IInvestigation of possible oxidative damage caused by formaldehyde exposure in the rat's heart and aorta tissue / Investigación de posible daño oxidativo causado por la exposición al formaldehído en el corazón de la rata y tejido de la aorta

SUMMARY: Formaldehyde (FA) is a toxic substance used frequently in the field of medicine as well as in many industrial areas. Especially people working in the field of anatomy, histology, and pathology are in high risk group because of the use of the FA. Studies showing the effects of FA on the cardiovascular system are few in number. The purpose of the present study was to investigate the effects of FA exposure, which we believe can cause oxidative stress, on the heart and aorta with various biochemical analyses. A total of 24 Wistar Albino rats were used in our study. We divided the rats into 3 groups as the Control Group (CG), the group exposed to low-dose FA (avg. 1 ppm) (DDG) Group, and the group exposed to high-dose FA (avg. 10 ppm) (YDG). At the end of the subchronic FA exposure, the blood samples, heart and aorta tissues of the rats were taken and subjected to biochemical analyses. As a result of the analyses, statistically significant differences were detected between CG (2.96?0.85 ng/mg), and HDG (2.08?0.77 ng/mg) in aortic tissues in TXNIP analysis (p<0.05). In heart tissues, significant differences were detected between CG (0.73?0.27 ng/mg) and LDG (1.13?0.22 ng/mg) (p<0.05). Statistically significant differences were also detected between CG (1.98?0.31 mM/ml) and YDG (2.43?0.31 mM/ml) in serum MDA analyses (p<0.05). It was shown that subchronic application of FA to LDG rats through inhalation had no effects on apoptosis markers in heart tissues. More studies are required to show FA toxicity and the mechanism of action of pathology on the cardiovascular system. We believe that our study will contribute to clarifying the roles of mild and subchronic exposure of FA in heart and aortic tissues in terms of oxidative stress risk.

RESUMEN: El formaldehído es una sustancia tóxica que se utiliza con frecuencia en el campo de la medicina, así como en muchas áreas industriales. Especialmente las personas que trabajan en el area de la anatomía, y patología se encuentran en el grupo de alto riesgo debido al uso de esta sustancia. Pocos son los estudios que muestran los efectos del formaldehído en el sistema cardiovascular. El propósito del presente estudio fue investigar a través de análisis bioquímicos, los efectos de la exposición a formaldehído, que podría causar estrés oxidativo, en el corazón y la aorta. Se utilizaron un total de 24 ratas Albinas Wistar. Dividimos a las ratas en 3 grupos: grupo control (GC), grupo expuesto a dosis bajas de AG (promedio 1 ppm) (DDG) y grupo expuesto a dosis altas de AG (promedio 10 ppm) (YDG). Al término de la exposición a FA subcrónica, se tomaron muestras de sangre, tejido cardíaco y aorta de las ratas y se sometieron a análisis bioquímicos. Como resultado de los análisis, se detec- taron diferencias estadísticamente significativas entre GC (2,96 ? 0,85 ng / mg) y HDG (2,08 ? 0,77 ng / mg) en los tejidos aórticos en el análisis TXNIP (p <0,05). En los tejidos cardíacos se detectaron diferencias significativas entre GC (0,73 ? 0,27 ng / mg) y LDG (1,13 ? 0,22 ng / mg) (p <0,05). También se detectaron diferencias estadísticamente significativas entre CG (1,98 ? 0,31 mM / ml) y YDG (2,43 ? 0,31 mM / ml) en los análisis de MDA en suero (p <0,05). Se demostró que la aplicación subcrónica de formaldehído a ratas LDG a través de la inhalación no tuvo efectos sobre los marcadores de apoptosis en los tejidos del corazón. Se requieren más estudios para demostrar la toxicidad de los AG y el mecanismo de acción de la patología en el sistema cardiovascular. Creemos que nuestro estudio contribuirá a aclarar las funciones de la exposición leve y subcrónica de formaldehído en los tejidos cardíacos y aórticos en términos de riesgo al estrés oxidativo.

