Person: ARICIOĞLU, FEYZA
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ARICIOĞLU
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FEYZA
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Publication Metadata only Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study(2022-08-01) BİNGÖL ÖZAKPINAR, ÖZLEM; ARICIOĞLU, FEYZA; AKSOY N., Sen E., Sukmasari S., BİNGÖL ÖZAKPINAR Ö., ARICIOĞLU F., YÜCEL Y. Y., Dumlu M. R., Doolaanea A. A., AbdulRahman M. N., OLGAÇ N. V., et al.Purpose The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. Method Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 mu L of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. Results The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. Conclusion The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.Publication Metadata only alpha 7 nicotinic receptor agonist and positive allosteric modulators differently improved schizophrenia-like cognitive deficits in male rats(ELSEVIER, 2021) ARICIOĞLU, FEYZA; Unal, Gokhan; Sirvanci, Serap; Aricioglu, FeyzaThe majority of schizophrenia patients have cognitive deficits as a separate symptom cluster independent of positive or negative symptoms. Current medicines, unfortunately, cannot provide clear benefits for cognitive symptoms in patients. Recent findings showed decreased alpha 7 nicotinic acetylcholine receptor (nAChR) expressions in subjects with schizophrenia. alpha 7 nAChR full/partial agonists and positive allosteric modulators (PAMs) may be valuable drug candidates to treat cognitive deficits of disease. This study comparatively investigated the effect of alpha 7 nAChR agonist (A-582941), type I PAM (CCMI), type II PAM (PNU-120596), and the antipsychotic drug (clozapine) on behavioral, molecular, and immunohistochemical parameters in a subchronic MK-801 model of schizophrenia in male rats. Novel object recognition (NOR) and Morris water maze (MWM) tests were performed to evaluate recognition and spatial memories, respectively. Gene and protein expressions of parvalbumin, glutamic acid decarboxylase-67 (GAD67), and alpha 7 nAChR were examined in the rats' hippocampal tissue. The subchronic MK-801 administration produced cognitive deficits in the NOR and MWM tests. It also decreased the protein and gene expressions of parvalbumin, GAD67, and alpha 7 nAChR in the hippocampus. Clozapine, A-582941, and PNU-120596 but not CCMI increased the parvalbumin and alpha 7 nAChR expressions and provided benefits in recognition memory. Interestingly, clozapine and CCMI restored the MK-801 induced deficits on GAD1 expression and spatial memory while A-582941 and PNU-1 20 596 were ineffective. These results indicated that alpha 7 nAChR agonist, type I and type II PAMs may provide benefits in different types of cognitive deficits rather than a complete treatment in schizophrenia.Publication Open Access NLRP1-Mediated Antidepressant Effect of Ketamine in Chronic Unpredictable Mild Stress Model in Rats(KOREAN NEUROPSYCHIATRIC ASSOC, 2020-04-15) ARICIOĞLU, FEYZA; Aricioglu, Feyza; Yalcinkaya, Canan; Ozkartal, Ceren Sahin; Tuzun, Erdem; Sirvanci, Serap; Kucukali, Cem Ismail; Utkan, TijenObjective NOD-like receptor protein 1 (NLRP1) inflammasome complex has been recently associated with chronic unpredictable mild stress (CUMS) model of depression. Our aim was to investigate whether ketamine-induced antidepressant effect is associated with suppression of NLRP1. Methods Wistar albino rats were divided into control, CUMS, CUMS+acute ketamine (a single 10 mg/kg dose) and CUMS+chronic ketamine (daily 10 mg/kg injections for 3 weeks) groups (n=10 for each group). Sucrose preference test and forced swimming test were performed to assess anhedonia and immobility time respectively for the severety of depression symptoms. Brain tissues were dissected and prefrontal cortex and hippocampus regions were used for real-time polymerase chain reaction (PCR) and immunohistochemical analysis. Results CUMS procedure significantly induced depressive-like symptoms whereas both acute and chronic ketamine treatment ameliorated them. mRNA expression levels of NLRP1, caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), NF-kappa B, endothelial nitric oxide synthase, IL-1 beta, IL-6, toll-like receptor 4 (TLR-4) and purinergic 2x7 receptor (P2X7R) and numbers of Iba-1+and GFAP+glial cells were reduced by acute and/or chronic ketamine treatment. Conclusion In the present study for the first time upstream and downstream elements of the NLRP1 inflammasome complex are shown to be suppressed by ketamine thus reinforcing the involvement of NLRP1 in the physiopathology of depression.Publication Open Access Microglial activation mediates maternal separation-induced depressive-like behavior in rats: A neurodevelopmental depression model(2023-04-01) ARICIOĞLU, FEYZA; Yurtdas C., Zortul H., Yilmaz B., ARICIOĞLU F.