Effect of penicillin G-induced epileptic seizures on hemorheological parameters in rats.

Normally, cerebral blood flow (CBF) is quantitatively coupled to cerebral metabolic rate like other tissues and maintained basically by altering vascular geometry and appropriate perfusion pressure. However, the rheological properties of the blood are important factors for effective tissue perfusion. Although a lot of studies have reported that hemorheological parameters are affected by a wide range of pathophysiological conditions, to our knowledge no research related to the effects of epileptic seizures on hemorheological parameters has been carried out. Thus, the aim of this study was to explore possible changes in rheological parameters including red blood cell (RBC) deformability, rigidity and aggregation, whole blood and plasma viscosity during epileptic seizures induced by penicillin G in rats. Eighteen female albino rats were divided into three groups that included sham operated controls (Group S), epileptic group (Group E), intraperitoneal penicillin group (Group IPP). Epilepsy was induced by intracortical injections of penicillin G. Hemorheological studies had been carried out 3 h after the induction of epilepsy. Among the studied hemorheological parameters, only RBC deformability was found to be different in the E group compared to S group. Epileptic seizures led to an increase in RBC deformability in the E group. In conclusion, these results suggest that in addition to an increase in CBF, RBC deformability may also improve to better match brain metabolic demands during seizures

Visual evoked potentials in normal and sulfite oxidase deficient rats exposed to ingested sulfite.

Sulfite oxidase (SOX) is an essential enzyme in the pathway of the oxidative degradation of sulfur amino acids, and protects cells from sulfite (SO(3)(2-)) toxicity. Rats do not mimic responses seen in human, because of their relatively high SOX activity levels. Therefore, the present study used SOX deficient rats since they are a more appropriate model for studying sulfite toxicity. The aim of the study was to investigate the effect of sulfite exposure on visual evoked potentials (VEPs) and thiobarbituric acid reactive substances (TBARS) in normal and sulfite oxidase deficient rats. Rats were assigned to six groups (n=10 rats/group) as follows; control (C), sulfite (S), sulfite+vitamin E (SE), deficient (D), deficient+sulfite (DS) and deficient+sulfite+vitamin E (DSE). Sulfite oxidase deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten (W). Sulfite (25img/kg) was administered to the animals via their drinking water. At the end of the experimental period, flash visual evoked potentials were recorded, and TBARS, hepatic sulfite oxidase levels and plasma S-sulphonate concentrations were determined. Sulfite treatment caused a significant delay in P1, N1P2, and P3 components of VEPs in the S and DS groups compared with the C group. These prolonged mean latencies of VEP components were reversed by vitamin E treatment in SE and DSE groups. In addition, the mean latencies of P1 and P3 components were increased in SOX deficient groups compared with the C group. Lipid peroxidation was increased in the brain in S, D, DS and DSE groups compared with the control group. There were also significant increases in the retina TBARS levels of S and DS groups. Vitamin E caused a significant decrease in brain and retina TBARS levels of SE and DSE groups with respect to their corresponding controls. However, there were no important changes in amplitudes of other groups. In conclusion, our results showed that sulfite treatment caused an increase in the lipid peroxidation process that was accompanied by changes in VEPs. Furthermore, sulfite exposure resulted in greater lipid peroxidation and more electrophysiological alterations in the SOX deficient rats than in the control rats. Additionally, the reduction of all VEP latencies in the DSE group with respect to the DS group clearly indicated that vitamin E has the potential to prevent sulfite induced-VEP changes arising from dysfunction of the SOX enzyme

The effect of diabetes mellitus on active avoidance learning in rats: the role of nitric oxide.

BACKGROUND: Growing data report memory and other cognitive problems among individuals with diabetes mellitus. Nitric oxide may play a key role in many physiological and pathological situations. The aim was to investigate the role of NO in diabetes-induced changes in learning and lipid peroxidation. MATERIAL/METHODS: Six groups of 10 rats each were formed: control (C), diabetic (D), control+L-arginine (CA), diabetic+L-arginine (DA), control+L-NAME (CN), and diabetic+L-NAME (DN) groups. Experimental diabetes mellitus was induced by injection of streptozotocin (60 mg/kg body weight). 160 mg/kg/day L-arginine or 10 mg/kg/day L-NAME were injected intraperitoneally to the relevant groups for eight weeks. Active avoidance behavior was studied in the middle of the eighth week using an automated shuttle box. Brain and hippocampal nitrite levels were measured by a fluorometric method. TBARS levels were measured fluorometrically using 1,1,3,3-tetramethoxypropane as a standard. RESULTS: The active avoidance training indicated that diabetes was associated with learning impairment. Administration of L-NAME and L-arginine significantly impaired active avoidance performance compared with the control group. They also decreased glucose level in group DA compared with the diabetic group. Brain nitrite level was significantly different in the diabetic group; hippocampus nitrite level tended to be lower in the L-NAME groups than the diabetic and control groups, although L-arginine increased hippocampal and brain nitrite values in the CA group compared with control groups. Brain and hippocampal TBARS levels were significantly higher in diabetic than in control rats. CONCLUSIONS: Imbalance related to nitric oxide production may contribute to cognitive dysfunction in diabetes mellitus

Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats.

