Mustafa Nazıroğlu

Suleyman Demirel University, Almaty, Almaty Qalasy, Kazakhstan

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Publications (82)168.61 Total impact

  • Mustafa Nazıroğlu, İshak Suat Övey
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    ABSTRACT: Calcium ion accumulation into cytosol of hippocampus and dorsal root ganglion (DRG) are main reasons in etiology of epilepsy. TRPV1 channel is a cation-permeable calcium channel found in the DRG and hippocampus. Although previous studies implicate TRPV1 channels in the generation of epilepsy, suppression of ongoing seizures by TRPV1 antagonists has not yet been investigated. We tested the effects of TRPV1-specific antagonists, capsazepine (CPZ) and 5'-iodoresiniferatoxin (IRTX) on the modulation of calcium accumulation, apoptosis and anticonvulsant properties in hippocampus and DRG of pentylentetrazol (PTZ) and capsaicin (CAP) administrated rats. Forty rats were divided into 5 groups as follows; control, PTZ, CAP+PTZ, IRTX, and IRTX+PTZ. Fura-2 and patch-clamp experiments were performed on neurons dissected from treated animals by CAP and CPZ. PTZ and CAP+PTZ administrations increased intracellular free Ca(2+) concentrations, TRPV1 current densities, apoptosis, caspase 3 and 9 values although the values were reduced by IRTX and CPZ treatments. Latency time was extended by application CPZ and IRTX although CAP produced acceleration of epileptic seizures. Taken together, these results support a role for TRPV1 channels in inhibition of apoptosis, epileptic seizures and calcium accumulation, indicating that TRPV1 inhibition may possibly be a novel target in DRG and hippocampus for prevention of epileptic seizures and peripheral pain. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 03/2015; 293. DOI:10.1016/j.neuroscience.2015.02.041 · 3.33 Impact Factor
  • Bilal Çiğ, Mustafa Nazıroğlu
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    ABSTRACT: TRPV1 is a Ca(2+) permeable channel and gated by noxious heat, oxidative stress and capsaicin (CAP). Some reports have indicated that non-ionized electromagnetic radiation (EMR)-induces heat and oxidative stress effects. We aimed to investigate the effects of distance from sources on calcium signaling, cytosolic ROS production, cell viability, apoptosis, plus caspase-3 and -9 values induced by mobile phones and Wi-Fi in breast cancer cells MCF-7 human breast cancer cell lines were divided into A, B, C and D groups as control, 900, 1800 and 2450MHz groups, respectively. Cells in Group A were used as control and were kept in cell culture conditions without EMR exposure. Groups B, C and D were exposed to the EMR frequencies at different distances (0cm, 1cm, 5cm, 10cm, 20cm and 25cm) for one hour before CAP stimulation. The cytosolic ROS production, Ca(2+) concentrations, apoptosis, caspase-3 and caspase-9 values were higher in groups B, C and D than in A group at 0cm, 1cm and 5cm distances although cell viability (MTT) values were increased by the distances. There was no statistically significant difference in the values between control, 20 and 25cm. Wi-Fi and mobile phone EMR placed within 10cm of the cells induced excessive oxidative responses and apoptosis via TRPV1-induced cytosolic Ca(2+) accumulation in the cancer cells. Using cell phones and Wi-Fi sources which are farther away than 10cm may provide useful protection against oxidative stress, apoptosis and overload of intracellular Ca(2+). This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2015 Elsevier B.V. All rights reserved.