Evaluation of serum and aqueous humor klotho levels in pseudoexfoliation syndrome, pseudoexfoliation and primary open-angle glaucoma.

PURPOSE: The aim of our study was to compare klotho in the serum and aqueous humor of patients with primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEXG) and pseudoexfoliation syndrome (PEX). MATERIALS AND METHODS: 18 POAG, 20 PEXG, 19 PEX and 20 control patients were included in our study. Aqueous humor and serum samples were collected at the time of cataract surgery. Samples were collected using enzyme-linked immunosorbent assay to evaluate the levels of Klotho protein. RESULTS: Klotho levels in the serum and aqueous humor of PEXG patients (34.45 ± 3.59, 0.20 ± 0.15 ng/ml), PEX (35.85 ± 4.26, 0.23 ± 0.20 ng/ml) patients and POAG patients (35.99 ± 3.73, 0.25 ± 0.20 ng/ml) were significantly lower than control group (40.14 ± 3.85, 0.53 ± 0.39 ng/ml) (PEXG, P < 0.001, P < 0.001; PEX, P = 0.002, P = 0.003; POAG, P = 0.006, P = 0.003, respectively). Both serum and aqueous levels of klotho in the PEXG and PEX patients were lower than POAG patients, but the difference did not reach statistical significance (PEXG & POAG P = 0.149, P = 0.696), (PEX & POAG P = 0.845, P = 0.775). CONCLUSION: Klotho levels in the serum and aqueous humor decreased in PEX, PEXG and POAG groups compared to control group, but the reduction was most significant in PEXG group.

Effects of leptin, ghrelin and neuropeptide y on spike-wave discharge activity and certain biochemical parameters in WAG/Rij rats with genetic absence epilepsy.

This study aimed to evaluate the effects of leptin, ghrelin and neuropeptide-Y on the development of nonconvulsive seizure activity and their role on combating oxidative stress and cytokines produced by the systemic immune response in the WAG/Rij rat model for genetic absence epilepsy. Current study showed that all three peptides aggravated spike wave discharges activity and affected the oxidative stress in WAG/Rij rats without any significant changes in the levels of IL-1ß, IL-6 and TNF-α except leptin that only induced an increment in the concentration of IL-1ß. Our results support the modulatory role of these endogenous peptides on absence epilepsy.

Comparison of Cilostazol and Naftidrofuryl in an Experimental Acute Ischemia-Reperfusion Model.

INTRODUCTION: Naftidrofuryl and cilostazol are drugs with proven efficacy in the treatment of claudication in peripheral vascular disease. In this experimental study, we evaluated the effects of naftidrofuryl and cilostazol in ischemia-reperfusion (IR) injury on various tissues. MATERIALS AND METHODS: 40 male albino Wistar rats (8-12 weeks old, 250-350 g.) are randomly divided into 4 groups: Control (Group 1), sham (group 2), cilostazol pre-treatment (group 3), naftidrofuryl pre-treatment (group 4). During 21 days placebo is given to group 2, 12 mg/kg/day cilostazol is given to group 3, 50 mg/kg/day naftidrofuryl is given to group 4 orally. Ischemia and reperfusion are induced at the lower hind limb in Groups 2, 3 and 4. Ischemic muscle, kidney, liver, heart, brain and blood samples are obtained. The total antioxidant capacity, oxidant levels and oxidative stress index are studied for each group. RESULTS: Both drugs have protective effects of remote organ injury following IR. Systemic effects are similar to each other, both have protective effects of IR injury. It showed no statistical significance in the total antioxidant capacity. Total oxidant levels are significantly affected by cilostazol in the heart (p < 0.01) and by naftidrofuryl in the liver (p < 0.01). The effect on oxidative stress was only significant with cilostazol on the heart (p < 0.01). CONCLUSION: Cilostazol and naftidrofuryl had beneficial effects in all tissues against tissue damage caused by IR injury. In ischemic muscle, kidney and heart cilostazol had improved outcomes comparing to naftidrofuryl. Naftidrofuryl had benefits over cilostazol in liver tissue.

