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Öğe Alterations in aquaporin gene expression level on cyclophosphamide-induced cardiac injury and possible protective role of Ganoderma lucidum(Springer, 2021) Öztopuz, Özlem; Coşkun, Özlem; Büyük, BaşakThis research study was conducted to investigate the cardioprotective activity of alcoholic extract of Ganoderma lucidum (GL) against cyclophosphamide (CYP)-induced cardiotoxicity in rats model. Therewithal, the regulation in the expression level of Aquaporin (AQP) water channels in the heart was evaluated. Cardiotoxicity was induced in Wistar rats by administering a singledose injection of CYP (200 mg/kg, i.p.) on the seventh day of the experimental period. GL (500 mg/kg, gavage) was administered daily for seven days. Cardiac alteration following CYP and GL administration was evaluated using electrocardiographic changes, morphological staining, AQP gene expression and western blot analysis. It was observed that the CYP administration significantly (p < 0.001) increased cardiac troponin- I (cTn-I) and elevated the level of creatine kinase isoenzyme MB (CK-MB). Further, rats treated with CYP showed increased expression levels of AQP-3, -4 and − 7 compared to the control group. The treatment with GL significantly (p < 0.001) reversed the level of cardiac biomarkers in CYP-induced cardiotoxicity. Potential cardioprotective effect of GL which reduced the severity of cellular damage of the myocardium was supported by histopathological examination. The biochemical, expressional and histopathological reports supported the cardioprotective activity of GL which could be attributed to changes in myocardial edema. To the best knowledge of the authors, this is the first study that reports the cardioprotective role of GL in CYP-induced myocardial edema and the changes in the expression levels of AQP.Öğe Chromatographic Applications in Medicine(2019) Coşkun, Özlem; Öztopuz, ÖzlemChromatography has been preferred in the medical field as one of the most important analytical methods used for the identificationand quantification of a drug and its metabolites in recent years. Various chromatographic techniques have been developed todifferentiate drugs according to their characteristics and interaction types. Among these techniques, particularly High PerformanceAffinity Chromatography (HPAC), Cell Membrane Chromatography (CMC), Mixed Mode Chromatography (MMC), HighPerformance Liquid Chromatography (HPLC) are used for pharmaceutical purposes for bioanalysis of drugs in preclinical and clinicalstudies. The success of Chromatography in the development of rapid and precise analytical methods provides superior specificity andsensitivity in the research of pharmacokinetic properties of drugs in R&D. In personalized medicine, it is important how the dosageand effect of drugs varies from person to person. In recent years, chromotography has been preferred as a promising technique in theanalysis of drug-protein binding and in the examination of clinical or pharmaceutical samples.Öğe Could ARNI have an Effect on LV Fibrosis and Inflammatory Parameters in an Experimental Autoimmune Myocarditis Model?(2022) Duygu, Ali; Gazi, Emine; Deveci, Bülent; Arslan, Mehmet; Öztopuz, Özlem; Adalı, YasemenObjectives: The aim of this study is to investigate the efficacy of sacubitril-valsartan treatment in the early period of\rExperimental Autoimmune Myocarditis (EAM) model, under the perspective of fibrosis and inflammatory cytokines.\rMethods: The study was performed using 18 rats in three groups of EAM (n=6), EAM treatment (n=6) and control (n=6).\rEAM was induced by footpad injections of porcine cardiac myosin and Complete Freund’s Adjuvant (CFA). The EAM group\rwas not given any medical care. 20 mg/kg sacubitril-valsartan was given to EAM treatment (marked as treatment) group\rtwice a day beginning from the 21st day to the 42nd day. No procedure was applied to the control group. Histopathological,\rbiochemical and RT-PCR analyses were performed on the heart tissues taken after the 42nd day of sacrificing.