    Biochimica et Biophysica Acta (BBA) - Biomembranes 02/2015; DOI:10.1016/j.bbamem.2015.02.013 · 3.43 Impact Factor
  • S A Köse, M Nazıroğlu
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is a common inflammatory and oxidant disease with an uncertain pathogenesis. N-acetyl cysteine (NAC) decreases oxidative stress, intracellular free calcium ion [Ca(2+)]i, and apoptosis levels in human neutrophil. We aimed to investigate the effects of NAC on apoptosis, oxidative stress, and Ca(2+) entry through transient receptor potential vanilloid 1 (TRPV1) and TRP melastatin 2 (TRPM2) channels in neutrophils from patients with PCOS. Neutrophils isolated from PCOS group were investigated in three settings: (1) after incubation with TRPV1 channel blocker capsazepine or TRPM2 channel blocker 2-aminoethyl diphenylborinate (2-APB), (2) after supplementation with NAC (for 6 weeks), and (3) with combination (capsazepine + 2-APB + NAC) exposure. The neutrophils in TRPM2 and TRPV1 experiments were stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 1 μM) and capsaicin (10 μM) as concentration agonists, respectively. Neutrophil lipid peroxidation and capsaicin-induced increase in [Ca(2+)]i concentrations were reduced by capsazepine and NAC treatments. However, the [Ca(2+)]i concentration did not change by fMLP stimulation. Neutrophil lipid peroxidation, apoptosis, caspase-3, caspase-9, cytosolic reactive oxygen species production, and mitochondrial membrane depolarization values were decreased by NAC treatment although neutrophil glutathione peroxidase and reduced glutathione levels were increased by the NAC treatment. Serum lipid peroxidation, luteinizing hormone, testosterone, insulin, interleukin-1 beta, and homocysteine levels were decreased by NAC treatment although serum vitamin A, beta-carotene, vitamin E, and total antioxidant status were increased by the NAC treatment. In conclusion, NAC reduced oxidative stress, apoptosis, cytokine levels, and Ca(2+) entry through TRPV1 channel, which provide supportive evidence that oxidative stress and TRPV1 channel plays a key role in etiology of PCOS.
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    ABSTRACT: Migraine headaches are considered to be associated with increased mitochondrial energy metabolism. Mitochondrial oxidative stress is also important in migraine headache pathophysiology although riboflavin and selenium (Se) induced a modulator role on mitochondrial oxidative stress in the brain. The current study aimed to determine the effects of Se with/without riboflavin on the microsomal membrane Ca(2+)-ATPase (MMCA), lipid peroxidation, antioxidant, and electroencephalography (EEG) values in glyceryl trinitrate (GTN)-induced brain injury rats. Thirty-two rats were randomly divided into four groups. The first group was used as the control, and the second group was the GTN group. Se and Se plus oral riboflavin were administered to rats constituting the third and fourth groups for 10 days prior to GTN administration. The second, third, and fourth groups received GTN to induce headache. Ten hours after the administration of GTN, the EEG records and brain cortex samples were obtained for all groups. Brain cortex microsomes were obtained from the brain samples. The brain and microsomal lipid peroxidation levels were higher in the GTN group compared to the control group, whereas they were decreased by selenium and selenium + riboflavin treatments. Vitamin A, vitamin C, vitamin E, and reduced glutathione (GSH) concentrations of the brain and MMCA, GSH and glutathione peroxidase values of microsomes were decreased by the GTN administration, although the values and β-carotene concentrations were increased by Se and Se + riboflavin treatments. There was no significant change in EEG records of the four groups. In conclusion, Se with/without riboflavin administration protected against GTN-induced brain oxidative toxicity by inhibiting free radicals and the modulation of MMCA activity and supporting the antioxidant redox system.
    Biological Trace Element Research 12/2014; 164(1). DOI:10.1007/s12011-014-0199-x · 1.61 Impact Factor
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    ABSTRACT: The essential use of riboflavin is the prevention of migraine headaches, although its effect on migraines is considered to be associated with the increased mitochondrial energy metabolism. Oxidative stress is also important in migraine pathophysiology. Vitamin E is a strong antioxidant in nature and its analgesic effect is not completely clear in migraines. The current study aimed to investigate the effects of glyceryl trinitrate (GTN)-sourced exogen nitric oxide (NO), in particular, and also riboflavin and/or vitamin E on involved in the headache model induced via GTN-sourced exogen NO on oxidative stress, total brain calcium levels, and microsomal membrane Ca(2+)-ATPase levels. GTN infusion is a reliable method to provoke migraine-like headaches in experimental animals and humans. GTN resulted in a significant increase in brain cortex and microsomal lipid peroxidation levels although brain calcium, vitamin A, vitamin C, and vitamin E, and brain microsomal-reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and plasma-membrane Ca(2+)-ATPase values decreased through GTN. The lipid peroxidation, GSH, vitamin A, β-carotene, vitamin C, and vitamin E, and calcium concentrations, GSH-Px, and the Ca(2+)-ATPase activities were increased both by riboflavin and vitamin E treatments. Brain calcium and vitamin A concentrations increased through riboflavin only. In conclusion, riboflavin and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system. However, the effects of vitamin E on the values seem more important than in riboflavin.
