Hakan Er

Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxiredoxin 6 (Prdx6) proteins in healthy and pathologic placentas of human and rat

A relationship has been shown between preeclampsia (PE) and intrauterine growth restriction (IUGR) and oxidative stress (OS). Since such pregnancies experience OS, we aimed to detect the distribution pattern and expression levels of a transcription factor, Nuclear factor erythroid 2-related factor-2 (Nrf2) that has a role in the regulation of antioxidant enzymes, and peroxiredoxin 6 (Prdx6) an antioxidant enzyme, in human healthy, IUGR, PE and in groups of rat healthy and IUGR placentas using immunohistochemistry and Western blotting. Both Nrf2 and Prdx6 immunoreactivities were weaker in human and rat IUGR group placentas compared to human and rat control group placentas, respectively. Nrf2 and Prdx6 were immunostained in labyrinth trophoblasts, decidua, giant, glycogen and fetal vessel endothelial cells in rat control and IUGR group placentas. Nrf2 and Prdx6 immunoreactivities were seen in the decidua, syncytiotrophoblasts, villous stromal cells, and vascular endothelium in human control, IUGR and PE group placentas. Results of Nrf2 and Prdx6 Western blotting applied for rat and human placentas were compatible with the results of Nrf2 and Prdx6 immunohistochemical observations with regard to rat and human placentas. Down-regulation of Nrf2 and Prdx6 proteins in human and rat IUGR group placentas may have led to the formation of OS which may have impaired proliferation and invasion of cytotrophoblasts.

Effects of rosmarinic acid on cognitive and biochemical alterations in ovariectomized rats treated with D-galactose

INTRODUCTION Animal models designed to mimic certain features of Alzheimers disease (AD) can help us to increase our understanding of the underlying mechanisms of disease. Previous studies have revealed that long-term D-galactose injection combined with ovariectomy results in pathophysiologic alterations associated with AD. Thus, the aim of the present study was to investigate the effects of rosmarinic acid (RA) administration on pathological changes associated with ovariectomy and D-galactose injection, which serve as a two-insult model for AD. MATERIAL AND METHODS One hundred female Wistar rats were divided into five equal groups: control (C), Sham (Sh), rosmarinic acid treated (R), ovariectomized rats treated with D-galactose (OD), ovariectomized rats treated with D-galactose and rosmarinic acid (ODR) groups. D-galactose (80 mg/kg/day) was administered by i.p. injection and RA (50 mg/kg/day) was given via gavage for 60 days. Open field and Y-maze tests were used to assess locomotor activity and short-term spatial memory, respectively. Biochemical and histopathological analyses of the brain tissue were performed. RESULTS Open field testing showed that the locomotor activity and exploratory behavior of rats were prominently impaired in the OD group as compared to the other studied groups. Similarly, Y-maze test results revealed a decrease of short-term spatial memory in the OD rats. A concomitant treatment with RA significantly restored altered locomotor activity and cognitive functions in the ODR group. Lipid peroxidation levels, cyclooxygenase-2 expression and prostaglandin E2 levels in the brain tissue were higher in the OD group and RA treatment inhibited these changes. AD-like histopathological alterations and amyloid b peptide (Ab) depositions were observed in the OD group. Normal cell structure and lower Ab depositions were observed in the ODR group compared with the OD group. CONCLUSIONS RA could have the potential to prevent some psychological and biochemical alterations of brain tissue found in a rat model of AD probably by attenuating lipid peroxidation and inflammatory response.

2100-MHz electromagnetic fields have different effects on visual evoked potentials and oxidant/antioxidant status depending on exposure duration.

The purpose of the present study was to investigate the duration effects of 2100-MHz electromagnetic field (EMF) on visual evoked potentials (VEPs) and to assess lipid peroxidation (LPO), nitric oxide (NO) production and antioxidant status of EMF exposed rats. Rats were randomized to following groups: Sham rats (S1 and S10) and rats exposed to 2100-MHz EMF (E1 and E10) for 2h/day for 1 or 10 weeks, respectively. At the end of experimental periods, VEPs were recorded under anesthesia. Brain thiobarbituric acid reactive substances (TBARS) and 4-hydroxy-2-nonenal (4-HNE) levels were significantly decreased in the E1 whereas increased in the E10 compared with their control groups. While brain catalase (CAT), glutathione peroxidase (GSH-Px) activities and NO and glutathione (GSH) levels were significantly increased in the E1, reduction of superoxide dismutase (SOD) activity was detected in the same group compared with the S1. Conversely, decreased CAT, GSH-Px activities and NO levels were observed in the E10 compared with the S10. Latencies of all VEP components were shortened in the E1 compared with the S1, whereas latencies of all VEP components, except P1, were prolonged in the E10 compared with the S10. There was a positive correlation between all VEP latencies and brain TBARS and 4-HNE values. Consequently, it could be concluded that different effects of EMFs on VEPs depend on exposure duration. In addition, our results indicated that short-term EMF could provide protective effects, while long-term EMF could have an adverse effect on VEPs and oxidant/antioxidant status.