Association of Serum Paraoxonase 1 Activities, Polymorphisms and Oxidative Stress in Breast Cancer Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM). METHODS: Our study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI). RESULTS: PON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p<0.001). TOS and OSI were statistically higher in BC patients than HV group (p<0.001). CONCLUSIONS: Our results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.

Effect of nitric oxide synthase inhibitors in acute lung injury due to blunt lung trauma in rats.

BACKGROUND: This study aims to investigate the effects of blunt lung trauma performed in experimental rat model on lung tissue and blood as well as proinflammatory cytokines, oxidant-antioxidant enzymes and histopathological parameters after Ngamma-nitro-L-arginine methyl ester and N-iminoethyl-L-ornithine administration. METHODS: The study included 50 adult male Wistar albino rats (weighing 350 to 400 g). Rats were randomly allocated into four groups. Except in the control, moderate-level pulmonary contusion was created in all other groups. Intraperitoneal saline solution was performed in groups 1 and 2, 25 mg.kg-1 Ngamma-nitro-L-arginine methyl ester in group 3, and 20 mg.kg-1 N-iminoethyl-L-ornithine in group 4. Blood and lung tissues were studied biochemically and histopathologically. RESULTS: Best outcomes were recorded statistically significantly in groups with administration of Ngamma-nitro-L-arginine methyl ester and N-iminoethyl-L-ornithine when malondialdehyde response, mucous and histopathological values were examined. Significant improvement was detected in superoxide dismutase values in the group with administration of competitive nitric oxide synthase inhibitor Ngamma-nitro-L-arginine methyl ester. Nitric oxide values were substantially decreased in N-iminoethyl-L-ornithine group, while no significance was detected. CONCLUSION: Free oxygen radicals and lipid peroxidation played a role in pulmonary contusion after blunt lung trauma. According to biochemical and histopathological outcomes, effects of inflammation were decreased and protective effects were formed with administration of both Ngammanitro- L-arginine methyl ester and N-iminoethyl-L-ornithine.

An evaluation of rivaroxaban and clopidogrel in a rat lower extremity ischemia-reperfusion model: An experimental study.

BACKGROUND: This study aims to compare clopidogrel and rivaroxaban against ischemia-reperfusion injury after a long reperfusion time and to investigate its effects on various tissues. METHODS: A total of 40 Wistar rats were included in the study and were randomly divided into four groups (n=10 per group). Groups were defined as follows: control (Group 1), sham (Group 2), clopidogrel pre-treatment (Group 3), and rivaroxaban pre-treatment (Group 4). Ischemia (6 h) and reperfusion (8 h) were induced at the lower hind limb in Groups 2, 3, and 4. The ischemic muscle, heart, kidney, liver, and plasma tissues of the subjects were obtained to test for the oxidant (malondialdehyde) and antioxidants (glutathione, superoxide dismutase, and nitric oxide). RESULTS: Malondialdehyde levels were significantly higher in the sham group, compared to the controls in all tissues. Clopidogrel and rivaroxaban pre-treatment significantly decreased malondialdehyde levels, compared to the heart, ischemic muscle, liver, and blood tissues of the sham group. Kidney malondialdehyde levels were reduced only by rivaroxaban. Group 4 had significantly decreased malondialdehyde levels, compared to Group 3 in ischemic muscle (p<0.010). The glutathione reduction, compared to sham group, in the kidney was only significant for Group 4 (p<0.050). With clopidogrel and rivaroxaban pretreatment, nitric oxide levels significantly decreased only in the heart tissue, compared to sham group (p<0.001 and p<0.050, respectively). CONCLUSION: The study results suggest that rivaroxaban and clopidogrel are effective in reducing ischemia-reperfusion injury in the heart, ischemic muscle, liver, and blood. Rivaroxaban also protects the kidneys and is superior to clopidogrel in ischemic muscle protection.