© 2023 The AuthorsBackground: : Maternal Separation (MS) is an early life stress which has been associated with neurological, behavioral, chemical and endocrinological changes in adult life in rats and both short term and long-term mental health disturbances, notably depression in human. This study was planned as a neurodevelopmental depression model, to investigate the possible role of the NLRP3 pathway. Material and Method: : Rat pups were separated from their mothers on their second postnatal day (PND) for 4 h and were placed back in their home cage every day for 21 days. On PND23 they were randomly assigned to either the MS or the MS + imipramine group (receiving 30 mg/kg/day i.p. imipramine for 15 days). Depression-like behaviors were assessed by open field, sucrose preference, forced swimming and elevated plus maze tests. Prefrontal cortex regions were dissected to evaluate NLRP3, ASC and caspase-1 mRNA expressions. Results: : Significant decrease of total activity, sucrose preference as an anhedonia indicator, longer immobilization time in the forced swim test, increased time and the number of entries into the closed arms in elevated plus maze were found in the MS group compared to Control group, and these effects were reversed by imipramine treatment. NLRP3, ASC and caspase-1 mRNA expressions were increased with MS and this increase was suppressed with imipramine treatment. Conclusion: : MS causes depressive-like behaviors in rats and these behavioral changes may be related to the NLRP3 pathway. Imipramine treatment can prevent not only depression-like behaviors, but also neuroinflammation by suppressing NLRP3-mediated mechanisms in the neurodevelopmental depression process.Publication Metadata only Alpha 7 nicotinic receptor agonist and positive allosteric modulators improved social and molecular deficits of MK-801 model of schizophrenia in rats(PERGAMON-ELSEVIER SCIENCE LTD, 2020) ARICIOĞLU, FEYZA; Unal, G.; Bekci, H.; Cumaoglu, A.; Yerer, M. B.; Aricioglu, F.Schizophrenia is a common psychiatric disease that cannot be fully treated with current antipsychotic drugs. It has shown that glutamatergic NMDA receptor antagonists such as MK-801 cause schizophrenia-like phenotype in rodents. Recent studies indicated that alpha 7 nicotinic acetylcholine receptor (nAChR) deficits contribute to schizophrenia. Enhancing its activity with agonist or positive allosteric modulators (PAMs) may be a valuable approach for treatment. The certain intracellular pathways such as Akt/Glycogen synthase kinase 3 beta (GSK-3 beta) and phosphodiesterase-4 (PDE-4)/cAMP are associated with the pathogenesis of schizophrenia. In this study, we examined the effect of alpha 7 nAChR agonists and PAMs on the behavioral and molecular phenotype of schizophrenia in the subchronic MK-801 administered rats. Social interaction, the levels of alpha 7 nAChR, and related intracellular pathways (cAMP, PDE4A, PDE4D, p-Akt/Akt, p-GSK-3 beta/GSK-3 beta) were measured by behavioral or ELISA and western blot tests. Subchronic MK-801 administration decreased the following behaviors and increased the avoiding behaviors. However, only alpha 7 nAChR agonist (A-582941) increased the following behavior while alpha 7 nAChR agonist, PAMs (CCMI and PNU-120596), and clozapine decreased the avoiding behavior compared to MK-801. For molecular parameters, MK-801 administration decreased the alpha 7 nAChR, p-Akt/Akt, p-GSK-3 beta/GSK-3 beta expressions, and cAMP levels while it increased PDE4A, PDE4D expressions in the prefrontal cortex. Besides, MK-801 decreased the alpha 7 nAChR, p-GSK-3 beta/GSK-3 beta expressions in the hippocampus. We found clozapine, alpha 7 nAChR agonists, and PAMs reversed the molecular deficits induced by MK-801. Herein, we showed that prefrontal cortex is more sensitive to the devastating effects of subchronic MK-801 administration, especially for PDE4, in rats. In addition to clozapine, alpha 7 nAChR agonists and PAMs found to be beneficial on both social and molecular deficits induced by MK-801 in rats. We suggested that alpha 7 nAChR agonists and PAMs might be valuable approaches to treat negative symptoms of schizophrenia when unmet needs and current limitations considered in this pathology.Publication Open Access Cannabinoids and neuroinflammation: Therapeutic implications(2023-04-01) ARICIOĞLU, FEYZA; Leonard B. E., ARICIOĞLU F.This review summarizes the pharmacological properties of tetrahydrocannabinol (THC) and cannabidiol (CBD), cannabinoid components of several species of herbal cannabis. The pharmacological effects of the phytocannabinoids have been extensively investigated and the importance of the cannabinoid receptors (CB1 and CB2) on immune cells has provided important information on the intracellular targets for these molecules. In addition to the phytocannabinoids, endogenous cannabinoids also exist in the form of anadramide and 2-srodolylglycerol (2-AG). These, together with their synthesizing and metabolizing enzymes, form the cannabinoid system. Since the discovery of the endocannabinoid system and the role that neuroinflammation plays in neurological and psychiatric illness, the potential therapeutic importance of this system has been of growing interest. In addition, the need to develop drugs which specifically target the CB1 and CB2 receptors has been stimulated by the pharmacological complexity of both THC and CBD. This review briefly summarizes the therapeutic potential of