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Öğe Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II-induced hypertension(Wiley, 2023) Tanriverdi, Lokman Hekim; Ozhan, Onural; Ulu, Ahmet; Yildiz, Azibe; Ates, Burhan; Vardi, Nigar; Acet, Haci AhmetThe MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin-angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II-induced hypertension in rats. Sprague Dawley rats were subject to 4-week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 mu g/kg), AVE0991 (576 mu g/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail-cuff plethysmography at 1, 15, and 29 days post-treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin-A (CYP-A), monocyte chemoattractant protein-1 (MCP-1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase-2 and -9, NADPH oxidase-4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP-1 and CYP-A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin-converting enzyme-2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II-induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.Öğe Acute and subacute cardiovascular effects of synthetic cannabinoid JWH-018 in rat(Springer, 2025) Ozhan, Onural; Ermis, Necip; Celbis, Osman; Samdanci, Emine; Petekkaya, Semih; Oruc, Mucahit; Soylu, OzcanPurposeThis study investigates the cardiovascular effects of the synthetic cannabinoid naphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-018) in rats. The research aims to evaluate the pharmacologic, cardiologic, biochemical, and histopathological effects of acute and subacute administration at low and high doses. The primary research question is how JWH-018 impacts heart function, blood pressure, ECG patterns, and cardiac tissue integrity.MethodsWistar albino rats were divided into five groups: control, acute low-dose (ALD, 0.5 mg/kg), acute high-dose (AHD, 5 mg/kg), subacute low-dose (SALD, 0.5 mg/kg for 14 days), and subacute high-dose (SAHD, 5 mg/kg for 14 days). Cardiovascular effects were assessed using echocardiography, hemodynamic and ECG analysis, histopathology, biochemical markers, and LC-MS/MS quantification of JWH-018 and its metabolites in heart tissue.ResultsAcute high-dose JWH-018 caused bradycardia and hypotension, while subacute high-dose increased heart rate but continued to lower blood pressure. JWH-018 induced cardiac arrhythmias, conduction blocks, and ischemic ECG changes, with prolonged QT intervals in subacute high-dose rats. Histopathological findings revealed myocardial infarction-like features, including contraction bands and ischemic damage, particularly in subacute groups. Elevated pro-BNP and triglycerides indicated cardiac stress and metabolic effects. JWH-018 and its metabolites were detected in heart tissue, primarily in high-dose groups.ConclusionsJWH-018 has significant cardiovascular risks, causing heart rate dysregulation, hypotension, arrhythmias, and ischemic damage. These effects depend on dose and duration. The study highlights the potential dangers of synthetic cannabinoids, emphasizing that they should not be considered safe alternatives to natural cannabis.Öğe Acute and Subacute Effects of Low Versus High Doses of Standardized Panax ginseng Extract on the Heart: An Experimental Study(Humana Press Inc, 2019) Parlakpinar, Hakan; Ozhan, Onural; Ermis, Necip; Vardi, Nigar; Cigremis, Yilmaz; Tanriverdi, Lokman H.; Colak, CemilPanax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.Öğe Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin(Wiley, 2024) Ayik, Seyhan; Gunata, Mehmet; Ozhan, Onural; Yildiz, Azibe; Vardi, Nigar; Sonmez, Emre; Ermis, NecipBackgroundDespite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor.ObjectivesWe aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH.MethodsThe rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 mu g/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed.ResultsMonotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and alpha-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and alpha-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it.ConclusionALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.