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Öğe Anakinra, an interleukin-1 receptor antagonist, increases the morphine analgesic effect and decreases morphine tolerance development by modulating oxidative stress and endoplasmic reticulum stress in rats(Tubitak Scientific & Technological Research Council Turkey, 2020) Avci, Onur; Taskiran, Ahmet SevkiBackground/aim: Recent studies have shown that inflammation plays a role in morphine analgesia and tolerance development. Anakinra is a competitive inhibitor of IL-1 receptors and an antiinflammatory protein regulating IL-1 beta's biological activity by avoiding signal transduction. In this study, we aimed to examine the effects of anakinra on morphine analgesia and tolerance. Materials and methods: In this study, 36 Wistar Albino (230-250 g) male rats were used. Animals were divided into 6 groups: saline (S), 100 mg/kg anakinra (A), 5mg/kg morphine (M), M-FA, morphine tolerance (MT), and MT+A. The resulting analgesic effect was measured with hot plate and tail-flick analgesia tests. After the analgesia tests, the dorsal root ganglions (DRG) tissues were removed. Oxidative stress parameters [total antioxidant status (TAS), total oxidant status (FOS)] , endoplasmic reticulum (ER) stress, and apoptosis proteins [E74-like factor 2 (elF-2 alpha), activating transcription factor 4 (ATF-4), C/EBP homologous protein (CHOP), caspase-3, and bcl-2-associated X protein (bax)1 were measured in DRG tissues. Results: Anakinra showed an antinociceptive effect when given alone (1) < 0.001). In addition, anakinra increased the analgesic effect of morphine (P < 0.05 to P < 0.001), and also decreased the tolerance to morphine at a significant level (P < 0.05 to P < 0.001). Moreover, it decreased oxidative stress and ER-stress when given as a single-dose morphine and tolerance induction (P < 0.01 to P < 0.001). Furthermore, anakinra decreased apoptosis proteins after tolerance development (P < 0.001). Conclusion: Anakinra has antinociceptive properties, and it increases the analgesic effect of morphine and also prevents tolerance development. These effects probably occur by the modulation of oxidative stress and ER-stress pathways.Öğe Blockade of orexin receptor type-1 by SB-334867 and activation of orexin receptor type-2 attenuate morphine tolerance in rats(Akademiai Kiado Zrt, 2022) Ozdemir, Ercan; Baser, Tayfun; Taskiran, Ahmet SevkiPurpose: The interaction of orexinergic neurons with the opioidergic system and their effects on morphine analgesia and tolerance have not been fully elucidated. The purpose of the study was to evaluate the effects of the orexin-1 and orexin-2 receptor (OX1R and OX2R) agonist and antagonist on morphine analgesia and tolerance in rats. Material and methods: A total of 90 Wistar albino male rats weighing 180-220 g were used in the experiments. To induce morphine tolerance, rats were injected with a single dose of morphine (50 mg kg -1, s.c.) for 3 days. Morphine tolerance was assessed on day 4 in randomly selected rats by analgesia tests. In order to evaluate morphine tolerance situation, orexin-A, SB-334867, orexin-B and TCS OX2 29 were administered together with morphine for 3 days. The analgesic effects of orexin-A (10 jig kg -1), OXR1 antagonist SB-334867 (10 mg kg -1), OXR2 agonist orexin-B (15 jig kg -1), OXR2 antagonist TCS OX2 29 (0.5 mg kg -1) and morphine (5 mg kg -1) were measured at 15 or 30-min intervals by tail -flick and hot-plate antinociceptive tests. Results: The results suggested that the combination of orexin-1 receptor antagonist SB-334867 and orexin-B with morphine significantly increased the analgesic effect compared to morphine-tolerant rats. In addition, administration of orexin-A and-B alone showed significant analgesic effects compared to the saline group. However, co-administration of orexin-A and-B with morphine did not increase the analgesic efficacy of morphine. Conclusions: The results of this study demonstrated that co-administration of SB-334867 and orexin-B with morphine attenuated morphine tolerance. Further studies are needed to elucidate the details of the interaction between orexin receptors and the opioidergic system.