    Journal of Membrane Biology 11/2014; 248(2). DOI:10.1007/s00232-014-9758-5 · 2.17 Impact Factor
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    ABSTRACT: The present study determined the effects of prenatal and postnatal exposure to Wi-Fi (2.45 GHz)-induced electromagnetic radiation (EMR) on tooth and surrounding tissue development as well as the element levels in growing rats. Twenty-four rats and their offspring were equally divided into two separate groups identified as experiment and control. The experiment group was exposed to 2.45 GHz EMR for 2 h/day during the periods of pregnancy (21 days) and lactation (21 days). The offspring of these dams were also exposed to EMR up to decapitation. The control group was exposed to cage stress for 2 h per day using the same protocol established for the experimental group. On the 7th, 14th, and 21st days after birth, 8 male offspring rats from each of the two groups were decapitated, and the jaws were taken for histological and immunohistochemical examination. Caspase-3 (1/50 dilution) was used in the immunohistochemical examination for apoptotic activity. On the last day of the experiment, the rats' incisors were also collected. In samples that were histologically and immunohistochemically examined, there was an increase in apoptosis and caspase-3 in both the control and the Wi-Fi groups during the development of the teeth. However, no significant difference was observed between the two groups in terms of development and apoptotic activity. Results from the elemental analysis showed that iron and strontium concentrations were increased in the Wi-Fi group, whereas boron, copper, and zinc concentrations were decreased. There were no statistically significant differences in calcium, cadmium, potassium, magnesium, sodium, or phosphorus values between the groups. Histological and immunohistochemical examinations between the experimental and control groups showed that exposure to 2.45 GHz EMR for 2 h per day does not interfere with the development of teeth and surrounding tissues. However, there were alterations in the elemental composition of the teeth, especially affecting such oxidative stress-related elements as copper, zinc, and iron, suggesting that short-term exposure to Wi-Fi-induced EMR may cause an imbalance in the oxidative stress condition in the teeth of growing rats.
    Biological Trace Element Research 11/2014; 163(1-2). DOI:10.1007/s12011-014-0175-5 · 1.61 Impact Factor
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    ABSTRACT: Electromagnetic radiation (EMR) and epilepsy are reported to mediate the regulation of apoptosis and oxidative stress through Ca(2+) influx. Results of recent reports indicated that EMR can increase temperature and oxidative stress of body cells, and TRPV1 channel is activated by noxious heat, oxidative stress, and capsaicin (CAP). We investigated the effects of mobile phone (900 MHz) EMR exposure on Ca(2+) influx, apoptosis, oxidative stress, and TRPV1 channel activations in the hippocampus of pentylenetetrazol (PTZ)-induced epileptic rats. Freshly isolated hippocampal neurons of twenty-one rats were used in study within three groups namely control, PTZ, and PTZ + EMR. The neurons in the three groups were stimulated by CAP. Epilepsy was induced by PTZ administration. The neurons in PTZ + EMR group were exposed to the 900 MHz EMR for 1 h. The apoptosis, mitochondrial membrane depolarization, intracellular reactive oxygen species (ROS), and caspase-3 and caspase-9 values were higher in PTZ and PTZ + EMR groups than in control. However, EMR did not add additional increase effects on the values in the hippocampal neurons. Intracellular-free Ca(2+) concentrations in fura-2 analyses were also higher in PTZ + CAP group than in control although their concentrations were decreased by TRPV1 channel blocker, capsazepine. However, there were no statistical changes on the Ca(2+) concentrations between epilepsy and EMR groups. In conclusion, apoptosis, mitochondrial, ROS, and Ca(2+) influx via TRPV1 channel were increased in the hippocampal neurons by epilepsy induction although the mobile phone did not change the values. The results indicated that TRPV1 channels in hippocampus may possibly be a novel target for effective target of epilepsy.