Öğe Alamandine: Protective Effects Against Renal Ischemia-Reperfusion Injury-Induced Renal and Liver Damage in Diabetic Rats(Wiley, 2025) Cengiz, Ayse Nuransoy; Ozhan, Onural; Tanriverdi, Lokman Hekim; Dogru, Feyzi; Yildiz, Azibe; Polat, Alaadin; Vardi, NigarAlamandine (ALA) is a heptapeptide discovered in 2013 within the renin-angiotensin system (RAS). Given the high prevalence of diabetes mellitus (DM) in society and its comorbidities, especially renal failure, which significantly impairs the quality of life, this study aimed to investigate the protective effects of ALA against renal ischemia-reperfusion (I/R) injury in diabetic rats. Our aim was to develop preventive therapies for DM and diabetic renal failure. Forty-eight 3-month-old male Sprague-Dawley rats were induced by administering a single intraperitoneal dose of 50 mg/kg of streptozotocin (STZ). Rats were divided into four groups. Right nephrectomy was performed through dorsolateral incisions in all rats, followed by occlusion of the left renal vessels for 1 h to induce ischemia. Reperfusion of the left kidney was initiated by removing the clamp and allowing 24 h of reperfusion. Histopathological examination of the kidney tissues revealed necrotic changes and tubular dilatation in the I/R group, which were significantly reduced in the ALA + I/R group. Immunohistochemical analysis showed increased immunoreactivity for interleukin-6 (IL-6) and caspase-3 in the I/R group, whereas the ALA + I/R group demonstrated significantly lower immunoreactivity for these markers. Liver histology showed irregular hepatocyte cords and sinusoidal dilatation in the I/R group, whereas the ALA + I/R group exhibited a preserved classical lobular structure with reduced histopathological changes. Blood parameters, serum biochemistry, and tissue findings were also analyzed. Our study demonstrated the protective effects of ALA on renal and liver tissues against damage induced by renal I/R injury in a diabetic background. Moreover, ALA exhibited protective effects against liver damage resulting from renal I/R injury.Öğe Ameliorating effects of low-dose ketamine administrations on opioid-induced memory impairments and neurodegeneration in mice(2023) Uyar, Emre; Seker, Ugur; Ozhan, Onural; Acıkgul, Muhammet Burak; Colak, Mehmet; Izcı, Sevde Feyza; Parlakpınar, HakanAim: Opioids have indispensable roles in pain management. A strong link exists between opioid use and memory impairments, mainly with continuous use. This study investigated the effects of two opioid drugs, meperidine and fentanyl, on emotional memory functions, brain morphology, and the possible protective effects of low-dose ketamine in mice. Materials and Methods: A passive avoidance (PA) test was used to measure emotional memory functions following seven daily drug applications in 48 male Balb/C mice (30-35 g). Meperidine (10 mg/kg), fentanyl (0.3 mg/kg), ketamine (5 mg/kg), and combinations of ketamine with the opioids were intraperitoneally injected daily. No drugs were utilized during the testing days. Brain tissues were obtained after sacrification and put into diluted formalin solution for histopathological analysis. Results: Transfer latencies of the meperidine and fentanyl-treated groups in the PA test were lower than in the vehicle-treated group (p<0.01, p<0.05, respectively). Ketamine combined with meperidine had higher latencies than in the meperidine-treated group (p<0.05). The augmenting effects of ketamine were evident against fentanyl and meperidine-induced neurotoxicity as morphologic alterations were reduced. Conclusion: Low-dose ketamine may fend against opioid-induced neurotoxicity and emotional memory impairments, especially against meperidine, which can be a practical alternative to fentanyl in clinical settings.