Differential diagnosis of Crohn's disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae.

BACKGROUND/AIMS: Glycoprotein 2 (GP2), the major autoantigen of Crohn's disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. MATERIALS AND METHODS: A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. RESULTS: Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. CONCLUSION: The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.

Decreased ERp57 Expression in WAG/Rij Rats Thalamus and Cortex: Possible Correlation with Absence Epilepsy.

BACKGROUND: The role of intracellular proteins in the pathogenesis of absence epilepsy were mentioned. These proteins are thought to be related to energy generation, signal transduction, inflammation processes and membrane conductance. OBJECTIVES: The investigation of protein profile of the genetically epileptic rat brains was the main subject of this study. METHODS: For this, a 2D-gel electrophoresis based comparative proteome analysis was performed using thalamus tissue of genetic absence epileptic WAG/Rij and age matched Wistar rats. Regulated spots displaying differences in their abundance were identified using MALDI-TOF/TOF. Among the six spots (DHRS9, BR44, HINT1, CREM, SPRE and PDIA3/ERp57) the highest mascot score was attributed to ERp57 a neuroprotective/neurodegenerative system associated protein. Western Blot analyses were performed to validate changes occurring at ERp57 in thalamus and also identify changes in fronto-parietal cortex. RESULTS: Reductions in the expression levels of ERp57 were detected in the thalamic and the fronto-parietal brain regions of the WAG/Rij rats in comparison to Wistar rats. CONCLUSION: Such difference might be associated with the pathogenic mechanisms dictating the absence epilepsy. Lower levels of ERp57 may be playing an important role in the development of spontaneous seizures activity seen in the absence epileptic WAG/Rij rats strain.

The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1ß, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model.

The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80µg/kg)+PTZ, and Group 5: NPY (60µg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1ß, IL-6, FGF-2, galanin, nitric oxide (NOÖ¹), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p<0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures.

Investigation of subclinical atherosclerosis in psoriatic arthritis patients with minimal disease activity.

The aim of this study was to investigate the presence of subclinical atherosclerosis among psoriatic arthritis (PsA) patients without any cardiovascular disease (CVD) or traditional cardiovascular risk factors through measurement of endothelial function and carotid intima-media thickness (IMT) and correlated with disease-related risk factors. Twenty patients with PsA according to classification criteria for psoriatic arthritis and 20 age- and sex-matched controls were included. Patients with risk factors for cardiovascular disease were excluded. Carotid IMT was measured using two-dimensional carotid ultrasonography (USG). Endothelial function was determined by measuring flow-mediated endothelial-dependent vasodilatation (FMD %) and nitrate-induced dilatation (NID %) using brachial artery USG. Additionally, serum asymmetric dimethylarginine (ADMA) level was obtained using ELISA methodology. In this cross-sectional study, FMD % was significantly more decreased among PsA patients versus control group [mean 11 % (median (range) %10.5 (8-15 %)] and mean 13.2 % [median (range) 12, 8 % (8.1-17.6 %), respectively; p = 0.01]. There was no significant difference in NID %, ADMA level and mean IMT or maximum IMT results. FMD % did not show a significant correlation with clinical and laboratory data of PsA patients. This study showed that endothelial dysfunction may be present in PsA patients with no CVD and traditional cardiovascular risk factors. The study findings lend support to the previous reports that suggested a potential relationship between PsA and atherosclerotic disorders.

The relationship between brain-derived neurotrophic factor levels, oxidative and nitrosative stress and depressive symptoms: a study on peritoneal dialysis.

