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Öğe Akut ve Kronik Kanabinoid Uygulamasının Sıçan Beyin Bölgelerinde Nosiseptin/Orfanin FQ Düzeyleri Üzerine Etkisi ve Antinosiseptif Etkisine Tolerans Gelişimi ile İlişkisi(2014) Karadağ, Çetin Hakan; Todurga, Zeynep Gizem; Kızılay, Gülnur Özfidan; Topuz, Ruhan Deniz; Gunduz, Ozgur; Duvan, Kübra Aydemir; Ulugöl, Ahmet[Abstract Nıt Available]Öğe Anti-Inflammatory and Antipruritic Effects of Remote Ischaemic Postconditioning in a Mouse Model of Experimental Allergic Contact Dermatitis(Mdpi, 2023) Gunduz, Ozgur; Sapmaz-Metin, Melike; Topuz, Ruhan Deniz; Kaya, Oktay; Karadag, Cetin Hakan; Ulugol, AhmetBackground and Objectives: Allergic contact dermatitis is a common type IV hypersensitivity reaction characterised by redness, itching, oedema and thickening of the skin. It occurs in about 7% of the population and its incidence is increasing. It has been observed that the preconditioning of tissues by exposing them to transient ischemia increases resistance to subsequent permanent ischemia, and this phenomenon is called ischemic preconditioning. It has been shown that conditioning in one organ can also protect other organs. The protective effect of remote ischemic preconditioning is thought to be based on the induction of anti-inflammatory responses. The aim of this project was to investigate the anti-inflammatory and antipruritic effects of remote ischemic postconditioning in a mouse model of experimental allergic contact dermatitis. Methods: Experimental allergic contact dermatitis was induced with 1-fluoro-2,4-dinitrobenzene. Remote ischemic postconditioning was performed at 3 and 25 h after the challenge. Ear thickness and number of scratches 24 and 48 h after challenge, as well as cytokine levels and the infiltration of mast cells, neutrophils, CD4(+) and CD8(+ )T lymphocytes in serum and ear tissue at 48 h were measured to determine the effect of RIPsC. Results: Remote ischemic postconditioning decreased ear thickness, one of the symptoms of allergic contact dermatitis (p < 0.0001). It had no significant effect on the number of scratches. It reduced serum IL-17 levels (p < 0.01). It alleviated local inflammation by suppressing CD8+ T lymphocyte and neutrophil infiltration. Conclusions: It was concluded that remote ischemic postconditioning may alleviate the symptoms of allergic contact dermatitis by suppressing CD8(+ )T lymphocyte and neutrophil infiltration and reducing IL-17 secretion.Öğe Atriyal natriüretik peptid infüzyonunun izole sıçan kalbinde iskemi sonrası oluşturduğu hemodinamik değişikliklerde egzersizin rolü(2015) Vardar, Selma Arzu; Palabıyık, Orkide; Yalta, Tülin; Özen, Serap Topçu; Guksu, Zuhal; Topuz, Ruhan Deniz; Karadağ, Çetin HakanBu çalışmada düşük akımlı iskemi sonrası reperfüzyon döneminde atriyal natriüretik peptid (ANP) uygulamasının sol ventrikül hemodinamik yanıtlarına etkisi ve bu etkide egzersizin rolü araştırıldı. Gereç ve yöntem: Çalışmada yer alan tüm sıçanlara 60 dakika düşük akımlı iskemi ve takiben 120 dk reperfüzyon uygulandı. Egzersiz (E) gruplarına ardışık olarak beş gün süreyle yürüyüş egzersizini takiben iskemi ve reperfüzyon uygulandı. Reperfüzyonun ilk 15 dakikasında 0.1 ?M/L ANP infüzyonu yapılan iki grup; ANP (n=6) ve Egzersiz-ANP (n=6) gruplarını oluşturdu. Tüm gruplarda sol ventrikül gelişim basıncı (SVGB), maksimum ve minimum sol ventrikül basınç değişim oranları (+dP/dt and -dP/dt) kaydedildi. Bulgular: Kontrol (K), E, ANP ve E-ANP gruplarının SVGB, +dp/dt, -dp/dt ve kalp hızı değerleri iskemi öncesinde ve iskemi sonrası reperfüzyonun 1, 60 ve 120. dakikalarında karşılaştırıldığında gruplar arasında istatistiksel olarak anlamlı bir farklılık göstermedi. Benzer şekilde infarkt alanlarının yüzde değerleri karşılaştırıldığında dört grup arasında istatistiksel olarak anlamlı farklılık bulunmadı. Sonuç: Kısa süreli yoğun egzersiz, reperfüzyon döneminde ANP uygulamasına bağlı kardiyak kontraktilitede oluşan değişimleri etkilememektedirÖğe Cannabinoid