Öğe Ameliorative effects of humic acid on copper-induced liver injury via antioxidant and chelating mechanisms(2025) Cagin, Yasir Furkan; Doğru, Feyzi; Erdogan, Mehmet Ali; Atayan, Yahya; Berber, Ilhami; Yıldız, Azibe; Ozhan, OnuralThe liver plays a critical role in metabolism, detoxification, and maintaining internal homeostasis. Excessive accumulation of copper (Cu), a metal with known toxic effects, can cause severe hepatic injury, particularly in genetic disorders such as Wilson’s disease. This study aimed to investigate the chelating and antioxidant properties of humic acid (HA) in mitigating Cu-induced toxicity, oxidative damage, and apoptosis in an experimental model. Forty male rats were randomly assigned to four groups (n=10). Group I received a standard diet (Control); Group II received HA, 536 mg/kg/day, oral); Group III was administered copper sulfate (CuSO₄, 75 mg/kg/day, oral); Group IV received both HA and CuSO₄ for 14 days. Blood and liver tissue samples were collected post-euthanasia for biochemical, histopathological, and immunohistochemical analyses. Biochemical parameters included alanine aminotransferase (ALT), aspartate aminotransferase (AST), copper (Cu), ceruloplasmin, malondialdehyde (MDA), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Caspase-3 and 9 expressions were evaluated immunohistochemically. The CuSO₄ group showed significantly increased ALT, AST, and Cu levels, alongside elevated MDA and TOS, and reduced TAS, GSH, SOD, CAT, and GPx levels (p<0.05). HA treatment significantly reversed these alterations. Histopathologically, severe hepatic damage induced by CuSO₄ was markedly alleviated by HA. Additionally, caspase-3 and 9 expressions were significantly upregulated in the CuSO₄ group but notably reduced with HA administration. Humic acid exhibits both chelating and antioxidant effects in alleviating copper-induced hepatotoxicity. It reduces hepatic Cu accumulation, mitigates oxidative stress and apoptosis, and alleviates liver damage. Further clinical studies are required to determine its optimal dosage, formulation, and safety for human use.Öğe Angiotensin II type 2 receptor agonist treatment of doxorubicin induced heart failure(Taylor & Francis Ltd, 2023) Ermis, Necip; Ulutas, Zeynep; Ozhan, Onural; Yildiz, Azibe; Vardi, Nigar; Colak, Cemil; Parlakpinar, HakanDoxorubicin (DOX) is an anthracycline derivative used for treatment of malignancies; however, its clinical use is limited by its cardiotoxicity. We investigated the effects of angiotensin II type 2 receptor agonist compound 21 (C21) on DOX induced heart failure in rat heart. We compared C21 with losartan (LOS), an AT 1 receptor antagonist used for treating heart failure. We allocated 40 rats into five groups of eight: saline treated control group, DOX group administered a single 20 mg/kg dose of DOX, DOX + C21 group administered 0.3 mg/kg C21 for 21 days following the 20 mg/kg dose of DOX, DOX + losartan (LOS) group administered a 21 day regimen of 20 mg/kg LOS following the single dose of DOX, and a DOX + LOS + C21 group administered 0.3 mg/kg C21 and 20 mg/kg LOS for 21 days following the single dose of DOX. We assessed histopathology and conducted echocardiograpic and hemodynamic measurements. Left ventricular ejection fraction (EF) was reduced only in the DOX treated group. C21, LOS and C21 + LOS therapy prevented decreased EF due to DOX. Less histopathology was observed in the DOX + LOS + C21 group than for the other treatment groups. Application of C21 decreased DOX induced cardiac injury similar to LOS. Combined use of C21 and LOS was most beneficial for DOX induced heart failure.