Öğe Bromelain Protects Against PTZ-Induced Glial Damage and Inflammation: An In Vitro and In Silico Study(Humana Press Inc, 2025) Joha, Ziad; Basgoz, Neslihan; Ozgur, Aykut; Taskiran, Ahmet SevkiThis study aimed to investigate how bromelain protects glial cells from pentylenetetrazole (PTZ)-induced damage, focusing on its anti-inflammatory effects. C6 glioma cells were treated with PTZ, bromelain, or a combination of PTZ and bromelain. The interactions of bromelain with iNOS (Inducible Nitric Oxide Synthase) and COX2 (Cyclooxygenase-2) were investigated using molecular docking calculations. Cell viability was measured using the XTT (Methoxynitrosulfophenyl-Tetrazolium Carboxanilide) assay. iNOS, NO (Nitric Oxide), and COX2 levels were assessed using ELISA and immunofluorescence staining. Bromelain at 50 and 100 mu g/mL significantly increased cell viability (p < 0.001). On the other hand, bromelain at 50 g/mL reduced inflammation, as indicated by lower levels of NO, iNOS, and COX2 (p < 0.001). In-silico predictions suggest that bromelain can effectively target iNOS and COX2, key inflammatory proteins. These findings indicate that bromelain protects glial cells by exerting anti-inflammatory effects. However, further research is needed to understand the underlying mechanisms fully.Öğe Comparison of Analgesic Effects Induced by Different Strengths of Extremely Low-Frequency Electromagnetic Fields(AVES PRESS LTD, 2018) Demirkazik, Ayse; Ozdemir, Ercan; Turkay, Yavuz; Pelit, Aykut; Kilinc, Olca; Taskiran, Ahmet Sevki; Arslan, GokhanObjective: Our aim was to compare the results of the most commonly used analgesic measurement techniques and to determine the time and intensity at which the analgesic effects of the magnetic field (MF) are most effective. Methods: This study compared the analgesic effect of MF strengths (1, 5, and 10 mT) in 30 adults, male Wistar albino rats weighing 200-250 g. The analgesic effects were measured using tail-flick (TF) and hot-plate (HP) tests. To determine the optimum MF strength, rats were assigned into four groups: sham group and exposed to 1, 5, and 10 mT MF groups. Rats were placed in a solenoid, and MF of 50 Hz for 165 min was administered daily for 15 days. All four groups were kept in the solenoid for 165 min/15 days and exposed to MF. However, the analgesic effect was measured only on day 0, 4, 7, 11, and 15 using TF and HP tests. The latencies of analgesia were converted to a percentage of maximal antinociceptive effects (% MPE). Results: When the maximum analgesic effect of the 5 mT MF was determined on the seventh day, the% MPEs were 5.37 +/- 0.51, 13.66 +/- 1.27, 25.89 +/- 3.00, and 25.37 +/- 2.41 in the sham, 1 mT, 5 mT, and 10 mT groups, respectively. The optimum effect was observed with 5 mT MF on the seventh day and with 90 min in the solenoid. Conclusion: We didn't find any differences between the analgesic responses to the TF and HP tests.