    Journal of Membrane Biology 11/2014; DOI:10.1007/s00232-014-9744-y · 2.17 Impact Factor
  • Vehbi Yürüker, Mustafa Nazıroğlu, Nilgün Senol
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    ABSTRACT: Melatonin, which is a very effective reactive oxygen species (ROS) scavenger, acts through a direct reaction with free radicals. Ca(2+) entry induced by traumatic brain injury (TBI) has deleterious effects on human hippocampal function. TRPM2 is a Ca(2+) permeable non-selective channel in hippocampal neurons, and its activation of during oxidative stress has been linked to cell death. Despite the importance of oxidative stress in TBI, its role in apoptosis and Ca(2+) entry in TBI is poorly understood. Therefore, we tested the effects of melatonin on apoptosis, oxidative stress, and Ca(2+) entry through the TRPM2 channel in the hippocampal neurons of TBI-induced rats. Thirty-two rats were divided into the following four groups: control, melatonin, TBI, and TBI + melatonin groups. Melatonin (5 mg/kg body weight) was intraperitoneally given to animals in the melatonin group and the TBI + melatonin group after 1 h of brain trauma. Hippocampal neurons were freshly isolated from the four groups, incubated with a nonspecific TRPM2 blocker (2-aminoethyl diphenylborinate, 2-APB), and then stimulated with cumene hydroperoxide. Apoptosis, caspase-3, caspase-9, intracellular ROS production, mitochondrial membrane depolarization and intracellular free Ca(2+) ([Ca(2+)]i) values were high in the TBI group, and low in the TBI + melatonin group. The [Ca(2+)]i concentration was decreased in the four groups by 2-APB. In our TBI experimental model, TRPM2 channels were involved in Ca(2+) entry-induced neuronal death, and the negative modulation of the activity of this channel by melatonin pretreatment may account for the neuroprotective activity of TRPM2 channels against oxidative stress, apoptosis, and Ca(2+) entry.
    Metabolic Brain Disease 10/2014; 30(1). DOI:10.1007/s11011-014-9623-3 · 2.40 Impact Factor
  • Ishak Suat Ovey, Mustafa Nazıroğlu
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    ABSTRACT: Oxidative stress and apoptosis were induced in neuronal cultures by inhibition of glutathione (GSH) biosynthesis with D,L-buthionine-S,R-sulfoximine (BSO). TRPM2 and TRPV1 cation channels are gated by oxidative stress. The oxidant effects of homocysteine (Hcy) may induce activation of TRPV1 and TRPM2 channels in aged mice as a model of Alzheimer's disease (AD). We tested the effects of Hcy, BSO and GSH on oxidative stress, apoptosis and Ca(2+) and influx via TRPM2 and TRPV1 channels in hippocampus of mice. Native mice hippocampus neurons were divided into 5 groups as follows; control, Hcy, BSO, Hcy+BSO and Hcy+BSO+GSH groups. The neurons in TRPM2 and TRPV1 experiments were stimulated by hydrogen peroxide and capsaicin, respectively. BSO and Hcy incubations increased intracellular free Ca(2+) concentrations, reactive oxygen species, apoptosis, mitochondrial depolarization, and levels of caspase 3 and 9. All of these increases were reduced by GSH treatments. Treatment with 2-aminoethyldiphenyl borate (2-APB) and N-(p-amylcinnamoyl)anthranilic acid (ACA) as potent inhibitors of TRPM2, capsazepine as a potent inhibitor of TRPV1, verapamil+diltiazem (V+D) as inhibitors of the voltage-gated Ca(2+) channels (VGCC) and MK-801 as a NMDA channel antagonist indicated that GSH depletion and Hcy elevation activated Ca(2+) entry into the neurons through TRPM2, TRPV1, VGCC and NMDA channels., Inhibitor roles of 2-APB and capsazepine on the Ca(2+) entry higher than in V+D and MK-801 antagonists. In conclusion, these findings support the idea that GSH depletion and Hcy elevation can have damaging effects on hippocampal neurons by perturbing calcium homeostasis, mainly through TRPM2 and TRPV1 channels. GSH treatment can partially reverse these effects.
