels.

Effect of Sulfite Treatment on Erythrocyte Deformability in Young and Aged Rats

It is known that aging is associated with marked effects on integrity and function of cell membrane. These effects may also be exacerbated by exogenous chemicals, e.g. sulfite. Thus, the aim of this paper is to examine the influence of sulfite on hemorheological and related hematological parameters in rats of various ages. In this study, male Wistar rats at the age of 3 and 18 months were used and the following parameters were evaluated: Mean Cell Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), Red blood Cell (RBC) deformability and aggregation. The results show that aging is associated with a decrease in RBC deformability and MCHC, an increase in MCV. Sulfite administration significantly increased RBC deformability in both young and aged rats. Although MCHC was decreased in young rats, it was increased in aged rats in response to sulfite exposure. Additionally, sulfite induced a decrement in MCV of aged rats. Neither aging nor sulfite treatment caused significant alterations in RBC aggregation parameters in all experimental groups. In conclusion, these findings suggest that RBC deformability impairs with age and sulfite has ameliorating effects on RBC deformability in both young and aged rats.