Öğe The Effect of beta-Carotene on Spike Wave Discharges in Genetic Absence Epileptic WAG/Rij Rats(WILEY-BLACKWELL, 2016) Derelioglu, Gamze; Olgen, Zuleyha; Taskiran, Ahmet Sevki; Ozdemir, Ercan; Gulturk, Sefa; Arslan, Gokhan…Öğe Effect of captopril, an angiotensin-converting enzyme inhibitor, on morphine analgesia and tolerance in rats, and elucidating the inflammation and endoplasmic reticulum stress pathway in this effect(Elsevier Ireland Ltd, 2021) Taskiran, Ahmet Sevki; Avci, OnurThe purpose of current study was to examine the possible involvement of captopril, an angiotensin-converting enzyme inhibitor, on nociception, morphine analgesia and morphine tolerance development involving inflammation and ER-stress pathways in rats. In this study, thirty-six male Wistar rats were used. Animals were divided into six groups: Saline, 50 mg/kg captopril, 5 mg/kg morphine, morphine + captopril, morphine tolerance and morphine tolerance + captopril. The resulting analgesic effect was measured with hot plate and tail flick analgesia tests. The dorsal root ganglions (DRG) tissues were collected for inflammation parameters, endoplasmic reticulum (ER) stress and apoptosis proteins by using ELISA. Captopril showed anti-nociceptive effect when given alone (p < 0.05 to p < 0.01). In addition, captopril increased the analgesic effect of morphine (p < 0.05 to p < 0.001) and also decreased the tolerance to morphine at a significant level (p < 0.05 to p < 0.001). However, it decreased inflammation and ER-stress when applied with single-dose morphine and tolerance induction (p < 0.001). Moreover, captopril decreased apoptosis proteins after tolerance development (p < 0.001). In conclusion, captopril has antinociceptive properties, increasing analgesic effect of morphine, and preventing tolerance development. These effects may occur by suppressing inflammation and ER-stress pathways.Öğe The Effect of Ghrelin Receptor on Morphine Analgesia and Tolerance in Rats(KARGER, 2018) Baser, Tayfun; Ozdemir, Ercan; Taskiran, Ahmet Sevki; Arslan, Gokhan…Öğe Effect of ovarian stimulation on the expression of piRNA pathway proteins(Public Library Science, 2020) Sari, Ismail; Gumus, Erkan; Taskiran, Ahmet Sevki; Sokmensuer, Lale KarakocPIWI-interacting RNAs (piRNAs) play an important role in gametogenesis, fertility and embryonic development. The current study investigated the effect of different doses of pregnant mare serum gonadotrophin/human chorionic gonadotrophin (PMSG/hCG) and repeated ovarian stimulation (OS) on the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9, qnd Mitopld genes, which have crucial roles in the biogenesis and function of piRNAs. Here, we found that after treatment with 7.5 I.U. PMSG/hCG and two repeated rounds of OS, both the mRNA and protein levels of Tdrd9, Tdrd1 and Mael showed the greatest decrease in the ovarian tissue, but the plasma E-2 levels showed the strongest increases (p< 0.05). However, we found that the Mitopld, Miwi and Mili gene levels were decreased significantly after treatment with 12.5 I.U. PMSG/hCG. Our results suggested that exogenous gonadotropin administration leads to a significant decrease in the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9 and Mitopld genes, which are critically important in the piRNA pathway, and the changes in the expression levels of Tdrd9, Tdrd1 and Mael may be associated with plasma E-2 levels. New comprehensive studies are needed to reduce the potential effects of OS on the piRNA pathway, which silences transposable elements and maintains genome integrity, and to contribute to the safety of OS.Öğe The Effect of Post-Learning REM Sleep Deprivation on Hipocampal REST Tomosyn Expression in Mice(WILEY, 2017) Karabulut, Sebahattin; Bayramov, Kezban Korkmaz; Ozdemir, Fadime; Topaloglu, Tugba; Ergen, Ergul; Taskiran, Ahmet Sevki; Golgeli, Asuman…Öğe Effect of The Cyclooxygenase-2 Inhibitor Tenoxicam on Pentylenetetrazole-Induced Epileptic Seizures in Rats(WILEY, 2017) Toptas, Hacer Aybike; Guney, Ozge; Kutlu, Rukiye; Gumus, Ekan; Gunes, Handan; Taskiran, Ahmet Sevki; Arslan, Gokhan…Öğe Effects of 5-HT1 and 5-HT2 Receptor Agonists on Electromagnetic Field-Induced Analgesia in Rats(WILEY, 2019) Ozdemir, Ercan; Demirkazik, Ayse; Taskiran, Ahmet Sevki; Arslan, GokhanMuch evidence demonstrates the antinociceptive effect of