the naturally occurring and the synthetic cannabinoids which will need to be developed, if such drugs are to fulfill the therapeutic promise which the cannabinoids offer.Publication Metadata only Agmatine has beneficial effect on harmaline-induced essential tremor in rat(ELSEVIER IRELAND LTD, 2021) ARICIOĞLU, FEYZA; Akman, Ozlem; Utkan, Tijen; Aricioglu, Feyza; Gullu, Kemal; Ates, Nurbay; Karson, AyseEssential tremor (ET) is one of the most prevalent movement disorders and the most common cause of abnormal tremors. However, it cannot be treated efficiently with the currently available pharmacotherapy options. The pathophysiology of harmaline-induced tremor, most commonly used model of ET, involves various neurotransmitter systems including glutamate as well as ion channels. Agmatine, an endogenous neuromodulator, interacts with various glutamate receptor subtypes and ion channels, which have been associated with its? beneficial effects on several neurological disorders. The current study aims to assess the effect of agmatine on the harmaline model of ET. Two separate groups of male rats were injected either with saline or agmatine (40 mg/ kg) 30 min prior to single intraperitoneal injection of harmaline (20 mg/kg). The percent duration, intensity and frequency of tremor and locomotor activity were evaluated by a custom-built tremor and locomotion analysis system. Pretreatment with agmatine reduced the percent tremor duration and intensity of tremor induced by harmaline, without affecting the tremor frequency. However, it did not affect the decreased spontaneous locomotor activity due to harmaline. This pattern of ameliorating effects of agmatine on harmaline-induced tremor provide the first evidence for being considered as a treatment option for ET.Publication Open Access The effect of maternal separation stress-induced depression on ovarian reserve in Sprague Dawley Rats: The possible role of imipramine and agmatine through a mTOR signal pathway(2023-10-01) ARICIOĞLU, FEYZA; Önel T., ARICIOĞLU F., Yıldırım E., Zortul H., Yaba A.Purpose: To examine the possible role of impramine and agmatine through a mTOR signal pathway on rat ovary after maternal separation stress-induced depression. Methods: Sprague Dawley neonatal female rats were divided into control, maternal separation (MS), MS+imipramine, and MS+agmatine groups. Rats were subjected to MS for 4 hours daily from postnatal day (PND) 2 to PND 21 and pups were exposed to social isolation (SI) on PND23 for 37 days for model establishment treated with imipramine (30 mg/kg; ip) or agmatine (40 mg/kg; ip) for 15 days. In order to examine behavioral changes rats were all subjected to locomotor activity and forced swimming tests (FST). Ovaries were isolated for morphological evaluation, follicle counting and mTOR signal pathway protein expression levels were detected. Results: Increased number of primordial follicles and diminished ovarian reserve in the MS groups were detected. Imipramine treatment caused diminished ovarian reserve and atretic follicle; however, agmatine treatment provided the maintenance of ovarian follicular reserve after MS. mTOR signal pathway may have an important role during rat ovarian follicular development in model of MS. Conclusions: Our findings suggest that agmatine may help to protect ovarian reserve during follicular development by controlling cell growth.Publication Open Access The possible role of NLRP3 inflammasome in depression and myocardial infarction comorbidity(2023-09-01) BAYSAK, ERENSU; YILDIRIM, ÇAĞAN; SAYAR, NURTEN; SAYAR, MUSTAFA KEMAL; ARICIOĞLU, FEYZA; BAYSAK E., Yildirim C., SAYAR N., SAYAR M. K., Halaris A., ARICIOĞLU F.It is well-established that cardiovascular disease and depression are highly comorbid. This study aimed to assess the possible role of the NOD-like receptor protein 3 (NLRP3) inflammasome pathway and the high-sensitivity C-reactive protein (hsCRP) in patients with incident myocardial infarction in the presence or absence of depression. Sixty-eight consecutive patients with incident ST-elevation myocardial infarction and twenty healthy subjects were included. The patients were assessed using the Structured Clinical Interview for DSM-5 Disorders—Clinician Version during their 1–4-day-long hospitalization and were divided into two groups: with and without comorbid depression. Blood samples for the determination of NLRP3, interleukin-18 (IL-18), interleukin-1β (IL-1β), and hsCRP levels were analyzed using ELISA. NLRP3, IL-1β, IL-18, and hsCRP levels were significantly higher in myocardial infarction patients compared to the healthy group (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). No significant difference was found between the myocardial groups with and without depression. However, in the logistic regression analysis, the NLRP3 variable in myocardial infarction patients was found to have a significant contribution to the likelihood of depression (p = 0.015, OR = 1.72, and CI = 1.11–2.66). The likelihood of depression is associated with increasing NLRP3 levels in myocardial infarction patients. However, this potential role should be further explored in a larger sample.