Öğe Antioxidant and Antimicrobial Activities, and Phenolic Compounds of Selected Inula species from Turkey(Sage Publications Inc, 2013) Gokbulut, Alper; Ozhan, Onural; Satilmis, Basri; Batcioglu, Kadir; Gunal, Selami; Sarer, EnginThree Inula species, I. viscosa, I. helenium ssp. turcoracemosa and I. montbretiana, collected from different locations of Anatolia were investigated for their antioxidant and antimicrobial potential, and their total phenolic content and phenolic composition. Antioxidant activities of various extracts of the plant parts were measured using DPPH radical scavenging and ABTS assays. Antimicrobial potential of methanol extracts of the plant parts was determined by the agar dilution method against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Candida tropicalis. All the extracts were more active against Gram-positive bacteria and yeasts than Gram-negative bacteria. The extracts exhibited antioxidant and antimicrobial activities in different concentrations. Total phenolic concentration of the extracts was estimated with Folin-Ciocalteu reagent using gallic acid as standard. The total phenolic content varied widely in different parts of the three tested Inula species, ranging from 21.1 +/- 0.8 to 190.9 +/- 6.1 mg GAE/g extract. Phenolic components, such as chlorogenic acid, caffeic acid, rutin, myricetin, quercetin, luteolin and kaempferol were quantified by HPLC-DAD in the methanol extracts of the Inula species. It was obvious that the antioxidant and antimicrobial properties of the plants were due to the phenolics.Öğe Arginine, symmetric and asymmetric dimethylarginine levels in the molsidomine treatment of experimental ischemia-reperfusion retinopathy(2019) Polat, Nihat; Atabey Ozer, Murat; Parlakpinar, Hakan; Aksungur, Zeynep; Ozhan, Onural; Turkoz, YusufAbstract: This study aimed to evaluate the mean changes in Arginine, Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA) levels in the ischemia/reperfusion (I/R) retinopathy and efficacy of treatment with molsidomine by these levels. Experiments were performed on the New Zealand white rabbits each weighing approximately 2.5 kg. 28 rabbits were assigned to the following 4 groups, group 1 consisted sham, group 2 consisted I/R, group 3 consisted I/R+ treatment with molsidomine, group 4 consisted prophylaxis with molsidomine +I/R. In the group 2, 3 and 4, ischemia was induced by raising the intraocular pressure to 150 mmHg for 60 minutes. After 60 min, the IOP was returned to normal pressure. 4 mg/kg/day molsidomine was administered intraperitoneally four days after I/R in group 3, one day before I/R and three days after I/R in group 4. Arginine, ADMA and SDMA levels were measured on the aqueous humor. The mean arginine levels were 12.3±4.8 ?mol/L in group 1, 12.4±1.4 ?mol/L in group 2, 13.2±2.4 ?mol/L in group 3 and 13.7±4.3 ?mol/L in group 4. No difference was present between the groups (p=0.807). The mean ADMA levels were 2.6±0.8 ?mol/L, 7.3±2.7 ?mol/L, 0.5±0.5 ?mol/L and 2.5±1.0 ?mol/L respectively. Significant increase was present in the group 2 and significant decrease was present in the group 3 (p=0.001). The mean SDMA levels were 1.0±0.3 ?mol/L, 1.8±0.2 ?mol/L, 0.3±0.3 ?mol/L and 1.0±0.4 ?mol/L respectively. Significant increase was present in the group 2 and significant decrease was present in the group 3 (p=0.001). L-Arginine levels were kept steady, ADMA and SDMA values decreased with molsidomine. Four days treatment with molsidomine after I/R may be beneficial more than prophylaxis and three days treatmentÖğe Biomimetic approach to tunable adhesion of polyurethane adhesives through Fe3+ crosslinking and hydrophobic tween units with balance of adhesion/cohesion forces(Elsevier Sci Ltd, 2019) Ates, Burhan; Koytepe, Suleyman; Balcioglu, Sevgi; Karaaslan, Merve Goksin; Kelestemur, Unzile; Gulgen, Selam; Ozhan, OnuralBiocompatible adhesives have some limitations such as weak adhesion and low flexibility. To overcome these limitations, we described multiple strategies to provide strong adhesion and high flexibility through Tweens, chlorogenic acid (CLA) and polyethylene glycol (PEG) by reducing excessive interaction between tissue and the adhesive. We synthesized polyurethane-based adhesives using aliphatic 4,4'-methylenebis(cyclohexyl