BACKGROUND: Depression is one of the most commonly encountered psychiatric problems in peritoneal dialysis (PD) patients. Our aim was to investigate the associations between oxidative and nitrosative stress (O&NS) and brain-derived neurotrophic factor (BDNF) in PD patients with elevated depressive symptoms (EDS). METHODS: Eighty-three patients with PD and 84 healthy controls were enrolled in this study. In PD patients, two subgroups were formed: 28 with and 55 without EDS. EDS were defined as a Beck Depression Inventory (BDI) score ≥17 in patients. Serum malondialdehyde (MDA) erythrocyte, glutathione (GSH) levels measured spectrophotometrically. Serum superoxide dismutase (SOD) activity, nitric oxide (NO) and BDNF levels were determined by ELISA. RESULTS: While MDA and NO levels were higher, levels of SOD, GSH and BDNF were lower in PD patients compared to controls (p < 0.001). The patients with EDS had higher levels of MDA and lower levels of BDNF as compared to those without EDS (p < 0.005). In linear regression analysis, the BDNF levels were dependently associated with SOD levels in PD patients (B: 0.274, p: 0.043). In addition, while a negative correlation existed between BDI scores with BDNF levels (r = -0.312, p = 0.004), a positive correlation was present between BDI scores and MDA levels (r = 0.320, p = 0.005) in PD patients. CONCLUSION: Our results suggest the presence of high O&NS and low antioxidant capacity accompanied with decreased levels of BDNF in PD patients, especially those with EDS were deeper. These may represent the risk factors for cellular injury and might reveal part of the mechanism causing the depressive state in PD patients.

Effects of single-dose neuropeptide Y on levels of hippocampal BDNF, MDA, GSH, and NO in a rat model of pentylenetetrazole-induced epileptic seizure.

Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, which may increase the content of reactive oxygen and nitrogen species. The objective of this study was to investigate the effects of Neuropeptide Y on oxidative and nitrosative balance and brain-derived neurotrophic factor levels induced by pentylenetetrazole (a standard convulsant drug) in the hippocampus of Wistar rats. Three groups of seven rats were treated intraperitoneally as follows: group 1 (saline + saline) 1 ml saline, group 2 (salin + Pentylenetetrazole) 1 ml saline 30 min before Pentylenetetrazole; and group 3 (Neuropeptide Y + Pentylenetetrazole) 60 µg/kg Neuropeptide Y 30 min before 60 mg/kg Pentylenetetrazole. After 24 h, the animals were euthanized by decapitation. Hippocampus were isolated to evaluate the malondialdehyde, glutathione, nitric oxide, and brain-derived neurotrophic factor levels in three rat groups. The results of this study demonstrated that while intraperitoneally administered neuropeptide Y did not result in a statistically significant difference in BDNF levels, its administration caused a statistically significant decrease in malondialdehyde and nitric oxide levels and an increase in glutathione levels in rats with pentylenetetrazole-induced epileptic seizure. Neuropeptide Y were able to reduce nitroxidative damage induced by pentylenetetrazole in the hippocampus of Wistar rats.

The effects of vagal nerve stimulation in focal cerebral ischemia and reperfusion model.

AIM: This study aimed to investigate the effects of VNS in transient middle cerebral artery occlusion and reperfusion (MCAO/R) rat model of ischemia based on behavioral, morphological, and molecular approaches. MATERIAL AND METHODS: Wistar albino rats were divided into 3 groups: ischemia-reperfusion (I/R), I/R+VNS, and sham (for I/R). Each group was further divided into two subgroups for the assessment of neurological deficits and infarct area, or biochemical parameters related to oxidative stress. RESULTS: The infarct area and neurological scores were significantly lower in I/R+VNS group compared with the I/R group. MDA levels were significantly higher in I/R group compared to control and I/R+VNS groups in the cortical and subcortical specimens. There were also betweengroup differences in terms of GSH levels. GSH levels were higher in sham group compared with and I/R and I/R+VNS groups in cortical specimens whereas these levels for lower in I/R group compared to control and I/R+VNS groups in the subcortical specimens. SOD activity was higher in control group compared to I/R and I/R+VNS groups both in the cortical and subcortical specimens. There was no difference between I/R and I/R+VNS groups in neither cortical nor subcortical specimens. CONCLUSION: The neuroprotective and antioxidant properties of VNS suggest its efficacy as a potential anti-ischemic treatment.