Receptors Are Not Involved in Antinociception Induced by Systemic Diclofenac in Mice(Trakya Üniversitesi, 2020) Chatzisali, Beiza; Gaş, Tolga; Kılgın, Hilmi; Aydemir, Kübra Duvan; Erümit, Dilşat; Topuz, Ruhan Deniz; Ulugöl, AhmetAims: It has been long suspected that the cannabinoid system participates in the antinociceptive effects of nonsteroidal anti-inflammatory drugs. We studied the possible effects of cannabinoid receptor antagonism on diclofenac-induced antinociceptionin the writhing test in mice. Methods: In our study, male BALB/c mice, weighing 20-30 g, were used. Writhing responses wereproduced by intraperitoneal injection of 0.6% acetic acid. Different doses of diclofenac (3, 10, 30 mg/kg, i.p.) were tested, thenthe influence of AM-251 (1 mg/kg, i.p.), a cannabinoid CB1 receptor antagonist and AM-630 (3 mg/kg, i.p.), a cannabinoidCB2 receptor antagonist on the antinociceptive effects of diclofenac was studied. Results: Diclofenac administration elicited asignificant, dose-dependent antinociceptive response; however, neither the cannabinoid CB1 receptor antagonist AM-251 northe cannabinoid CB2 receptor antagonist AM-630 had any influence on the antinociceptive effect of diclofenac. Conclusion:Iinhibition of cannabinoid receptors does not contribute to the antinociceptive action of systemic diclofenac. Further studiesare needed to explain the antinociceptive mechanism of diclofenac. Keywords: AM-251, AM-630, antinociception, cannabinoidreceptors, diclofenacÖğe Could serum endocannabinoid and N-acylethanolamine levels be important in bipolar disorder?(Taylor & Francis Ltd, 2023) Topuz, Ruhan Deniz; Gorgulu, Yasemin; Uluturk, Milkibar KyazimObjectives The endocannabinoid system (ECS) is a critical important neuromodulatory system that interacts with many neurohormonal and neurotransmitter systems in the brain. It plays a pivotal role in emotional responses and mood regulation. The ECS is related with psychotic disorders, depression, anxiety and autism. In this study, we aimed to investigate whether there is any relationship between endocannabinoid and N-acylethanolamine levels with bipolar disorder. Methods Seventy-nine patients with bipolar disorder diagnosis, who are in the euthymic period, were included in the study. Clinical characteristics, symptoms and serum endocannabinoid and N-acylethanolamine levels were compared. Endocannabinoid and N-acylethanolamine levels were evaluated using liquid chromatography-tandem mass spectrometry. Results In total of 79 patients, 44 (55.69%) were females and 35 (44.30%) were males. The mean age of the patients was 42.40 +/- 1.10 years. Palmitoylethanolamide (PEA) levels were higher and oleoylethanolamide and 2-arachidonyl glycerol levels were lower in patients who had at least one depressive episode during their life-time illness than in patients who had no depressive episode while arachidonyl ethanolamide levels were unchanged Conclusions PEA levels were correlated with the history and frequency of depressive episodes and the history of depressive symptoms in patients with bipolar disorder.Öğe Does dipyrone produce anxiolytic-like effects in mice?(Cukurova Univ, Fac Medicine, 2019) Topuz, Ruhan Deniz; Gunduz, Ozgur; Dokmeci, Dikmen; Karadag, Cetin Hakan; Ulugol, AhmetPurpose: Paracetamol has been shown to exert anxiolytic-like effects mediated by endocannabinoids via cannabinoid CB1 receptors. Dipyrone is an analgesic with similar effects to paracetamol rather than non-steroidal anti-inflammatory drugs. Involvement of central structures to its effects are long under debate, whereas recent findings suggesting contribution of cannabinoid CB1 receptors to its antinociceptive effect support this argument. Taken together, the purpose of this study was to investigate whether dipyrone possesses anxiolytic-like behavior; contribution of cannabinoid CB1 and CB2 receptors and TRPV1 receptors will be determined in case of observing any effect of dipyrone in anxiety tests. Material and Methods: Balb-c mice effects