isocyanate) (HMDI), PEG, CLA and Tween units. Hydrophobic side chains in polymer resulted in lower Tg (- 36.95-30.36 degrees C) which indicated more flexibility. The highest adhesion strengths were found as almost 346 kPa for bare polyurethane and 492 kPa for chelated polymer (PU-T40-CLA-15% (5% Tween 40, 15% chlorogenic acid and 80% PEG 200 containing polymer)) with FeCl3. The addition of Tween units provided more stable structure to polymers which proved with in vitro erosion studies. Relatively low erosion values were seen as 5.7, 5.6 and 8.2% in PU-T40-CLA-5% (15% Tween 40, 5% chlorogenic acid and 80% PEG 200 containing polymer), PU-T40-CLA-10% (10% Tween 40, 10% chlorogenic acid and 80% PEG 200 containing polymer), and PU-T40-CLA-15% (5% Tween 40, 15% chlorogenic acid and 80% PEG 200 containing polymer), respectively. In vitro biocompatibility results showed high cell viability in PU-T40-15% as more than 100%. Overall, our findings indicated that these material designs (PU-T-CLAs) provided to overcome the significant challenges of tissue adhesives by improving the flexible character and adhesive strength of the adhesives.Öğe Cardiovascular effects of panax ginseng(2016) Ozhan, Onural; Acet, Hacı Ahmet; Ermiş, Necip; Parlakpınar, HakanDünyada farklı ırk, yaş ve cinsiyetten yaklaşık 400 milyon insanda görülen kardiyovasküler hastalıklar (KVH), Dünya Sağlık Örgütü'nün "Bulaşıcı Olmayan Hastalıklar 2013-2020 Eylem Planı" içerisinde yer alan önemli bir hastalık grubudur. KVH' nın neden olduğu ölümler dünyada ve ülkemizde ilk sıradadır.Ülkemizde "Ginseng" olarak bilinen Panax ginsengbitkisinin kökleri yorgunluk, bitkinlik, konsantrasyon kaybı gibi durumlarda, iyileşme dönemlerinde mental ve fiziksel kapasitenin artırılmasında, anti-stres etki ile adaptojen olarak davranıp vücutta stresin oluşturduğu dejeneratif etkilerin azaltılmasında, diyabetik hastalarda kan şekerinin düzenlenmesinde, erektil disfonksiyonlu olgularda ereksiyon kapasitesinin ve libidonun artırılmasında tıbbi olarak kullanılmaktadır. Ayrıca hipertansiyon, hiperkolestrolemi ve oksidatif hasar gibi kardiyovasküler risk faktörleri bulunan bireyler arasında Ginseng'in gıda takviyesi olarak kullanımı gün geçtikçe artmaktadır. Literatürde Panax ginseng'in kardiyovasküler sistem üzerindeki farmakolojik etkinliğiyle ilgili tartışmalı veriler mevcuttur. Ginseng'in nitrik oksit sentezini artırarak hem hipertansif hem de hipotansif etki gösterdiği gözlenmiştir. Ginseng içeren gıda takviyelerinin otonom sinir sistemini etkileyerek kalp hızını azalttığı belirtilirken; aynı zamanda kan basıncını artırdığı, azalttığı veya kan basıncında herhangi bir değişiklik yapmadığı yönünde tartışmalı bulgular elde edilmiştir. Bu çelişkili verilerden, kan basıncını önce azaltıp daha sonra artırarak bifazik aktivite gösteren ginsenozitlerin sorumlu olduğu düşünülmektedir. Ayrıca akut ve kronik Ginseng kullanımına bağlı olarak çeşitli farmakolojik aktivite farklılıkları olduğu gözlenmiştir.Bu yazıda Ginseng'in kardiyovasküler etkilerini sunmayı amaçladıkÖğe Cardiovascular impact of consumption of sulfured-dried Malatya apricots (Prunus armeniaca L.) at varying SO2 levels: A comprehensive assessment in a rat model(Pergamon-Elsevier Science Ltd, 2025) Ayik, Seyhan; Yildiz, Azibe; Ozhan, Onural; Karaca, Yucel; Taslidere, Elif; Ermis, Necip; Vardi, NigarApricots known as sulfured-dried are those dried under the sun with sulfur dioxide (SO2), which extends their shelf life. Although sun-dried apricots are renowned for their cardiovascular benefits, the cardiovascular effects of sulfured-dried apricots (SDAs) remain poorly understood. To address this knowledge gap, we designed the present study to investigate the cardiovascular effects of consuming SDAs at varying SO2 levels in a rat model. The rats were randomly assigned to 6 groups. The Control group received standard rat chow, while the other 5 groups were fed a diet containing 10 % SDAs with differing SO2 concentrations (1500 ppm, 2000 ppm, 2500 ppm, 3000 ppm, and 3500 ppm) for 24 weeks. After echocardiography and hemodynamic assessment, cardiac histopathology and serum biochemistry were evaluated. Our findings indicate that an SDA diet containing 3500 ppm SO2 leads to myocardial damage and subsequent cardiac dysfunction, likely through TNF-alpha-mediated inflammation and apoptosis. In contrast, diets containing SDAs with SO2 levels between 1500 and 2500 ppm appeared to pose minimal cardiovascular risk. Because in these groups, there was no evidence of myocardial damage, cardiac inflammation, apoptotic cell death, or cellular stress in the cardiac myocytes. Also, these groups showed normal cardiac function in echocardiographic assessments. These results suggest that consuming SDAs with SO2 concentrations up to 2500 ppm SO2 may be safe for cardiovascular health.Öğe Changes in Melatonin, Cortisol, and Body Temperature, and the Relationship Between Endogenous Melatonin Levels and Analgesia Consumption in Patients Undergoing Bariatric Surgery(Springer, 2018) Altunkaya, Neslihan; Erdogan, Mehmet Ali; Ozgul, Ulku; Sanli, Mukadder; Ucar, Muharrem; Ozhan, Onural; Sumer, FatihBackground Melatonin has analgesic, anti-inflammatory, sedative, and anxiolytic properties. However, the relationship between endogenous melatonin levels and postoperative analgesic requirements has not been well elucidated in patients undergoing bariatric surgery. We studied endogenous melatonin levels, cortisol levels, body temperatures, and the relationship between the level of endogenous melatonin and postoperative morphine consumption. Methods The trial was conducted among 30 patients who were scheduled for laparoscopic bariatric surgery. Their ages were between 18 and 65 years and their BMIs were above 40 kg/m(2). Secretion of melatonin, cortisol, and body temperature was monitored before the anesthetic induction, at 2 h intraoperatively, and at 2, 6, 10, (2:00 A.M.) and 24 h postoperatively. For each patient, morphine consumption was assessed at postoperative visits. The primary outcomes were to measure endogenous melatonin levels and to examine the relationship between these levels and morphine consumption. The secondary outcome was to observe the changes in cortisol and body temperature. Results There was a significant decrease in melatonin levels when preoperative melatonin levels were compared with intraoperative and all postoperative follow-up periods (p < 0.05). When the correlation between plasma melatonin levels and the postoperative morphine consumption of the patients was inspected, there was a significant correlation in all of the follow-up periods (p < 0.05). When preoperative cortisol levels were compared with intraoperative and postoperative cortisol levels, there was a significant difference in the follow-up periods, except two periods (p < 0.05). Body temperatures were similar in all measurement periods. Conclusions Endogenous melatonin secretion was significantly decreased in the intraoperative and postoperative periods. Furthermore, there was a significant inverse correlation between changes in endogenous melatonin levels and morphine consumption.Öğe Changes in melatonin, cortisol, and body temperature, and the relationship between endogenousmelatonin levels and analgesia consumption in patients undergoing bariatric surgery(Sprınger, 233 sprıng st, new york, ny 10013 usa, 2018) Altunkaya, Neslihan; Erdogan, Mehmet Ali; Ozgul, Ulku; Sanli, Mukadder; Ucar, Muharrem; Ozhan, Onural; Sumer, Fatih; Erdogan, Selim; Colak, Cemil; Durmus, MahmutBackground Melatonin has analgesic, anti-inflammatory, sedative, and anxiolytic properties. However, the relationship between endogenous melatonin levels and postoperative analgesic requirements has not been well elucidated in patients undergoing bariatric surgery. We studied endogenous melatonin levels, cortisol levels, body temperatures, and the relationship between the level of endogenous melatonin