\rResults: Significant congestion, fibrosis, and cellular changes were observed in the EAM and treatment groups. There was\r50% less severe fibrosis,which is 3rd degree, in the Treatment group compared to EAM. Severe congestion rate was lower\rin the treatment group compared to EAM; with the percentage of 16,6% to 50%. Though the average values of treatment\rgroup were lower than EAM group, there was obvious difference in TNF ?, TGF ?1 and NT-proBNP levels (p>0.05) between\rthe EAM and the treatment groups. There was no significant difference in IL-6 levels between the three groups.\rConclusion: In view of findings, the treatment of ARNI in acute autoimmune myocarditis may be promising on cardiac\rrisk markers (cytokine, BNP values) and fibrosis parameters. Studies to be conducted in high-numbered groups will\rreveal more statistical significance.Öğe Effects of Ozone Therapy on Chronic Arsenic Poisoning in Rats(Springer, 2023) Büyük, Başak; Aydeğer, Cemre; Öztopuz, Özlem; Ovalı, Mehmet Akif; Makav, Mustafa; Eroğlu, Hüseyin AvniArsenic (As) is a toxic metalloid that affects many organs through drinking water. This study aims to examine the efficacy of ozone therapy on chronic arsenic toxicity. Twenty-four male Wistar albino rats were housed in individual cages and grouped as control, As, O3, and As + O3. As was applied by adding 5 mg/kg/day in drinking water for 60 days. Ozone therapy was applied at 0.5 mg/kg/day (i.p.) O3 in the last 5 days of the experimental period. Tissues were harvested and analyzed for histopathological injury and apoptotic markers. There was no significant difference between the As + O3 and O3 groups (p = 0.186 and p = 0.599) for light microscopic criteria: inflammatory cell infiltration and hydropic degeneration in liver tissue. In TUNEL assessments, similar outcomes were obtained in the control and As + O3 groups. A statistically significant increase was observed in p53 and Caspase 3 (Casp-3) expression levels in the As group compared to the O3 and As + O3 groups. There was no significant difference between the As + O3 and O3 groups on peritubular hemorrhage and desquamation parameters in kidneys (p = 0.147 and p = 0.094). The KIM-1 expression level was significantly increased in the As group compared to the As + O3 group (p = 0.01), and the Casp-3 expression level was not significantly changed in the O3 group compared to the As + O3 group (p = 0.59). In conclusion, it is determined that ozone therapy has ameliorative effects on the microscopic injury of liver and kidney tissues. In addition to microscopic improvement, KIM-1 gene expression levels were ameliorated in the kidneys. The apoptotic cell counts and the Casp-3 and p53 gene expression levels were decreased by O3 administration. Thus, ozone therapy can be a treatment choice for As toxicity.Öğe Electrophoresis Applications Used in Medicine(E-Journal of New World Sciences Academy, 2020) Coşkun, Özlem; Öztopuz, ÖzlemClinical analysis distinguishing between the characteristics of healthy and pathological conditions, the researcher to solve the mystery of the disease and to provide the treatment of the disease in a short time is very important to save human life. Electrophoresis routine biochemistry, hematology, or urinalysis is one of the basic diagnostic methods commonly used in the world to obtain vitally important information. Nonspecific changes in electrophoretic patterns are associated with patient clinical data electrophoresis, it is very valuable in determining the diseases which cannot be detected by routine diagnostic studies. Many diseases such as liver, renal pathological disorders, inflammation, proteinemia, multiple myeloma, and macroglobulinemia can be diagnosed by electrophoresis. Recent developments in electrophoresis technology will be the miniaturization and portability of systems. With the development of technology, it is possible to perform electrophoresis with programming that enables automatic execution of computerized robotic and electrophoresis protocols. Large research is carried out to improve the systems used by different working groups, especially the automatic electrophoresis system. The methods explored and developed are mainly aimed at increasing the efficiency, reproducibility and accuracy of the separation process. The aim of this review is to emphasize the general features of electrophoresis method, clinical diagnostic applications and future potential.