    Neuroscience 10/2014; DOI:10.1016/j.neuroscience.2014.09.078 · 3.33 Impact Factor
  • Mehmet Cemal Kahya, Mustafa Nazıroğlu, Bilal Ciğ
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    ABSTRACT: Exposure to mobile phone-induced electromagnetic radiation (EMR) may affect biological systems by increasing free oxygen radicals, apoptosis, and mitochondrial depolarization levels although selenium may modulate the values in cancer. The present study was designed to investigate the effects of 900 MHz radiation on the antioxidant redox system, apoptosis, and mitochondrial depolarization levels in MDA-MB-231 breast cancer cell line. Cultures of the cancer cells were divided into four main groups as controls, selenium, EMR, and EMR + selenium. In EMR groups, the cells were exposed to 900 MHz EMR for 1 h (SAR value of the EMR was 0.36 ± 0.02 W/kg). In selenium groups, the cells were also incubated with sodium selenite for 1 h before EMR exposure. Then, the following values were analyzed: (a) cell viability, (b) intracellular ROS production, (c) mitochondrial membrane depolarization, (d) cell apoptosis, and (e) caspase-3 and caspase-9 values. Selenium suppressed EMR-induced oxidative cell damage and cell viability (MTT) through a reduction of oxidative stress and restoring mitochondrial membrane potential. Additionally, selenium indicated anti-apoptotic effects, as demonstrated by plate reader analyses of apoptosis levels and caspase-3 and caspase-9 values. In conclusion, 900 MHz EMR appears to induce apoptosis effects through oxidative stress and mitochondrial depolarization although incubation of selenium seems to counteract the effects on apoptosis and oxidative stress.
    Biological Trace Element Research 06/2014; 160(2). DOI:10.1007/s12011-014-0032-6 · 1.61 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the potentially beneficial effects of apple cider vinegar (ACV) supplementation on serum triglycerides, total cholesterol, liver and kidney membrane lipid peroxidation, and antioxidant levels in ovariectomized (OVX) mice fed high cholesterol. Four groups of ten female mice were treated as follows: Group I received no treatment and was used as control. Group II was OVX mice. Group III received ACV intragastrically (0.6 % of feed), and group IV was OVX and was treated with ACV as described for group III. The treatment was continued for 28 days, during which the mice were fed a high-cholesterol diet. The lipid peroxidation levels in erythrocyte, liver and kidney, triglycerides, total, and VLDL cholesterol levels in serum were higher in the OVX group than in groups III and IV. The levels of vitamin E in liver, the kidney and erythrocyte glutathione peroxidase (GSH-Px), and erythrocyte-reduced glutathione (GSH) were decreased in group II. The GSH-Px, vitamin C, E, and β-carotene, and the erythrocyte GSH and GSH-Px values were higher in kidney of groups III and IV, but in liver the vitamin E and β-carotene concentrations were decreased. In conclusion, ACV induced a protective effect against erythrocyte, kidney, and liver oxidative injury, and lowered the serum lipid levels in mice fed high cholesterol, suggesting that it possesses oxidative stress scavenging effects, inhibits lipid peroxidation, and increases the levels of antioxidant enzymes and vitamin.
    Journal of Membrane Biology 06/2014; DOI:10.1007/s00232-014-9685-5 · 2.17 Impact Factor
  • Nilgün Senol, Mustafa Nazıroğlu
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    ABSTRACT: Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We investigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vitamin E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain injury-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.
    Neural Regeneration Research 06/2014; 9(11):1112-6. DOI:10.4103/1673-5374.135312 · 0.23 Impact Factor
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    ABSTRACT: Neurodegeneration associated with acute central nervous system injuries and diseases such as spinal cord injury and traumatic brain injury (TBI) are reported to be mediated by the regulation of apoptosis and oxidative stress through Ca(2+) influx. The thiol redox system antioxidants, such as N-acetylcysteine (NAC) and selenium (Se), display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties. However, there are no reports on hippocampal apoptosis, cytosolic reactive oxygen species (ROS), or Ca(2+) values in rats with an induced TBI. Therefore, we tested the effects of Se and NAC administration on apoptosis, oxidative stress, and Ca(2+) influx through TRPV1 channel activations in the hippocampus of TBI-induced rats. The 32 rats were divided into four groups: control, TBI, TBI + NAC, and TBI + Se groups. Intraperitoneal administrations of NAC and Se were performed at 1, 24, 48, and 72 h after TBI induction. After 3 days, the hippocampal neurons were freshly isolated from the rats. In cytosolic-free Ca(2+) analyses, the neurons were stimulated with the TRPV1 channel agonist capsaicin, a pungent compound found in hot chili peppers. Cytosolic-free Ca(2+), apoptosis, cytosolic ROS levels, and caspase-3 and -9 activities were higher in the TBI group than control. The values in the hippocampus were decreased by Se and NAC administrations. In conclusion, we observed that NAC and Se have protective effects on oxidative stress, apoptosis, and Ca(2+) entry via TRPV1 channel activation in the hippocampus of this TBI model, but the effect of NAC appears to be much greater than that of Se. They are both interesting candidates for studying the amelioration of TBIs.