and postoperative morphine consumption. Methods The trial was conducted among 30 patients who were scheduled for laparoscopic bariatric surgery. Their ages were between 18 and 65 years and their BMIs were above 40 kg/m(2). Secretion of melatonin, cortisol, and body temperature was monitored before the anesthetic induction, at 2 h intraoperatively, and at 2, 6, 10, (2:00 A.M.) and 24 h postoperatively. For each patient, morphine consumption was assessed at postoperative visits. The primary outcomes were to measure endogenous melatonin levels and to examine the relationship between these levels and morphine consumption. The secondary outcome was to observe the changes in cortisol and body temperature. Results There was a significant decrease in melatonin levels when preoperative melatonin levels were compared with intraoperative and all postoperative follow-up periods (p < 0.05). When the correlation between plasma melatonin levels and the postoperative morphine consumption of the patients was inspected, there was a significant correlation in all of the follow-up periods (p < 0.05). When preoperative cortisol levels were compared with intraoperative and postoperative cortisol levels, there was a significant difference in the follow-up periods, except two periods (p < 0.05). Body temperatures were similar in all measurement periods. Conclusions Endogenous melatonin secretion was significantly decreased in the intraoperative and postoperative periods. Furthermore, there was a significant inverse correlation between changes in endogenous melatonin levels and morphine consumption.Öğe Comparison of cilomilast, tadalafil, and both drug combinations in the treatment of monocrotaline-induced pulmonary arterial hypertension in rats(Bmc, 2025) Ermis, Necip; Ozhan, Onural; Yildiz, Azibe; Ulutas, Zeynep; Parlakpinar, Hakan; Ulu, Ahmet; Ates, BurhanBackground Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction and inflammation. This study aimed to evaluate the effects of cilomilast (CIL), a phosphodiesterase-4 inhibitor, and tadalafil (TAD), a phosphodiesterase-5 inhibitor, on PAH induced by monocrotaline (MCT) in rats. Methods Forty Wistar albino rats were divided into five groups: control, MCT, MCT + CIL, MCT + TAD, and MCT + CIL + TAD. PAH was induced via MCT, and treatments were administered orally from days 21 to 35. Hemodynamic parameters, right ventricular pressure (RVP), echocardiographic findings, and histopathological lung and heart tissue changes were assessed. Nitric oxide (NO) levels in lung tissue were also measured. Results Tissue NO levels were significantly greater in the MCT + CIL + TAD group than in the MCT group (p = 0.01). The RVP was lower in the MCT + TAD and MCT + CIL + TAD groups than in the MCT group (p < 0.05) but not in the MCT + CIL group. Histopathologically, lung perivascular infiltration and pulmonary artery wall thickness were significantly reduced in the MCT + CIL + TAD group, indicating an anti-inflammatory effect. However, CIL alone did not significantly impact pulmonary artery thickening or RVP. Conclusion CIL alone had no significant effect on PAH progression, but its combination with TAD improved inflammation scores and NO levels. These findings suggest that targeting inflammation alongside vasodilation may offer therapeutic benefits in PAH. Further studies with different doses and PAH models are recommended.