of dipyrone (150, 300, 600 mg/kg, i.p) were assessed in three-chamber social interaction, open-field, elevated plus-maze and rota rod tests. The cannabinoid CB1 antagonist AM251 (1 mg/kg i.p.), the CB2 antagonist SR 144528 (1 mg/kg i.p.) and the TRPV1 antagonist capsazepine (3 mg/kg i.p) were going to be administered before dipyrone injections if any effect of dipyrone occurs. Results: Dipyrone had no effect at any dose in behavioral tests (three-chamber social interaction, open-field, elevated plus-maze and rota rod tests). Therefore, dipyrone is not tested together with the cannabinoid CB1 and CB2 antagonists and the TRPV1 receptor antagonist. Conclusion: Unlike paracetamol, dipyrone did not possess anxiolytic-like effects in mice. Discrepancies in experimental models and methodologies may be the reason of our results.Öğe Does Oral Monosodium Glutamate Have a Cochleotoxic Effect? An Experimental Study(Karger, 2022) Guven, Selis Gulseven; Ersoy, Onur; Topuz, Ruhan Deniz; Bulut, Erdogan; Kizilay, Gulnur; Uzun, CemIntroduction: The effect of orally consumed monosodium glutamate (MSG), which is a common additive in the food industry, on the cochlea has not been investigated. The present study aimed to investigate the possible cochleotoxic effects of oral MSG in guinea pigs using electrophysiological, biochemical, and histopathological methods. Methods: Thirty guinea pigs were equally divided into control and intervention groups (MSG 100 mg/kg/day; MSG 300 mg/kg/day). At 1 month, 5 guinea pigs from each group were sacrificed; the rest were observed for another month. Electrophysiological measurements (distortion product otoacoustic emission [DPOAE] and auditory brainstem response [ABR]), glutamate levels in the perilymph and blood samples, and histopathological examinations were evaluated at 1 and 2 months. Results: Change in signal-to-noise ratio at 2 months was significantly different in the MSG 300 group at 0.75 kHz and 2 kHz (p = 0.013 and p = 0.044, respectively). There was no statistically significant difference in ABR wave latencies of the guinea pigs given MSG compared to the control group after 1 and 2 months; an increase was noted in ABR thresholds, although the difference was not statistically significant. In the MSG groups, moderate-to-severe degeneration and cell loss in outer hair cells, support cells, and spiral ganglia, lateral surface junction irregularities, adhesions in stereocilia, and partial loss of outer hair cell stereocilia were noted. Conclusion: MSG, administered in guinea pigs at a commonly utilized quantity and route of administration in humans, may be cochleotoxic.Öğe The Effect of Ceftriaxone in Valproic Acid-Induced Mouse Model of Autism(Tabriz Univ Medical Sciences & Health Services, 2022) Gur, Gamze; Topuz, Ruhan Deniz; Kizilay, GulnurPurpose: Autism is a multifactorial neurodevelopment disease and it has not been disclosed as a hypoglutamatergic or hyperglutamathergic disease. Ceftriaxone is an antibiotic that increases glutamate transporter-1 (GLT-1) expression in the brain in chronic use. In our study we aimed to investigate the effects of different doses of ceftriaxone in postnatal period in male mice exposed to valproic acid (VPA) at 12.5th day of pregnancy.Methods: A total of 96 BALB/c male mice were divided into 12 groups (n = 8 animals per group). Ceftriaxone (50, 100, 200 mg/kg/d) or saline was given to the male offsprings born from pregnant mice administered VPA and/or saline, between days 47 and 55. Dihydrokainic acid (10 mg/kg), a GLT-1 inhibitor, was administered intraperitoneally to evaluate whether GLT-1 mediates the effect of ceftriaxone. Three chamber sociability and social interaction test and the rota rod test were performed in all groups on days 54 and 55. GLT-1 levels in the hippocampus were measured by immunohistochemistry (IHC) and western blotting (WB).Results: In our study, autism-like behaviors were observed in male offsprings that were exposed to VPA in the intrauterine period. Chronic ceftriaxone administration has no curative effect on behavioral impairment seen in autism.Conclusion: Our results show that ceftriaxone did not exert significant therapeutic effect on VPA-induced mouse model of autism.