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).
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).
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).
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.
It has been suggested that the adenosinergic system and cytokines play a role in the pathogenesis of epilepsy. Although the role of the adenosinergic system in the modulation of seizure activity is ...well known, the mechanism of this modulation needs to be described in detail. We performed this study to determine the contribution of the proinflammatory cytokines to the generalized seizure activity during adenosine and caffeine treatment.
We induced generalized tonic-clonic seizures with the administration of 60 mg/kg pentylenetetrazole (PTZ) in male Wistar Albino rats. Adenosine (500 mg/kg) or caffeine (5 mg/kg) was administered before PTZ injection. We monitored seizure activity and then determined the TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions of rats by ELISA.
Adenosine pretreatment significantly extended seizure latency (p < 0.05), but did not affect seizure duration and entry time to stage 4 seizure. Caffeine pretreatment did not change seizure latency and seizure duration. PTZ treatment did not change brain cytokine levels significantly (p > 0.05) compared to the control group. Whereas adenosine pretreatment decreased brain TNF-α, IL-1β, and IL-6 levels significantly (p < 0.05), caffeine pretreatment reduced brain cytokine levels slightly but nonsignificantly (p > 0.05).
Our results show that there is a clear relation between adenosinergic system and brain tissue cytokine levels. Our findings indicated that TNF-α, IL-1β, and IL-6 participate in the pathogenesis of generalized seizures, and the inhibition of TNF-α, IL-1β, and IL-6 with adenosinergic modulation may decrease seizure severity.
The Endoplasmic Reticulum (ER) is associated with many cellular functions, from post-transcriptional modifications to the proper folding of proteins, and disruption of these functions causes ER ...stress. Although the relationship between epileptic seizures and ER stress has been reported, the contribution of ER stress pathways to epileptogenesis is still unclear. This study aimed to investigate the possible effects of ER stress-related molecular pathways modulated by mild- and high-dose Thapsigargin (Tg) on absence epileptic activity, CACNA1H and immune responses in WAG/Rij rats. For this purpose, rats were divided into four groups; mild-dose (20 ng) Tg, high-dose (200 ng) Tg, saline, and DMSO and drugs administered intracerebroventriculary. EEG activity was recorded for 1 h and 24 h after drug administration following the baseline recording. In cortex and thalamus tissues, GRP78, ERp57, GAD153 protein changes (Western Blot), Eif2ak3, XBP-1, ATF6, CACNA1H mRNA expressions (RT-PCR), NF-κB and TNF-α levels (ELISA) were measured. Mild-dose-Tg administration resulted in increased spike-wave discharge (SWD) activity at the 24th hour compared to administration of saline, and high-dose-Tg and it also significantly increased the amount of GRP78 protein, the expression of Eif2ak3, XBP-1, and CACNA1H mRNA in the thalamus tissue. In contrast, high-dose-Tg administration suppressed SWD activity and significantly increased XBP-1 and ATF6 mRNA expression in the thalamus, and increased NF-κB and TNF-α levels. In conclusion, our findings indicate that Tg affects SWD occurrence by modulating the unfolded protein response pathway and activating inflammatory processes in a dose-dependent manner.
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•Tg affects SWD occurrence by modulating neuronal survival and pro-apoptotic processes of unfolded protein response in a dose-dependent manner.•Mild-dose of Tg-induced ER stress may have increased SWD activity through CACNA1H by inducing GRP78 and PERK neuronal survival pathways.•New generation small chaperones that affect ER stress pathways may contribute to discovering new treatment options for the absence epilepsy.
GDF15, hepcidin and mitoferrin-1 (mfrn-1) are proteins involved in systemic iron regulation. There are no studies in the literature demonstrating the serum mfrn-1 levels in polycythemia vera (PV) and ...essential thrombocythemia (ET) patients. The aim of this study was to investigate GDF15, hepcidin and mfrn-1 levels in PV and ET patients.
Ten PV, 17 ET patients, and 27 healthy controls (HCs) were enrolled. GDF15, hepcidin and mfrn-1 values were measured with enzyme-linked immunosorbent assay (ELISA).
GDF15 levels were higher in the myeloproliferative neoplasm (MPN) group (P = 0.002). Hepcidin levels were not different between MPN patients and HCs. The mfrn-1 levels were lower in MPN patients (P = 0.039). Hepcidin, GDF15, and mfrn-1 levels were not different between PV and ET patients. mfrn-1 levels were lower in ET patients than HCs (P = 0.038).
Increased erythropoiesis in MPNs may lead to high GDF15 levels in these patients. However, hepcidin was not suppressed despite the increased GDF15 levels and erythropoiesis in these patients. Decrease in mfrn-1 in MPNs can be the result of its increased turnover due to increased myelopoiesis. It can be hypothesized that similar hepcidin levels in patients and controls and low mfrn-1 levels in patients may be a defense mechanism against erythroid activity and thromboembolic complications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen ...sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats.
24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56 µmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA).
There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p<0.005). Also, there was significantly increase of NO and MDA levels and decrease of GSH levels in group 3 compared to other groups (p<0.005).
hydrogen sulfide prevents kidney damage with antioxidant and antiinflammatory effect.
Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a ...wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED.
All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for > 1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated.
The mean age of patients in ED group was 60.4 ± 11.3 years and 55.4 ± 9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5 ± 38.3 and 132.5 ± 53.3 ng/ mL, respectively, P < 0.001). The IGF-1 levels were positively correlated with ED score (r = 0.623, P < 0.01).
In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.
Abstract
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Epilepsy is a major pathological condition, characterized by recurrent seizures and affecting approximately 1% of the population. Many studies have shown a relationship between epilepsy and ...inflammation. The adenosinergic system contributes to inflammation and epilepsy by regulating the release of neurotransmitters through its various receptors. This study investigates the effect of agonist and antagonist of adenosinergic system on seizure activity and cytokine levels in the WAG/Rij strain, a genetic animal model of absence epilepsy.
The WAG/Rij rats used in our study were assigned to saline, Tween 20, adenosine, and caffeine groups. Tripolar electrodes were implanted on the skull, and EEG activities recorded for 3 h. ELISA was used to determine the NFkB, TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions, as well as the TNF-α, IL-1β, and IL-6 levels in the blood samples.
Administration of caffeine to rats resulted in a decreased SWD number at 30 and 60 min as determined by EEG recording after baseline (p < .05), and a significant increase in NFkB and IL-6 levels in the thalamic tissue (p < .05). Administration of adenosine to rats did not change seizures and cytokine levels.
Our results show that an increase in thalamic IL-6 and NFkB levels may related with a decrement in absence epilepsy. This study clearly shows the contribution of adenosinergic system in absence seizure in WAG/Rij rats. These results also support the importance of the thalamus on occurrence of SWD in the thalamocortical loop.
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•Caffeine treatment increased IL-6 and NFkB levels in thalamus tissue and IL-1β and TNF-α levels in serum.•An increase in thalamic IL-6 and NFkB levels induced a decrement in absence seizure.•Low-dose acute caffeine administration has an proinflammatory effect in the systemic circulation, however, an anti-inflammatory effect in the thalamic tissue.•The observed decrement in SWD was apparent at first hour in post-injection of caffeine.•This study supports the importance of the thalamus on occurrence of SWD in the thalamocortical loop.
Objective: Chronic stress is a factor that affects organs/tissues and disrupts homeostasis. This condition can lead to increased oxidative stress, which damages cellular components. Antioxidants ...attempt to prevent this damage by neutralizing free radicals. Our study aimed to investigate the effect of chronic mild stress on the levels of Catalase (CAT), Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Malondialdehyde (MDA) in serum and liver tissue. Material and Method: In our study, 16 Wistar albino rats were divided into control and experimental groups. The chronic unpredictable mild stress (CUMS) model protocol was employed. The levels of CAT, SOD, GPx, and MDA in serum and liver tissue were measured using the Enzyme-Linked Immunosorbent Assay method. Result: Upon comparison of serum CAT, SOD, GPx, and MDA levels, no statistically significant difference was observed between the control and stress groups (p>0.05). However, when comparing CAT, SOD, GPx, and MDA levels in the liver tissue, a significant increase in the levels of antioxidant enzymes was noted in the stress group (p<0.05). Conclusion: Under chronic stress, liver tissue's antioxidant levels appear to increase. We believe our study may contribute to understanding the connection between stress, free radicals, and antioxidants. Keywords: Antioxidant, chronic stress, oxidative stress Amac: Kronik stres, organ/dokulari etkileyen ve homeostazisi bozan bir faktordur. Bu durum, hucresel bilesenlere zarar veren oksidatif stresin artmasina neden olabilir. Antioksidanlar ise serbest radikalleri notralize ederek bu zarari onlemeye calisir. Calismamizin amaci, kronik hafif stresin serum ve karaciger dokusundaki Katalaz (CAT), Superoksit Dismutaz (SOD), Glutatyon Peroksidaz (GPx) ve Malondialdehit (MDA) seviyeleri uzerindeki etkisini arastirmaktir. Gerec ve Yontem: Calismamizda 16 Wistar albino sican kontrol ve deney gruplarina ayrilmistir. Kronik ongorulemeyen hafif stres model protokolu uygulandi. Serum/karaciger CAT, SOD, GPx ve MDA duzeyleri Enzyme Linked Immunosorbent Assay metodu ile olculdu. Bulgular: CAT, SOD, GPx ve MDA serum duzeyleri karsilastirildiginda kontrol ve stres gruplari arasinda istatistiksel olarak anlamli fark belirlenmedi (p>0,05). Buna karsin, karaciger dokularindaki CAT, SOD, GPx ve MDA seviyeleri karsilastirildiginda, stres grubunda antioksidan enzim seviyelerinde anlamli yukselis belirlenmistir (p<0,05). Sonuc: Kronik stres altinda, antioksidan enzim seviyelerinin karaciger dokusunda arttigi gorulmektedir. Calismamizin stres, serbest radikaller ve antioksidanlar arasindaki baglantiya yonelik bir katki sunabilecegi kanisindayiz. Anahtar Kelimeler: Antioksidan, kronik stres, oksidatif stress
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