Effects of carbamazepine on serum parathormone, 25- hydroxyvitamin D, bone specific alkaline phosphatase, C-telopeptide, and osteocalcin levels in healthy rats.

It is still not completely clear whether carbamazepine causes alterations in vitamin D status and in bone metabolism. The objective of this study was to investigate the effects of carbamazepine on serum levels of 25-hydroxyvitamin D and on biomarkers of bone formation and resorption in healthy rats. Levels of calcium, 25- hydroxyvitamin D, parathormone, C-telopeptide, bone specific alkaline phosphatase and osteocalcin were measured in 3 groups of rats consisting of controls (n=10), isotonic saline solution group (n=10) and carbamazepine group (n=10). Mean calcium levels were found to be significantly lower in healthy controls in comparison to isotonic saline solution and carbamazepine groups (10.0±0.24, 10.81±0.16, 10.93±0.22 mg/dL, respectively, p<0.05). Mean levels of 25- hydroxyvitamin D, were found to be significantly higher in control group compared to isotonic saline solution group (25- hydroxyvitamin D; 25.91±1.12, 19.99±0.99 ng/mL, respectively, p<0.01). Mean levels of parathormone and osteocalcin were found to be significantly higher in control group compared to isotonic saline solution group and carbamazepine group. Parathormone levels were measured as 3.46±0.83, 1.08±0.08, 0.94±0.02 pg/mL, respectively (p<0.01). Osteocalcine levels were measured as 1.66±0.001, 1.32±0.002, 1.32±0.001 ng/mL, respectively (p<0.001). A significant difference in terms of mean serum bone specific alkaline phosphatase and C-telopeptide levels among groups was not observed. The main outcome of this prospective study in healthy rats showed no change in biochemical parameters of bone turnover during treatment with carbamazepine.

Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice.

AIMS: Tianeptine is an atypical antidepressant drug that has a different mechanism of action than other antidepressants. Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia. The present study was undertaken to investigate effects of chronic administration of tianeptine or olanzapine on unpredictable chronic mild stress (UCMS)-induced depression-like behavior in mice compared to a widely used SSRI antidepressant, fluoxetine. MAIN METHODS: Male inbred BALB/c mice were subjected to different kinds of stressors several times a day for 7weeks and were treated intraperitoneally with tianeptine (5mg/kg), olanzapine (2.5mg/kg), fluoxetine (15mg/kg) or vehicle for 5weeks (n=7-8 per group). KEY FINDINGS: All the drugs tested prevented stress-induced deficit in coat state during UCMS procedure, in grooming behavior in the splash test, decreased the attack frequency in the resident intruder test and decreased the immobility time in the tail suspension test. In the open field test olanzapine had anxiolytic-like effects in both stressed and non-stressed mice. Tianeptine, olanzapine and fluoxetine decreased the enhanced levels of plasma ACTH and IL-6. Chronic treatment with tianeptine resulted in a significant increase in both total number and density of BrdU-labeled cells in stressed animals, while fluoxetine and olanzapine had a partial effect. SIGNIFICANCE: The results of this study support the hypothesis that tianeptine can be as effective as fluoxetine for the treatment of depression in spite of the differences in the mechanism of action of these drugs. Moreover, olanzapine could be used effectively in psychotic patients with depression.

Effects of chronic kidney disease and type of dialysis on serum levels of adiponectin, TNF-alpha and high sensitive C-reactive protein.