Öğe Effect of chronic physiological stress on rat oocyte reserve: Role of IGF-1, AMH and Bcl-2(Natl Inst Science Communication-Niscair, 2023) Ercetin, Deniz; Sapmaz-Metin, Melike; Topuz, Ruhan DenizOvarian activity has a complex physiology and is related to oocyte quality in women. This study investigates the effects of ovarian activity with chronic stress (CS) on behavioural parameters, estrous cycles, and ovarian follicular development in rats. Here, we examined the ovarian microenvironment against exposure to stress and to elucidate the stress-related ovarian molecular mechanisms. Twenty female Sprague-Dawley rats were divided into the control and the CS groups. The estrous cycle phases were detected by vaginal smear. Rats in the CS group were immobilized 1 h/day for 8 weeks. At the end of the experiment, all animals were subjected to behavioral tests in their metestrus phase and sacrificed on the other day (diestrus phase). The ovaries were harvested for histological analysis, blood samples were taken to measure cortisol levels. The immunoreactivities of ovarian IGF-1, AMH and Bcl-2 proteins were evaluated by immunohistochemistry. Here, we have studied CS-induced prolonged estrous cycles. We showed a lower number of developing follicles but the higher number of atretic follicles in the CS group's ovaries. The dominant structure of ovarian histology was large interstitial glands. CS caused decreases in ovarian Bcl-2, IGF-1 and AMH immunoreactivities which have roles in follicular development. Also, anxiety was detected in CS-exposed animals. Our results showed that chronic restrainer stress can be a serious endocrine disrupter by reducing ovarian paracrine factors.Öğe Effect of mitomycin-C applied through different approaches following tracheal surgery on development of granulation tissue and level of nephrotoxicity in rats(Baycinar Medical Publ-Baycinar Tibbi Yayincilik, 2019) Kuzucuoglu, Mustafa; Topuz, Ruhan Deniz; Altun, ErenBackground: This study aims to evaluate the effect of mitomycin-C applied through different drug administration approaches on the development of granulation tissue in the field of surgery and renal functions in rats which underwent tracheal surgery. Methods: Fifty male adult Sprague Dawley rats (weighing mean 200 g to 300 g) were divided into five groups. An incision was performed between the fifth and sixth cartilage ring of the trachea in all groups under anesthesia and the incision was primarily repaired with a 6/0 monofilament absorbable suture. A single dose of mitomycin-C 0.5 mg was applied in the experimental animals appropriate with their assigned groups as topical, intraperitoneal injection, injection to the wound edges, and through inhalation. No mitomycin-C was administered in one group which was accepted as the control group. Rats were sacrificed four weeks after surgery and their tracheas were excised subsequently. Tracheal tissue samples were histopathologically evaluated in terms of epithelization, fibrosis, amount of fibroblasts, angiogenesis, and inflammatory response. Diameter and wall thickness of the tracheas were measured. Blood urea and creatinine levels were evaluated for nephrotoxicity, and the rats were immunohistochemically examined for glomerular pathology. Results: Epithelization was statistically significantly decelerated (p<0.01), diameter of the trachea was statistically significantly larger (p<0.05), and wall thickness of the trachea was significantly thicker in the group with topical mitomycin-C application compared to the control group (p<0.01). Conclusion: Topically applied mitomycin-C following tracheal surgery slows down epithelization and, thus, decreases the development of granulation tissue and maintains a wider diameter of the trachea.