Öğe Genetic polymorphism of BMP-6 gene (rs267196 and rs267192) in patients with ankylosing spondylitis(Refik Saydam National Public Health Agency (RSNPHA), 2019) Öztopuz, Özlem; Sılan, Fatma; Coşkun, Özlem; Akbal, AylaObjective: Bone morphogenetic proteins (BMPs) have been documented to be associated with ankylosing spondylitis (AS) in several populations. The goal of the present study was to determine the association of the (BMP-6) gene polymorphism (rs267192 and rs267196) with AS and to evaluate the relationships between them based on clinical and laboratory data. Methods: This study was conducted during August and November 2013 at the physical therapy and rehabilitation outpatient clinics of çanakkale Onsekiz Mart University Research and Practice Hospital. 42 AS patients and 58 healthy controls were checked with reverse transcription-polymerase chain reaction (RT-PCR) analysis for BMP-6 (rs267192 and rs267196) polymorphism. Clinical data as age, gender, body mass index, C-reactive protein (CRP), erythrocyte sedimentation rate, bath ankylosing spondylitis disease activity index (BASDAI), and HLA-27 positivity were assessed. It was evaluated the relationship between the BMP-6 polymorphism and laboratory findings. Results: The frequencies of AA, AT, and TT genotypes for BMP-6 rs267196 were 9.5% (n=4), 38.1% (n=16), and 52.4% (n=22) in AS patients, and 15.5% (n=9), 44.8% (n=26), and 39.7% (n=23) in controls respectively. BMP-6 rs267196 A allele carriers (versus T ancient allele) had 1.4-fold higher risk and rs267192 T allele carriers (versus C ancient allele) had 1.08-fold higher risk for AS. There was no significant difference between AS and control groups in terms of age, gender and BMI. The CRP and sedimentation levels of the AS group were significantly higher than the control group (p < 0.001). Conclusion: Although some studies have suggested BMP-6 polymorphisms as a possible risk factor for AS, BMP-6, rs267196 and rs267192 alleles were not associated with the disease risk in this study groups. © 2019, Refik Saydam National Public Health Agency (RSNPHA).Öğe Glucagon-like peptide-2 May Assist to Protect against Valproic Acid Induced Hepatic Injury in Rats(2020) Öztopuz, Özlem; Aylanç, Hakan; Şehitoğlu, M.Hilal; Türkön, Hakan; Battal, Fatih; Demir, UfukVPA is widely used in epilepsy and other psychological disorders, increasing the probability of developing non-alcoholic liver diseasein long-term treatments. GLP-2 is a proglucagon belonging to the peptide family expressed in the intestine, pancreas and brain to date.Although there are many studies on the use of GLP-2 for therapeutic purposes on the gastrointestinal system, its effect on liver toxicityis unknown. We aimed to investigate the effect of GLP-2 administration on hepatic function in a rat model with VPA-inducedhepatotoxicity. Rats were injected intraperitoneally at 500 mg/kg and GLP-2 5µg/kg a day. The rats (200-250g) were separated into fourgroups (n=7). Group C was administrated 1 mL of 0.9% SF, Group GLP treated with GLP-2 (5µg/kg/day), Group GLP+VPA werereceived GLP-2 (5µg/kg) 1 h prior to VPA (500 mg/kg), Group VPA received VPA (500 mg/kg), 1 h prior to 1 mL of 0.9% SF ip (n=7).Liver tissues were used to investigate effects of VPA and GLP-2 in the liver 15 days after application. While VPA caused moderate butsignificant liver damage according to biochemical results, mRNA expression of cytokines were found to significantly increase after theday 15. VPA administration significantly induced expression of Interleukin 1 beta (IL-1?), Tumor necrosis factor alpha (TNF-?),Interleukin 10 (IL-10). In contrast, GLP-2 treatment reduced expression of IL-1?, TNF-? and IL-10. Also malondialdehyde (MDA),glutathione s-transferase (?-GST), superoxide dismutase activities (SOD), total antioxidant status (TAS) and total oxidant status (TOS)levels were estimated. GLP-2 had positive effects on both liver enzymes and oxidative stress markers in VPA-induced hepatotoxicity.These results suggest that endogenous GLP-2 administration is associated with a mechanism that moderately protects liver tissue.