Sulfites, which are commonly used as 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). The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and SOX-deficient rats. For this purpose, male albino rats used in this study were divided into eight groups such as control group (C), sulfite group (25 mg/kg) (S), vitamin E group (50 mg/kg) (E), sulfite (25 mg/kg)+vitamin E group (50 mg/kg) (SE), SOX-deficient group (D), deficient+vitamin E group (50 mg/kg) (DE), deficient+sulfite group (25 mg/kg) (DS) and deficient+sulfite (25 mg/kg)+vitamin E group (50 mg/kg) (DSE). Sulfite-induced impairment of active avoidance learning in SOX-deficient rats but not in normal rats. Sulfite had no effect on hippocampus TBARS levels in SOX normal groups. In SOX-deficient rats, TBARS levels were found to be significantly increased with sulfite exposure. Vitamin E reversed the observed detrimental effects of sulfite in the SOX-deficient rats on their hippocampal TBARS but not on their active avoidance learning. In conclusion, sulfite has neurotoxic effects in sulfite oxidase deficient rats, but this effect may not depend on oxidative stress

Altitude training induced alterations in erythrocyte rheological properties: A controlled comparison study in rats

Altitude training is frequently used by athletes to improve sea-level performance. However, the objective benefits of altitude training are controversial. This study aimed to investigate the possible alterations in hemorheological parameters in response to altitude training. Sprague Dawley rats, were divided into 6 groups: live low-train low (LLTL), live high-train high (LHTH), live high-train low (LHTL) and their controls live high and low (LHALC), live high (LHC), live low (LLC). LHC and LHTH groups were exposed to hypoxia (15% O2, altitudes of 3000 m), 4 weeks. LHALC and LHTL were exposed to 12 hours hypoxia/normoxia per day, 4 weeks. Hypoxia was maintained by a hypoxic tent. The training protocol corresponded to 60-70% of maximal exercise capacity. Rats of training groups ran on treadmill for 20-30 min/day, 4 days/week, 4 weeks. Erythrocyte deformability of LHC group was increased compared to LHALC and LLC. Deformability of LHTH group was higher than LHALC and LLTL groups. No statistically significant alteration in erythrocyte aggregation parameters was observed. There were no significant relationships between RBC deformability and exercise performance. The results of this study show that, living (LHC) and training at altitude (LHTH) seems more advantageous in hemorheological point of view. © 2014 - IOS Press and the authors. All rights reserved

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

The renoprotective effects of mannitol and udenafil in renal ischemia-reperfusion injury model.

PURPOSE: The aim of this study was to investigate and compare the effects of udenafil and mannitol in an experimental renal ischemia-reperfusion (I/R) injury model. MATERIALS AND METHODS: A total of 64 female Wister Albino rats were used. Right nephrectomy was performed in all groups. In the control group; I/R injury was not performed. In the I/R group; left renal pedicle was clamped for 45 minutes and then underwent 60 minutes and 24 hours of reperfusion. In the mannitol group; 1 mL 20% mannitol was given intravenously 15 minutes before clamping. In the udenafil group; 10-mg/kg udenafil was given orally 1 hour before clamping. Creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, malondialdehyde, neutrophil gelatinase associated lipocalin (NGAL), histological examination and DNA damage (Comet Assay method) levels were compared in tissue, serum and urine samples. RESULTS: Udenafil had a better protective effect than mannitol according to biochemical parameters (Cr, BUN, Cr clearance, and NGAL levels) and histopathological findings when compared with the I/R group. In the Comet sampling analysis no significant difference was detected. CONCLUSIONS: Udenafil has a better renoprotective effect than mannitol against I/R injury and this effect supports more functional improvements. Further clinical trials are needed to demonstrate those effects and clinical utility of udenafil for that purpose in humans

Oxidative stress of crystalline lens in rat menopausal model.

PURPOSE: To evaluate lenticular oxidative stress in rat menopausal models. METHODS: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Group 3), and the remaining 10 rats were administered intraperitoneal streptozocin to induce diabetes mellitus (Group 4). Total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) measurements of the crystalline lenses were analyzed. RESULTS: The mean OSI was the lowest in group 1 and highest in group 4. Nevertheless, the difference between the groups was not statistically significant in terms of OSI (p >0.05). The mean TOS values were similar between the groups (p >0.05), whereas the mean TAC of group 1 was significantly higher than that of the other groups (p <0.001). CONCLUSIONS: Our results indicate that menopause may not promote cataract formation

Investigation of the effects of a sulfite molecule on human neuroblastoma cells via a novel oncogene URG4/URGCP.

AIM: The aim of this study is to determine the anticancer effect of sulfite on SH-SY5Y neuroblastoma cells in vitro conditions and elucidate underlying molecular mechanism of sulfite and explore its therapeutic activity. MAIN METHODS: In this study, cytotoxic effects of sulfite in SH-SY5Y cels were detected over time in a dose dependent manner with the IC50 doses ranging from 0.5 to 10 mM. Genotoxic effect of sulfite was shown by comet assay. IC50 doses in the SH-SY5Y cells were detected as 5 mM. Expression profiles of the target genes related to apoptosis and cell cycle control were determined by quantitative RT-PCR. Protein changes were determined by western blot analysis. KEY FINDINGS: URG4/URGCP, CCND1, CCND2, CDK4, CDK6, E2F4 and BCL-2 gene expression levels were significantly reduced and RB1, TP53, BAX, BID, CASP2, CASP3, CASP9 and DIABLO gene expressions were significantly increased in dose group cells. The mechanism of this result may be related to sulfite dependent inhibition of cell cycle at the G1 phase by down-regulating URG4/URGCP or CCND1, CDK4, CDK6 gene expression and stimulating apoptosis via the intrinsic pathway. Sulfite suppressed invasion and colony formation in SH-SY5Y cell line using matrigel invasion chamber and colony formation assay, respectively. SIGNIFICANCE: It is thought that sulfite demonstrates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis s, invasion, and colony formation on SH-SY5Y cells. Sulfite may be an effective agent for treatment of neuroblastoma as a single agent or in combination with other agents