Öğe Effects of hippocampal histone acetylation and HDAC inhibition on spatial learning and memory in the Morris water maze in rats(Wiley, 2020) Topuz, Ruhan Deniz; Gunduz, Ozgur; Tastekin, Ebru; Karadag, Cetin HakanIn recent years, it has been pointed out that epigenetic changes affect learning and memory formation. Particularly, it has been shown that histone acetylation and DNA methylation work in concert to regulate learning and memory formation. We aimed to examine whether acetylation of H2B within the rat hippocampus alters by trainings in the Morris water maze test. Male, 2-3 months old, Sprague Dawley rats were trained in Morris water maze task. Animals were given four trials per day for five consecutive days to locate a hidden platform. On the sixth day, the platform was removed and the animals were swum for 60 s. The effects of sodium butyrate, histone deacetylase inhibitor, were tested on normal and scopolamine-induced memory-impaired rats. The histone deacetylase inhibitor, sodium butyrate, increased histone H2B acetylation in normal rats. Sodium butyrate had no effect on learning and memory performance of normal rats; however, it partially ameliorated learning and memory disruption induced by scopolamine. So, the histone deacetylase inhibitors can be new treatment agent for cognitive disorders.Öğe Effects of in vitro Amitriptyline, Fluoxetine, Tranylcypromine and Venlafaxine on Saphenous Vein Grafts(Soc Brasil Cirurgia Cardiovasc, 2019) Akinci, Melek; Karadag, Cetin Hakan; Huseyin, Serhat; Oltulu, Cagatay; Canbaz, Suat; Gunduz, Ozgur; Topuz, Ruhan DenizObjective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3x10(-6)M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10(-11)-3x10(-5)M, while venlafaxine was added in the range of 10(-9)-3x10(-5)M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.Öğe Endocannabinoid and N-acylethanolamide levels in rat brain and spinal cord following systemic dipyrone and paracetamol administration(Canadian Science Publishing, 2019) Topuz, Ruhan Deniz; Gunduz, Ozgur; Karadag, Cetin Hakan; Dokmeci, Dikmen; Ulugol, AhmetThe cannabinoid system has been suspected to play a role in the mechanisms of action of dipyrone and paracetamol. Our purpose was to measure the local endocannabinoid and N-acylethanolamide levels in the brain and spinal cord of rats following dipyrone and paracetamol administration. Nociception was assessed 1, 5, and 12 h following drug injections in Wistar rats, using tail-flick and hot-plate tests. The antinociceptive effects of dipyrone (150, 300, and 600 mg/kg, i.p.) and paracetamol (30, 100, and 300 mg/kg, i.p.) were observed. After administration of the highest doses of dipyrone and paracetamol, endocannabinoid (N-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG)) and N-acylethanolamide (palmitoylethanolamide (PEA), oleoylethanolamide (OEA)) levels were measured in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cords of rats using tandem mass spectrometry with liquid chromatography. Increased 2-AG levels were observed in the PAG and the RVM 12 h after paracetamol injection; dipyrone exerted no action on 2-AG levels. Analgesic administrations led to a reduction in AEA levels in the RVM and spinal cord; similar decreases in PEA and OEA levels were observed in the RVM and the spinal cord. Dipyrone and paracetamol administrations appear to exert complicated effects on endocannabinoid and N-acylethanolamide levels in rats.Öğe Farelerde sinir zedelenmesi ile oluşan allodini üzerine sentetik kannabionid WIN 55,212-2 ile noradranalin geri-alım ınhibitörü maprotilin etkileşimi: Bir ızo(2014) Topuz, Ruhan Deniz; Karadağ, Çetin Hakan; Ulugöl, Ahmet; Ürek, Özlem; Gunduz, Ozgur[Abstract Nıt Available]Öğe FARELERDE SKOPOLAMİNLE BOZULMUŞ ÖĞRENME VE BELLEK ÜZERİNENÖROTENSİN AGONİSTİ PD149163’ÜN ETKİSİ(2021) Kaya, Oktay; Topuz, Ruhan DenizNörotensin (NT), santral sinir sisteminde nöromodülatör, nörotransmitter ve nörohormon olarak görev yapan bir tridekapeptittir. NT; vücut sıcaklığının düzenlenmesi, ağrı, motor aktivite, öğrenme ve bellek yapılanması gibi fizyolojik süreçlerde rol oynar. Bu çalışmada NT agonisti PD149163’ün akut ve kronik kullanımının skopolaminle oluşturulmuş bellek bozukluğu üzerine etkilerinin incelenmesi amaçlandı. Bu çalışma Trakya Üniversitesi Hayvan Deneyleri Yerel Etik kurulundan 2019.02.01 karar no ile onaylanmıştır. Çalışmada toplam 32 adet Balb/c türü erişkin erkek fare 4 gruba ayrıldı. Öğrenme ve bellek fonksiyonları Morris su labirenti testinde değerlendirildi. 