magnetic fields (MFs). However, the analgesic action mechanism of the electromagnetic field (EMF) is not exactly understood. The aim of the present study was to investigate the effects of 5-HT1 and 5-HT2 receptor agonists (serotonin HCl and 2,5-dimethoxy-4-iodoamphetamine [DOI] hydrochloride) on EMF-induced analgesia. In total, 66 adult male Wistar albino rats with an average body mass of 225 +/- 13 g were used in this study. The animals were subjected to repeated exposures of alternating 50 Hz and 5 mT EMF for 2 h a day for 15 days. Prior to analgesia tests, serotonin HCl (5-HT1 agonist) 4 mg/kg, WAY 100635 (5-HT1 antagonist) 0.04 mg/kg, DOI hydrochloride (5-HT2 receptor agonist) 4 mg/kg, and SB 204741 (5-HT2 antagonist) 0.5 mg/kg doses were injected into rats. For statistical analysis of the data, analysis of variance was used and multiple comparisons were determined by Tukey's test. Administration of serotonin HCl MF (5 mT)-exposed rats produced a significant increase in percent maximal possible effect (% MPE) as compared with EMF group (P < 0.05). On the contrary, injection of WAY 100635 to MF-exposed rats produced a significant decrease in analgesic activity (P < 0.05). Similarly, the administration of DOI hydrochloride significantly increased % MPE values as compared with the EMF group while SB 204741 reduced it (P < 0.05). In conclusion, our results suggested that serotonin 5-HT1 and 5-HT2 receptors play an important role in EMF-induced analgesia; however, further research studies are necessary to understand the mechanism. Bioelectromagnetics. 2019;40:319-330. (c) 2019 Bioelectromagnetics Society.Öğe Effects of Dopamine D1 and D2 Receptors on Analgesia Created By a Very Low Frequency Electromagnetic Field in Rats(WILEY, 2017) Arslan, Gokhan; Demirkazik, Ayse; Ozdemir, Ercan; Taskiran, Ahmet Sevki; Kilinc, Olca…Öğe Effects of Nitric Oxide Synthase (NOS) Inhibitors on Analgesia Induced by Extremely Low Frequency Magnetic Field in Rats(WILEY, 2017) Ozdemir, Ercan; Demirkazik, Ayse; Taskiran, Ahmet Sevki; Kilinc, Olca; Arslan, Gokhan…Öğe Effects of Oxytocin Receptor Antagonist Atosiban on Analgesia and Morphine Analgesia in Rats(WILEY, 2017) Taskiran, Ahmet Sevki; Erdem, Berat; Gunes, Handan; Ozdemir, Ercan…Öğe Effects of post-learning REM sleep deprivation on hippocampal plasticity-related genes and microRNA in mice(ELSEVIER SCIENCE BV, 2019) Karabulut, Sebahattin; Bayramov, Keziban Korkmaz; Bayramov, Ruslan; Ozdemir, Fadime; Topaloglu, Tugba; Ergen, Ergul; Yazgan, Kamile; Taskiran, Ahmet Sevki; Golgeli, AsumanSleep is essential for memory consolidation that stabilizes a memory trace. Memory consolidation includes waves of new gene expression and protein synthesis. Recently, microRNAs (miRNAs) have emerged as critical regulators of memory processes. Previous studies demonstrated that rapid eye movement (REM) sleep deprivation (REM SD) during specific time windows after training in the Morris water maze (MWM) task impairs memory consolidation. Here, we showed that the post-learning REM sleep, extending from 3 to 6 h after last training, is critical for spatial learning in the MWM task. Further, we found that the REM SD after training significantly changes the hippocampal expression of brain-derived neurotrophic factor (BDNF) mRNA; however, it causes minimal difference in the hippocampal expressions of calcium-calmodulin-dependent protein kinase II (CAMKII) and cAMP response-element-binding (CREB). In addition, it considerably affected the hippocampal expressions of miR-132, miR-182, and miR-124. In conclusion, after the MWM task, the post-learning REM sleep during specific time windows can modulate spatial memory consolidation, and its deprivation can impact the hippocampal transcriptional processes including memory-related miRNAs and mRNAs.