Effects of acute and chronic exposure to both 900 MHz and 2100 MHz electromagnetic radiation on glutamate receptor signaling pathway

Abstract Purpose: To demonstrate the molecular effects of acute and chronic exposure to both 900 and 2100 MHz radiofrequency electromagnetic radiation (RF-EMR) on the hippocampal level/activity of some of the enzymes – including PKA, CaMKIIα, CREB, and p44/42 MAPK – from N-methyl-D-aspartate receptor (NMDAR)-related signaling pathways. Materials and methods: Rats were divided into the following groups: sham rats, and rats exposed to 900 and 2100 MHz RF-EMR for 2 h/day for acute (1 week) or chronic (10 weeks), respectively. Western blotting and activity measurement assays were used to assess the level/activity of the selected enzymes. Results: The obtained results revealed that the hippocampal level/activity of selected enzymes was significantly higher in the chronic groups as compared to the acute groups at both 900 and 2100 MHz RF-EMR exposure. In addition, hippocampal level/activity of selected enzymes was significantly higher at 2100 MHz RF-EMR than 900 MHz RF-EMR in both acute and chronic groups. Conclusions: The present study provides experimental evidence that both exposure duration (1 week versus 10 weeks) and different carrier frequencies (900 vs. 2100 MHz) had different effects on the protein expression of hippocampus in Wistar rats, which might encourage further research on protection against RF-EMR exposure.

Determination of PCNA, cyclin D3, p27, p57 and apoptosis rate in normal and dexamethasone-induced intrauterine growth restricted rat placentas

Intrauterine growth restriction (IUGR) is a major clinical problem, which causes perinatal morbidity and mortality. One of the reasons for IUGR is abnormal placentation. In rats, fetal-placental exposure to maternally administered glucocorticoids decreases birth weight and placental weight. Proper placental development depends on the proliferation and differentiation of trophoblasts. Our knowledge about the mitotic regulators that play key roles in synchronizing these events is limited. Also the mechanisms underlying the placental growth inhibitory effects of glucocorticoids have not been elucidated. The aim of this study was to investigate the immunolocalization, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin D3, p27 and p57 in normal and dexamethasone-induced IUGR Wistar rat placentas by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and Western blot. We also compared apoptotic cell numbers at the light microscopic level via terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and transmission electron microscopy. Glucocorticoid levels were higher in IUGR rats than in control rats after 60 and 120min of injection. We showed reduced gene and protein expressions of PCNA and cyclin D3 and increased expressions of p27 and p57 in IUGR placentas compared to control placentas. Apoptotic cell number was higher in the placentas of the IUGR group. In brief we found that maternal dexamethasone treatment led to a shift from cell proliferation to apoptosis in IUGR placentas. Dexamethasone induced placental and embryonal abnormalities which could be associated with reduced expressions of PCNA and cyclin D3, increased expressions of p27 and p57 and increased rate of apoptosis in IUGR placentas.

Protective role of rosmarinic acid on amyloid beta 42-induced echoic memory decline: Implication of oxidative stress and cholinergic impairment

ABSTRACT In the present study, we examined whether rosmarinic acid (RA) reverses amyloid &bgr; (A&bgr;) induced reductions in antioxidant defense, lipid peroxidation, cholinergic damage as well as the central auditory deficits. For this purpose, Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR), A&bgr;42 peptide (A&bgr;) and A&bgr;42 peptide + RA (A&bgr;R) groups. Rat model of Alzheimer was established by bilateral injection of A&bgr;42 peptide (2,2 nmol/10 &mgr;l) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by gavage for 14 days after intracerebroventricular injection. At the end of the experimental period, we recorded the auditory event related potentials (AERPs) and mismatch negativity (MMN) response to assess auditory functions followed by histological and biochemical analysis. A&bgr;42 injection led to a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and 4‐Hydroxy‐2‐nonenal (4‐HNE) but decreased the activity of antioxidant enzymes (SOD, CAT, GSH‐Px) and glutathione levels. Moreover, A&bgr;42 injection resulted in a reduction in the acetylcholine content and acetylcholine esterase activity. RA treatment prevented the observed alterations in the A&bgr;R group. Furthermore, RA attenuated the increased A&bgr; staining and astrocyte activation. We also found that A&bgr;42 injection decreased the MMN response and theta power/coherence of AERPs, suggesting an impairing effect on auditory discrimination and echoic memory processes. RA treatment reversed the A&bgr;42 related alterations in AERP parameters. In conclusion, our study demonstrates that RA prevented A&bgr;‐induced antioxidant‐oxidant imbalance and cholinergic damage, which may contribute to the improvement of neural network dynamics of auditory processes in this rat model. HighlightsA&bgr;42 affects antioxidant‐oxidant balance and cholinergic system.A&bgr;42 causes deficit in network dynamics of auditory system.Rosmarinic acid reverses the A&bgr;42 induced alterations in auditory functions.Cholinergic enhancement via rosmarinic acid might be useful in AD.Rosmarinic acid might be efficient in AD treatment with its multiple bioactivities.