7 gün boyunca skopolamin (1 mg/kg i.p.) uygulandıktan sonra akut ve kronik (7 gün, 4 mg/kg, i.p) PD149163 tedavisinin öğrenme ve bellek bozukluğunu geri döndürüp döndürmediği incelendi. Çalışmada yüzme eğitimlerinden elde edilen veriler, tekrarlayan ölçümler iki yönlü varyans analizi (ANOVA ) ile analiz edildi. Probe verileri tek yönlü varyans analizi ile değerlendirildi. Kronik PD149163 uygulamasının Morris su labirenti testinde ne öğrenme fazında ne de bellek fazında iyileştirici bir etkisi olmadı. Akut PD149163 uygulamasının skopolaminle oluşturulmuş bellek bozukluğu üzerine herhangi bir etkisi olmadı. Çalışmamızda NT agonistinin skopolaminle oluşturulan öğrenme ve bellek bozukluğunda düzeltici etkisi görülmemiştir. NT reseptörleri yeni ilaç hedefleri olarak değerlendirilmelerine karşın bu alanda yapılacak çok fazla sayıda çalışmaya ihtiyaç olduğu düşüncesindeyiz.Öğe Hemodynamic efects of atrial natriuretic peptide in ischemia-reperfusion injury that occurs afer exercise(2015) Vardar, Selma Arzu; Palabıyık, Orkide; Topuz, Ruhan Deniz; Gürel, Elif Ezgi; Çalışkan, Semra; Topçu, Serap Özen; Süt, NecdetBackground/aim: Atrial natriuretic peptide (ANP) is known as a protective agent against ischemia-reperfusion injury for cardiomyocytes.We compared the hemodynamic efects of ANP and isatin, which is known as an ANP receptor blocker, in ischemia followed byreperfusion in exercised rat hearts with nonexercised ones.Materials and methods: Isolated hearts were perfused in 4 exercised (E) groups afer a running protocol for 5 days and 4 nonexercised(NE) groups. In the frst protocol, ANP was added to the perfusion solution before ischemia in an E and NE group. In the secondprotocol, diferent doses of isatin (0.1, 10, 100 µM/L) were added to the perfusion solution before ANP in 3 E and 3 NE groups. Lefventricular developed pressure (LVDP) and maximum and minimum rates of change in lef ventricular pressure (dP/dtmax and dP/dtmin) were recorded.Results: Higher LVDP and dP/dtmin values were observed in the E group than the NE group following addition of ANP before ischemia.Values of dP/dtmax were higher in the E group at the frst minute of reperfusion period. Hemodynamic diference was not observedbetween groups given the same amount of isatin before ANP.Conclusion: Tis study indicated that higher ANP concentrations before ischemia were more efective on the lef ventricle contractilityand relaxation functions in the hearts that were exposed to exercise.Öğe Hemodynamic effects of atrial natriuretic peptide in ischemia-reperfusion injury that occurs after exercise(Tubitak Scientific & Technological Research Council Turkey, 2015) Vardar, Selma Arzu; Palabiyik, Orkide; Topuz, Ruhan Deniz; Gurel, Elif Ezgi; Caliskan, Semra; Topcu Ozen, Serap; Sut, NecdetBackground/aim: Atrial natriuretic peptide (ANP) is known as a protective agent against ischemia-reperfusion injury for cardiomyocytes. We compared the hemodynamic effects of ANP and isatin, which is known as an ANP receptor blocker, in ischemia followed by reperfusion in exercised rat hearts with nonexercised ones. Materials and methods: Isolated hearts were perfused in 4 exercised (E) groups after a running protocol for 5 days and 4 nonexercised (NE) groups. In the first protocol, ANP was added to the perfusion solution before ischemia in an E and NE group. In the second protocol, different doses of isatin (0.1, 10, 100 mu M/L) were added to the perfusion solution before ANP in 3 E and 3 NE groups. Left ventricular developed