    Cellular and Molecular Neurobiology 05/2014; DOI:10.1007/s10571-014-0069-2 · 2.20 Impact Factor
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    ABSTRACT: Abstract Background: Despite the importance of oxidative stress and apoptosis through mitochondrial depolarization in neurodegenerative diseases, their roles in etiology of glaucoma are poorly understood. We aimed to investigate whether oxidative stress and apoptosis formation are altered in rat pheochromocytoma-derived cell line-12 (PC12) neuronal cell cultures exposed to elevated different hydrostatic pressures as a cell culture model of glaucoma. Materials: Cultured PC12 cells were subjected to 0, 15 and 70 mmHg hydrostatic pressure for 1 and 24 h. Then, the following values were analyzed: (a) cell viability; (b) lipid peroxidation and intracellular reactive oxygen species production; (c) mitochondrial membrane depolarization; (d) cell apoptosis; (e) caspase-3 and caspase-9 activities; (f) reduced glutathione (GSH) and glutathione peroxidase (GSH-Px). Results: The hydrostatic pressures (15 and 70 mmHg) increased oxidative cell damage through a decrease of GSH and GSH-Px values, and increasing mitochondrial membrane potential. Additionally, 70 mmHg hydrostatic pressure for 24 h indicated highest apoptotic effects, as demonstrated by plate reader analyses of apoptosis, caspase-3 and -9 values. Conclusion: The present data indicated oxidative stress, apoptosis and mitochondrial changes in PC12 cell line during different hydrostatic pressure as a cell culture model of glaucoma. This findings support the view that mitochondrial oxidative injury contributes early to glaucomatous optic neuropathy.
    Journal of Receptor and Signal Transduction Research 05/2014; DOI:10.3109/10799893.2014.910812 · 1.61 Impact Factor
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    Vahid Ghazizadeh, Mustafa Nazıroğlu
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    ABSTRACT: Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.
    Metabolic Brain Disease 05/2014; DOI:10.1007/s11011-014-9549-9 · 2.40 Impact Factor
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    ABSTRACT: Calcium ion (Ca(2+)) is one of the universal second messengers, which acts in a wide range of cellular processes. Results of recent studies indicated that ROS generated by depression leads to loss of endoplasmic reticulum-Ca(2+) homeostasis, oxidative stress, and apoptosis. Agomelatine and duloxetine are novel antidepressant and antioxidant drugs and may reduce oxidative stress, apoptosis, and Ca(2+) entry through TRPM2 and voltage-gated calcium channels. We tested the effects of agomelatine, duloxetine, and their combination on oxidative stress, Ca(2+) influx, mitochondrial depolarization, apoptosis, and caspase values in the PC-12 neuronal cells. PC-12 neuronal cells were exposed in cell culture and exposed to appropriate non-toxic concentrations and incubation times for agomelatine were determined in the neurons by assessing cell viability. Then PC-12 cells were incubated with agomelatine and duloxetine for 24 h. Treatment of cultured PC-12 cells with agomelatine, duloxetine, and their combination results in a protection on apoptosis, caspase-3, caspase-9, mitochondrial membrane depolarization, cytosolic ROS production, glutathione peroxidase, reduced glutathione, and lipid peroxidation, values. Ca(2+) entry through non-specific TRPM2 channel blocker (2-APB) and voltage-gated Ca(2+) channel blockers (verapamil and diltiazem) was modulated by agomelatine and duloxetine. However, effects of duloxetine on the Ca(2+) entry through TRPM2 channels were higher than in agomelatine. Results of current study suggest that the agomelatine and duloxetine are useful against apoptotic cell death and oxidative stress in PC-12 cells, which seem to be dependent on mitochondrial damage and increased levels of intracellular Ca(2+) through activation of TRPM2 and voltage-gated Ca(2+) channels.