Öğe Effects of the Phosphodiesterase Type 5 Inhibitor Tadalafil on Morphine Analgesia and Tolerance in Rats(WILEY, 2017) Taskiran, Ahmet Sevki; Ozdemir, Ercan; Arslan, Gokhan…Öğe The Effects of Very Low Frequency Electromagnetic Fields on Morphine Analgesia and Tolerance in Rats(WILEY-BLACKWELL, 2016) Ozdemir, Ercan; Cancalar, Ayse Demirkazik; Taskiran, Ahmet Sevki; Kilinc, Olca; Arslan, Gokhan…Öğe Enoxaparin Protects C6 Glioma Cells from Glutamate-Induced Cytotoxicity by Reducing Oxidative Stress and Apoptosis(Springer, 2025) Yulak, Fatih; Joha, Ziad; Ozturk, Aysegul; Inan, Zeynep Deniz Sahin; Taskiran, Ahmet SevkiRecent studies suggest enoxaparin may protect the central nervous system (CNS) from damage. However, its specific effects on glial cells and the underlying mechanisms involving cell death and oxidative stress require further investigation. Therefore, this research investigated enoxaparin's potential to safeguard C6 glioma cells against glutamate-induced cytotoxicity, specifically focusing on its influence on oxidative stress and apoptotic mechanisms. To investigate the neuroprotective effects of enoxaparin against glutamate-induced cytotoxicity in C6 cells, four groups were established: a control group, a group exposed to 10 mM glutamate, a group treated with enoxaparin at concentrations ranging from 25 to 200 mu M, and a group receiving both 10 mM glutamate and enoxaparin at concentrations ranging from 25 to 200 mu M. Cell viability was measured using an XTT assay. To evaluate the effects of enoxaparin on oxidative stress, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using ELISA, along with total antioxidant status (TAS) and total oxidant status (TOS). Apoptosis was evaluated using flow cytometry, and caspase-3 activity, a key marker of apoptosis, was assessed using caspase-3 immunofluorescence staining. Enoxaparin at 50, 100, and 200 mu M markedly increased cell viability in the enoxaparin + glutamate group. Enoxaparin treatment in the enoxaparin + glutamate group also significantly elevated levels of SOD and TAS, while concurrently decreasing MDA and TOS levels. These changes indicate a reduction in oxidative stress. Enoxaparin treatment further resulted in a significant decline in cleaved caspase-3 levels, a marker of apoptosis. Enoxaparin pre-treatment reduced cell death according to flow cytometry analysis. This study suggests enoxaparin's potential to shield C6 glioma cells from glutamate-induced cell death by mitigating both oxidative stress and apoptotic pathways. More research is needed to confirm this effect.Öğe Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis(Korean Pain Soc, 2024) Dirik, Hasan; Taskiran, Ahmet Sevki; Joha, ZiadBackground: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.Öğe Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats(Canadian Science Publishing, 2021) Baser, Tayfun; Ozdemir, Ercan; Filiz, Ahmet Kemal; Taskiran, Ahmet Sevki; Gursoy, SinanGhrelin, a peptide hormone released from the gastric endocrine glands, shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not yet been elucidated. The purpose of this study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [D-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adult rats (weighing approximately 220-240 g) were used in the experiments. To induce morphine tolerance, a three-day cumulative dose regimen was used in the rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg.kg(-1)), [D-Lys3]-GHRP-6 (10 mg.kg(-1)), and morphine (5 mg.kg(-1)) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [D-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Furthermore, co-administration of hexarelin and morphine increases the analgesic effect. In condusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.
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