pressure (LVDP) and maximum and minimum rates of change in left ventricular pressure (dP/dtmax and dP/dtmin) were recorded. Results: Higher LVDP and dP/dtmin values were observed in the E group than the NE group following addition of ANP before ischemia. Values of dP/dtmax were higher in the E group at the first minute of reperfusion period. Hemodynamic difference was not observed between groups given the same amount of isatin before ANP. Conclusion: This study indicated that higher ANP concentrations before ischemia were more effective on the left ventricle contractility and relaxation functions in the hearts that were exposed to exercise.Öğe Morris su labirenti uzaysal öğrenme ve bellek modelinde, sıçan hipokampüsündte histon asetilasyonu ve histon deasetilaz inhibitörünün etkisi(Trakya Üniversitesi Sağlık Bilimleri Enstitüsü, 2015) Topuz, Ruhan Deniz; Karadağ, Çetin HakanSon yıllarda, epigenetik değişikliklerin öğrenme ve bellek oluşumunu etkilediğine dikkat çekilmektedir. Özellikle histon asetilasyonu ve DNA metilasyonunun öğrenme ve bellek oluşumunu birlikte düzenlediği gösterilmiştir. Bu çalışmada Morris su labirentindeki eğitimler sırasında sıçanların hipokampüsünde meydana gelen H2B asetilasyon değişiminin ve histon deasetilaz inhibitörü sodyum bütiratın öğrenme ve bellek üzerine etkisinin incelenmesi amaçlandı. İmmunhistokimyasal incelemede hipokampüs CA1 bölgesinde H2B asetilasyonunun, yüzme eğitimlerinin erken evrelerinde (1. ve 2. günler) arttığı saptandı. Sodyum bütiratın normal sıçanlarda öğrenme ve bellek performansını etkilemediği, ancak skopolamin verilerek performansı bozulan sıçanlarda bu bozulmayı kısmi olarak düzelttiği saptandı. Elde edilen sonuçlar H2B’nin asetilasyonunun öğrenmenin ilk evrelerinde rol oynadığını ve deasetilasyonun inhibe edilmesinin öğrenme ve bellek üzerine kısmi bir etkisi olduğunu göstermektedir.Öğe Non-opioid Analgesics and the Endocannabinoid System(2020) Topuz, Ruhan Deniz; Gündüz, Özgür; Karadağ, Çetin Hakan; Ulugöl, AhmetNon-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as “non-opioid analgesics” and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release.Öğe The role of endocannabinoid system and TRPV1 receptors in the antidepressant and anxiolytic effects of dipyrone in chronic unpredictable mild stress in mice(Elsevier, 2021) Topuz, Ruhan Deniz; Cetinkaya, Mehmet Zahid; Erumit, Dilsat; Aydemir, Kubra Duvan; Gunduz, Ozgur; Karadag, Cetin Hakan; Ulugol, AhmetAlthough dipyrone is a widely used analgesic and antipyretic, its mechanism of action is not fully clarified. Recent studies have drawn attention to its central effects and its relationship with the endocannabinoid system. The endocannabinoid system plays important roles in processes such as anxiety, depression, fear, and learningmemory. In this study, we aimed to investigate whether endocannabinoid levels change in the amygdala in chronic unpredictable mild stress model in mice and whether cannabinoid and TRPV1 receptors mediate antidepressant and anxiolytic effects of dipyrone. Mice were submitted to chronic unpredictable mild stress protocol of 6-weeks, then behavioral test were performed. In the first part of the study, dipyrone was injected at doses of 150, 300, and 600 mg/kg (i.p.) during behavioral tests. In the second part, the CB1 antagonist AM 251 (1 mg/kg, i.p.), the CB2 antagonist AM630 (1 mg/kg, i.p.), and the TRPV1 antagonist capsazepine (3 mg/kg, i.p.) were administered alone or in combination with 300 mg/kg dipyrone to observe if these receptors mediate dipyrone effects. Endocannabinoid and N-acylethanolamines levels were measured by LC-MS/MS in amygdala. Our results showed that there were no changes in AEA, 2-AG, PEA, OAE levels in the amygdala in mice exposed to chronic unpredictable mild stress model; dipyrone exerted antidepressant and anxiolytic effects at doses of 300 and 600 mg/kg; its anxiolytic effect appears to be mediated via CB1 receptors, whereas TRPV1 receptors seems to mediate its antidepressant action.