    Journal of Membrane Biology 03/2014; 247(5). DOI:10.1007/s00232-014-9652-1 · 2.17 Impact Factor
  • Seyit Ali Köse, Mustafa Nazıroğlu
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is a common inflammatory disease with an uncertain pathogenesis, although one consistent finding is increased neutrophil activity. It has been recently reported that the essential antioxidant element selenium has protective effects on oxidative stress and cytosolic Ca(2+) concentrations in human neutrophil. We aimed to investigate the effects of selenium on oxidative stress and Ca(2+) levels through TRPV1 channels in neutrophils from patients with PCOS. Blood samples were obtained for neutrophil isolation from ten female patients with PCOS and ten healthy female subjects. Neutrophils isolated from PCOS group were investigated in four settings: (1) PCOS, (2) after incubation with TRPV1 channel blocker capsazepine (CPZ), (3) after incubation with selenium (sodium selenite), and (4) with combination (CPZ + selenium) exposure. Intracellular free Ca(2+) concentrations were higher in the patients than those in the controls, although their levels were reduced after CPZ and selenium incubations. The cytosolic Ca(2+) concentrations in neutrophils obtained from PCOS group were further decreased after incubation with CPZ + selenium, as compared with those exposed to neither agent. Lipid peroxidation levels were higher in the PCOS group than those in the control although neutrophil glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) values were decreased. The lipid peroxidation level was lower in the CPZ and selenium groups than that in the PCOS group although GSH and GSH-Px values were higher in the treatment with selenium and CPZ. In conclusion, we observed the importance of Ca(2+) influx into the neutrophils through TRPV1 channels in the pathogenesis of the patients with PCOS. The selenium appeared to provide a protective effect against oxidative stress and Ca(2+) entry through modulation of neutrophil TRPV1 calcium channels.
    Biological trace element research 03/2014; 158(2). DOI:10.1007/s12011-014-9929-3 · 1.61 Impact Factor
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    ABSTRACT: Abstract Objectives: The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. Methods: Thirty-two rats and their offspring were equally divided into 3 different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/day during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. Results: Brain and liver glutathione peroxidase (GSH-Px) activities, as well as liver vitamin A and β-carotene concentrations decreased in the EMR groups, although brain iron, vitamin A, and β-carotene concentrations increased in the EMR groups. In the 6th week, selenium concentrations in the brain decreased in the EMR groups. There were no statistically significant differences in glutathione, vitamin E, chromium, copper, magnesium, manganese, and zinc concentrations between the 3 groups. Conclusion: EMR-induced oxidative stress in the brain and liver was reduced during the development of offspring. Mobile phone-induced EMR could be considered as a cause of oxidative brain and liver injury in growing rats.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 03/2014; DOI:10.3109/14767058.2014.898056 · 1.21 Impact Factor
  • Nilgün Senol, Mustafa Nazıroğlu, Vehbi Yürüker
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    ABSTRACT: It has been suggested that oxidative stress plays an important role in the pathophysiology of traumatic brain injury (TBI). N-acetylcysteine (NAC) and selenium (Se) display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties although there is no report on oxidative stress, antioxidant vitamin, interleukin-1 beta (IL)-1β and IL-4 levels in brain and blood of TBI-induced rats. We investigated effects of NAC and Se administration on physical injury-induced brain toxicity in rats. Thirty-six male Sprague-Dawley rats were equally divided into four groups. First and second groups were used as control and TBI groups, respectively. NAC and Se were administrated to rats constituting third and forth groups at 1, 24, 48 and 72 h after TBI induction, respectively. At the end of 72 h, plasma, erythrocytes and brain cortex samples were taken. TBI resulted in significant increase in brain cortex, erythrocytes and plasma lipid peroxidation, total oxidant status (TOS) in brain cortex, and plasma IL-1β values although brain cortex vitamin A, β-carotene, vitamin C, vitamin E, reduced glutathione (GSH) and total antioxidant status (TAS) values, and plasma vitamin E concentrations, plasma IL-4 level and brain cortex and erythrocyte glutathione peroxidase (GSH-Px) activities decreased by TBI. The lipid peroxidation and IL-1β values were decreased by NAC and Se treatments. Plasma IL-4, brain cortex GSH, TAS, vitamin C and vitamin E values were increased by NAC and Se treatments although the brain cortex vitamin A and erythrocyte GSH-Px values were increased through NAC only. In conclusion, NAC and Se caused protective effects on the TBI-induced oxidative brain injury and interleukin production by inhibiting free radical production, regulation of cytokine-dependent processes and supporting antioxidant redox system.
    Neurochemical Research 02/2014; 39(4). DOI:10.1007/s11064-014-1255-9 · 2.55 Impact Factor