BACKGROUND: In uremic patients, depending on their type, the T-cells produce a range of pro-inflammatory and anti-inflammatory cytokines. The aim of this study was to compare the effects of chronic kidney disease (CKD) and two different therapy methods of dialysis [hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD)] on adiponectin, TNF-alpha, and hs-CRP levels in human serum. METHODS: We measured the serum levels of hs-CRP, adiponectin, and TNF-alpha in 37 patients with CKD on conservative treatment, 34 patients maintained on CAPD, 35 HD patients, and 25 healthy volunteers. The statistical analysis of the obtained results was performed by commercial statistics PC software. RESULTS: The mean TNF-alpha levels were found to be significantly higher in patients in the predialysis, CAPD, and the HD groups, than in the control group (17.24 +/- 9.22, 31.57 +/- 10.56, 24.34 +/- 5.32, 7.64 +/- 4.12 pg/mL, respectively, p < 0.001). The mean TNF-alpha levels in the predialysis group were significantly lower than in both the CAPD and the HD group (p < 0.001). The mean TNF-alpha levels in the CAPD group were significantly higher than in the HD group (p = 0.001). The mean adiponectin levels in the control group were significantly lower than in the predialysis, CAPD, and HD groups (2.54 +/- 2.30, 4.10 +/- 3.12, 7.69 +/- 8.35, 5.97 +/- 6.20 ng/mL, respectively, p < 0.05). Furthermore, the mean adiponectin levels in the predialysis groups were significantly lower than in the CAPD group (p < 0.05). The mean hs-CRP levels were found to be significantly higher in patients in the predialysis, CAPD, and HD groups than in the control group (0.65 +/- 0.57, 0.82 +/- 0.71, 1.14 +/- 1.45, 0.30 +/- 0.19 mg/dL, respectively, p < 0.05). CONCLUSIONS: According to the results of this study, the levels of adiponectin, hs-CRP, and TNF-alpha were increased for all patients with chronic renal failure (CRF). Along with this, the highest level of increase in TNF-alpha levels were observed in patients with CAPD.

Effect of pentylenetetrazole and sound stimulation induced single and repeated convulsive seizures on the MDA, GSH and NO levels, and SOD activities in rat liver and kidney tissues.

OBJECTIVES: the aim of our study was to evaluate the activity of superoxide dismutase (SOD) and the levels of glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) in liver and kidney tissues in a rat model of convulsive seizure induced by single and repeated doses of pentylenetetrazole (PTZ) and sound stimulation with key ringing. MATERIALS AND METHODS: male Wistar adult rats (n=48), were used in the experiment. The animals were divided into six groups: (1) Single Seizure Control Group (SS-Control; n=8), (2) Repeated Seizures Control Group (RS-Control; n=8), (3) PTZ induced Single Seizure Group (SS-PTZ Group; n=8), (4) PTZ induced Repeated Seizures Group (RS- PTZ Group; n=8), (5) Key-Ringing Induced Single Seizure Group (SS-KEY Group; n=8), (6) Key-Ringing Induced Repeated Seizures Group (RS-KEY Group; n=8). Following injections rats were observed for seizure activity for 30 min. Animals were sacrificed 24h after induced seizure (single or last seizure) or saline administration. MDA, NO, GSH levels and SOD activities were determined in liver and kidney tissues. RESULTS: there was no significant difference between SS-Control and RS-Control groups, SS-PTZ and SS-KEY groups, and RS-PTZ and RS-KEY groups (p>0.05) in none of the examined 4 parameters in liver and kidney tissues. The liver and kidney levels of MDA and NO in SS-PTZ group were found to be significantly higher than the SS-Control group (p<0.05). In SS-KEY group, the liver and kidney levels of MDA and NO were found to be significantly higher and GSH levels were significantly lower than the SS-Control group (p<0.05). While liver and kidney levels of MDA in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p<0.05), liver and kidney GSH levels were significantly lower (p<0.05). The liver levels of NO in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p<0.05). Kidney SOD activities in RS-PTZ group and RS-KEY group were found to be significantly lower than the RS-Control group (p<0.05). When RS-PTZ group is compared with the SS-PTZ group, the liver SOD activity and kidney NO level were found to be significantly lower in the RS-PTZ group (p<0.05). While the liver NO level and GSH level in RS-KEY group were significantly higher than the SS-KEY group, SOD activity was significantly lower in the RS-KEY group (p<0.05). When RS-KEY group was compared with SS-KEY group, the kidney NO level and SOD activity were found to be significantly lower in the RS-KEY group (p<0.05). CONCLUSION: in conclusion, key-ringing or PTZ induced single and repeated seizures result in increased oxidative damage and lipid peroxidation, and decreased antioxidant defense mechanisms.