Öğe Lentinula edodes Ekstraktının Sıçan Karaciğer Dokusu Üzerine İnflamatuar ve Apoptotik Etkisinin Değerlendirilmesi(2020) Coşkun, Özlem; Öztopuz, Özlem; Büyük, BaşakLentinula edodes (Shiitake mantarı) uzak Doğu ülkelerinde binlerce yıldır gıda ve ilaç olarak yetiştirilip kullanılmaktadır. Günümüzdedünya çapında en fazla tüketilen ikinci mantar türüdür. Dünya genelinde 100,000 veya daha fazla mantar türünün 100'den fazlasınıntoksik olduğu tahmin edilmektedir. Mantarlar, dünyanın pek çok yerinde değerli bir gıda maddesidir, ancak bazı türleri insanlardazararlı etkilere neden olabilir, bazı durumlarda potansiyel olarak ölümcül olabilir. Son yıllarda mantar zehirlenmesi ile ilişkili kabuledilen klinik sendromların kapsamı genişlemiştir. Shiitake mantar türünün toksik etkisi konusunda çok az araştırmaya rastlanmış olup,konuyla ilgili bilimsel araştırmalara ihtiyaç vardır. Bu mantar türü yenilebilir, ancak bazı kişilerde küçük yan etkiler veya alerjikreaksiyonlar görülebilir. Literatürde shiitakeye bağlı toksikodermi ve shiitake dermatit vakaları bildirilmiştir. Shiitake mantar sporlarıalerjik reaksiyonlara neden olduğu tespit edilmiştir. Çalışmamızın amacı sıçanlara farklı dozda uygulanan shiitake mantarınınkaraciğer üzerine toksik etkisi olup olmadığını araştırmaktır. Çalışmada sıçanlara farklı dozlarda (düşük ve yüksek dozda) uygulananShiitake mantar ekstraktının karaciğere etkisi; TNF-? (inflamatuar belirteç), Bax, Bcl-2’nin (apoptotik belirteç) ekspresyondeğişimleri incelenerek ve histopatolojik analizleri yapılarak değerlendirildi. Gruplara ait Bax, Bcl-2, TNF-? ekspresyon düzeyleriincelendiğinde Bax ekspresyon seviyesinde düşük doz ile kontrol grubu karşılaştırıldığında anlamlı bir düşüş izlendi (p <0,05). Bcl-2ekspresyon seviyesinde kontrol grubu ve yüksek doz grubu ile karşılaştırıldığında anlamlı bir düşüş izlendi (p <0,05). TNF-?ekspresyon seviyesinde yüksek doz ve kontrol grubu karşılaştırıldığında yine anlamlı bir düşüş izlendi (p <0,05). Histopatolojikolarak gruplarda hidropik dejenerasyon ve sinüzoidal dilatasyon parametreleri değerlendirildi. Hidropik dejenerasyon ve sinüzoidaldilatasyon düşük dozda ve yüksek dozda, kontrol grubuna göre yüksek bulundu. Sonuçlar istatistiksel olarak anlamlı bulundu (p = 0,0ve p = 0,021). Gruplara ait H&E boyama sonrasında Shiitake mantar ekstraktının doza bağlı olarak yapısal değişikliklerde hafifderecede artış saptanmıştır. Literatürde Lentinula edodes ekstraktının ishal ve deri döküntüsü gibi hafif yan etkilere yol açtığı, 1 haftaboyunca 50 mg/gün büyük dozlarda bile akut toksik olduğuna dair hiçbir kanıt bulunmamıştır. Sonuç olarak çalışmamızda shiitakemantarı uygulanan dozlarda sıçan karaciğer dokusuna gerek apoptotik belirteçlerin ekspresyonu bakımından gerekse histopatolojikolarak zararlı etki göstermemiştir.Öğe Melatonin ameliorates cardiac remodelling in fructose?induced metabolic syndrome rat model by using genes encoding cardiac potassium ion channels(Springer, 2021) Ovalı, Mehmet Akif; Öztopuz, Özlem; Vardar, Selma ArzuBackground Metabolic syndrome comprises a group of disorders, including cardiac abnormalities. Ventricular arrhythmias observed in metabolic syndrome are due to the impaired ventricular repolarization. This study aims to determine the efects of melatonin on cardiac ventricular repolarization in metabolic syndrome rat model. Methods and results Sprague–Dawley rats were divided into control (n=8), melatonin (n=8), metabolic syndrome (n=8) and metabolic syndrome+melatonin (n=8) groups. Fructose (200 g/lt/day) was added into the drinking water during 8 weeks of rats to induce metabolic syndrome model. In the last two weeks, melatonin (20 mg/kg/day) was administered via oral gavage. Blood pressure measurements and ECG recordings were taken at three diferent times. Blood and left ventricular tissue samples were harvested and the KCNQ1,3 and KCNH2 gene expressions were analysed by qRT-PCR method. We observed insulin resistance, hyperglycemia, dyslipidemia and higher systolic blood pressure in metabolic syndrome group (p<0.01, for all). Prolonged QT interval was observed in metabolic syndrome group (p<0.001). The expression levels of the KCNQ genes encoding the Kv7 channel was signifcantly reduced, however KCNH2 gene which encodes Kv11.1 channel was increased in metabolic syndrome group compared to control group (p<0.05, p<0.001, respectively). Melatonin signifcantly normalised the prolongation on QT interval in metabolic syndrome group (p<0.001) and the expressions of the KCNQ (p<0.002) and KCNH2 genes (p=0.003). Conclusions The present study revealed that melatonin had ameliorative efects on ventricular repolarization by improving the prolonged QT duration in rats with metabolic syndrome and this efect was generated by the KCNQ and KCNH2 gene families.Öğe Possible protective activity of n?acetyl cysteine against cisplatin?induced hepatotoxicity in rats(Springer, 2021) Coşkun, Özlem; Öztopuz, Özlem; Büyük, BaşakCP is one of the most widely used antineoplastic agents. However, its clinical application is very limited due to its severe toxic efects. The present study aimed to reveal the efects of NAC, which exhibits broad biological activities in reducing CP-induced liver damage, in consideration of biochemical, genetic, and histopathological fndings. Twenty-eight wistar rats were randomly divided into four groups of seven animals. A dose of saline was administered (i.p.) to the control group for 5 days. One dose of NAC (200 mg/kg) was administered to the NAC group for 5 days (i.p.). To the NAC + CP group, a dose of CP (7.5 mg/kg) was administered on days 2 and 5 of the experiment, a dose of NAC (200 mg/ kg) (i.p.) was administered for 5 day of the experiment. CP (7.5 mg/kg) was administered to the CP group on days 2 and 5 of the experiment. At the end of the experiment, the biochemical, histological, and mRNA expression analyses of the liver tissues isolated from all the rats were performed. A statistically signifcant decrease was observed in the AST and ALT enzyme activities in Group NAC + CP compared to Control and CP groups. In addition, it was determined that the NAC administration reduced CPinduced infammation by increasing the level of NF-κB and decreased CP-caused oxidative stress by decreasing the GPx level. Moreover, the histopathological analyses showed that NAC improved liver morphology. It was revealed by Western blotting analysis that NAC promoted Bcl-2 signaling and decreased p53 signaling. The fndings herein showed that NAC could help alleviate hepatotoxicity, a serious therapeutic complication, by reducing CP-induced oxidative stress and playing an efective part in the regulation of apoptotic markers.Öğe The effect of medical ozone on oxidative stress and neuroinflammation in the early stage after experimental status epilepticus(Springer, 2021) Çokyaman, Turgay; Öztopuz, Özlem; Coşkun, Özlem; Büyük, Başak; Kiraz, Hasan Ali; Elmas, SaitPreservation of the brain is important to reducing recurrent seizures and other neurological sequelae after status epilepticus (SE). Medical ozone (MedO3) shows antioxidant, anti-inflammatory and anti-apoptotic properties in the human body. In this study, it was aimed to understand the neuroprotective potential of MedO3 in the acute period after SE. Mature rats of Wistar Albino were used for the study. Group design O3 + SE: SE induced after MedO3, O3: MedO3 alone was given, SE: SE only induced, SE + O3; MedO3 given after SE, C: control and S: sham control group. SE was induced with lithium-pilocarpine experimental model and evaluated on the Racine scale. Peripheral blood samples and brain tissue samples were taken before decapitation. Histopathological evaluation of the hippocampus of the rats given medical O3 before and after SE were studied. The highest peripheral blood oxidative stress index (OSI) was found in SE group. The OSI level in O3 + SE and SE + O3 was significantly higher than SE/C/S. Gene expressions of TNF-α and IL-1β mRNA were significantly higher in SE compared to other groups. Histopathologically; eosinophilia, cellular shrinkage and interstitial oedema were detected in the most severe SE and to a lesser extent in O3 + SE/ SE + O3. MedO3 reduced SE-induced oxidative damage, neuroinflammation and neuronal injury and contributed positively to neuroprotection.