Changes of auditory event-related potentials in ovariectomized rats injected with d-galactose: Protective role of rosmarinic acid

HIGHLIGHTSOvariectomy alone and with d‐galactose treatment affected the auditory processing.Estrogen deficiency and d‐galactose induce lipid peroxidation.Rosmarinic acid reversed the AERP/MMN alterations in OVX d‐galactose injected rats. ABSTRACT Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful agent for protecting central nervous system against age related alterations. In this context, the purpose of the present study was to investigate possible protective effects of RA on mismatch negativity (MMN) component of auditory event‐related potentials (AERPs) as an indicator of auditory discrimination and echoic memory in the ovariectomized (OVX) rats injected with d‐galactose combined with neurochemical and histological analyses. Ninety female Wistar rats were randomly divided into six groups: sham control (S); RA‐treated (R); OVX (O); OVX + RA‐treated (OR); OVX + d‐galactose‐treated (OD); OVX + d‐galactose + RA‐treated (ODR). Eight weeks later, MMN responses were recorded using the oddball condition. An amplitude reduction of some components of AERPs was observed due to ovariectomy with or without d‐galactose administiration and these reduction patterns were diverse for different electrode locations. MMN amplitudes were significantly lower over temporal and right frontal locations in the O and OD groups versus the S and R groups, which was accompanied by increased thiobarbituric acid reactive substances (TBARS) and hydroxy‐2‐nonenal (4‐HNE) levels. RA treatment significantly increased AERP/MMN amplitudes and lowered the TBARS/4‐HNE levels in the OR and ODR groups versus the O and OD groups, respectively. Our findings support the potential benefit of RA in the prevention of auditory distortion related to the estrogen deficiency and d‐galactose administration at least partly by antioxidant actions.

Alterations in spontaneous delta and gamma activity might provide clues to detect changes induced by amyloid-β administration

Alzheimers disease (AD) is the most prevalent form of dementia and has an increasing incidence. The neuropathogenesis of AD is suggested to be a result of the accumulation of amyloid‐β (Aβ) peptides in the brain. To date, Aβ‐induced cognitive and neurophysiologic impairments have not been illuminated sufficiently. Therefore, we aimed to examine how spontaneous brain activities of rats changed by injection of increasing Aβ doses into the brain hemispheres, and whether these changes could be used as a new biomarker for the early diagnosis of the AD. Rats were randomized into following groups: sham (Sham) and seven Aβ‐treated (i.c.v.) groups in increasing concentrations (from Aβ‐1 to Aβ‐7). After recovery, EEG recordings were obtained from implanted electrodes from eight electrode locations, and then, spectral and statistical analyses were performed. A significant decrement in gamma activity was observed in all Aβ groups compared with the sham group. In delta activity, we observed significant changes from Aβ‐4 to Aβ‐7 group compared with sham group. Delta coherence values were decreased from Aβ‐4 to Aβ‐7 and Aβ‐5 to Aβ‐7 groups for frontal and temporal electrode pairs, respectively. A gradual increment was observed in Aβ1‐42 level till Aβ‐4 group. Positive correlation for global delta power and negative correlation for global gamma power between Aβ1‐42 peptide levels were detected. Consequently, it is conceivable to suggest gamma oscillation might be used to detect early stages of AD. Moreover, changes in delta activity provide information about the onset of major pathologic changes in the progress of AD.

Electron microscopic investigations on normal and dexamethasone applied rat placentas

During the growth of foetus in prenatal life glucocorticoids are very important, especially in cell maturation and differentiation events. Today it is known that glucocorticoids lead to intrauterine growth restriction (IUGR) by antiproliferative effects [1].