Serum fetuin--a concentrations are inversely related to cytokine concentrations in patients with chronic renal failure.

BACKGROUND/AIMS: A close relationship exists between inflammation and vascular calcification. Although fetuin-A is known to be an inhibitor of calcification, studies correlating levels of this glycoprotein to markers of inflammation are limited. To understand these relationships, we investigated the relationship between serum fetuin-A and proinflammatory cytokine levels in patients with chronic renal failure (CRF). METHODS: Thirty-two patients on haemodialysis (HD), 32 conservatively managed chronic kidney disease (CKD) patients and a control group of 25 subjects with normal renal function were enrolled in this study. Serum fetuin-A, IL-1beta, IL-6 and TNF-alpha levels were measured by ELISA. Correlations between serum fetuin-A and IL-1beta, IL-6 and TNF-alpha concentrations were investigated by the Spearman correlation test. RESULTS: In 64 CRF patients (on HD and with CKD), serum fetuin-A was significantly and inversely related to IL-1beta (P<0.001), IL-6 (P=0.025) and TNF-alpha levels (P=0.007), respectively. The serum fetuin-A levels of the control subjects were not significantly correlated to levels of the inflammatory markers IL-1beta, IL-6 and TNF-alpha (P=0.551, 0.985 and 0.984, respectively). CONCLUSION: The negative correlation between serum fetuin-A and cytokine concentrations in CRF patients supports the hypothesis of inflammation-dependent down-regulation of fetuin-A expression.

Adipocytokines leptin and adiponectin, and measures of malnutrition-inflammation in chronic renal failure: is there a relationship?

BACKGROUND: Serum levels of adipocytokines such as leptin and adiponectin are significantly elevated in patients with chronic renal failure (CRF). The effect of such adipocytokines on malnutrition in the CRF population has been of substantial interest. We sought to determine the relationship between plasma leptin and adiponectin levels and malnutrition-inflammation status in end-stage renal disease patients. METHODS: Thirty patients (15 women and 15 men; mean [+/-SD] age, 50 +/- 14 years) on hemodialysis, and 30 patients (12 women and 18 men; mean [+/-SD] age, 47 +/- 16) on continuous ambulatory peritoneal dialysis, were enrolled in this study. Adipocytokine levels were measured by enzyme-linked immunosorbent assay. Inflammatory markers, such as high-sensitivity serum C-reactive protein (hs-CRP), ferritin, and a nutritional inflammatory scoring system known as the malnutrition-inflammation score (MIS), were also measured in all patients. RESULTS: Serum leptin had negative correlations with ferritin (r = -0.33, P = .016) and MIS (r = -0.39, P = .003). Adiponectin had a weak positive correlation with MIS (r = 0.26, P = .050), indicating that an increased level of serum adiponectin was associated with a worse nutritional status. Levels of hs-CRP, serum albumin, cholesterol, and triglycerides did not correlate with nutritional status. CONCLUSIONS: Serum leptin concentration seems to be a marker of good nutritional status, rather than an appetite-suppressing uremic toxin, in patients with CRF. However, the positive correlation between serum adiponectin and worse nutritional-inflammatory status suggests that elevated adiponectin levels may contribute to the pathogenesis of malnutrition in such patients.