Öğe Comparison of the effects of losartan, captopril, angiotensin II type 2 receptor agonist compound 21, and MAS receptor agonist AVE 0991 on myocardial ischemia-reperfusion necrosis in rats(Wiley, 2021) Ozhan, Onural; Parlakpinar, Hakan; Acet, AhmetMyocardial ischemia may occur as a result of pathophysiological and therapeutical applications such as atherosclerosis, thromboembolism, percutaneous transluminal coronary angioplasty, coronary artery bypass, and transplantation. In this study, we aimed to compare the effects of angiotensin (Ang) II type 2 (AT(2)) selective receptor agonist Compound 21 (C21), MAS receptor agonist AVE 0991, Ang II type 1 (AT(1)) selective receptor blocker losartan, and Ang-converting enzyme inhibitor captopril on haemodynamic parameters and infarct size on myocardial ischemia/reperfusion (MI/R)-induced necrosis in rats. To induce necrosis in the heart of rats, reperfusion for 2 h following ischemia for 30 min to the descending branch of the left main coronary artery was achieved. C21 (0.03 mg/kg), AVE 0991 (576 mu g/kg), losartan (2 mg/kg), and captopril (3 mg/kg) were administered as an intravenous infusion at 10 min before and throughout the ischemia. Then, the infarct size and risk area were calculated from the heart. The percentage of myocardial infarct size to area at risk ratio (%IS/AR) of groups was Control (MI/R) group: 48.9 +/- 8.8%; C21 group: 31.1 +/- 7.8%; AVE 0991 group: 29.9 +/- 4.8%; C21 + AVE 0991 group: 28.2 +/- 3.3%; Losartan + AVE 0991 group: 30.8 +/- 5.8%; Captopril + AVE 0991 group: 31.7 +/- 7.7%. %IS/AR of the drug-treated groups decreased significantly when compared to the MI/R group (P < 0.05). Our results indicate that the importance of AT(1), AT(2), and MAS receptors in the MI/R injury. Inhibition of Ang II formation by captopril, blockade of AT(1)receptor with losartan, and stimulation of AT(2)receptor with C21 and MAS receptor with AVE 0991 showed beneficial effects by reducing infarct size.Öğe Cytoprotective effects of molsidomine against methotrexate-induced hepatotoxicity: an experimental rat study(Dove Medical Press Ltd, 2019) Samdanci, Emine Turkmen; Huz, Mustafa; Ozhan, Onural; Tanbek, Kevser; Pamukcu, Esra; Akatli, Ayse Nur; Parlakpinar, HakanIntroduction and aim: Methotrexate (Mtx) is an antineoplastic and immunosuppressive drug that may cause hepatotoxicity, whereas molsidomine (Mol) is a vasodilating and antioxidant agent. This study aimed to investigate the potential protective effects of Mol in Mtx-induced liver toxicity in rats. Materials and methods: Forty Wistar albino rats were equally divided into five groups: control, Mol, Mtx, Mol Mtx, and Mtx Mol. Following treatment, the animals were sacrificed, and liver tissue samples were histopathologically evaluated using Roening grading and Bcl-2 antibody staining. Tissue oxidants, antioxidants, and serum transaminases were measured and statistically compared across all groups. Results: No hepatic fibrosis or steatosis was observed in any of the groups. In the Mtx group, grade 2 liver injury and score 2 Bcl-2 antibody staining were observed; however, in the Mol-Mtx group, these were lower (grade 1, score 1). There were no statistically significant differences in serum transaminase levels among groups. Malondialdehyde levels were higher in all rats that received Mtx, but no differences in myeloperoxidase levels were observed among the groups. Levels of tissue antioxidants, including superoxide dismutase, glutathione (GSH) peroxidase (GSH-Px), and reduced GSH, were significantly higher in the Mol-treated and Mol pre-treated groups. Catalan (CAT) levels were elevated in all Mol-treated groups, but only in that group were CAT levels statistically significantly higher than in the control group. Conclusion: Our results suggest that some oxidant levels could increase following Mtx administration in the liver, possibly contributing to liver damage, whereas Mol could mitigate the histopathological and biochemical effects of hepatotoxicity. However, molecular studies are required to understand the exact mechanisms of these alterations.Öğe Development of lidocaine-containing modified pleural talc structures as antibacterial drug delivery systems to prevent pleural effusion or pneumothorax(Springer, 2025) Ozhan, Onural; Koytepe, Suleyman; Ates, Burhan; Acari, Idil Karaca; Gurses, Canbolat; Parlakpinar, HakanPleurodesis is a common practice to close the pleural space and to treat persistent pneumothorax to prevent recurrent pleural effusion. When the patient has pleurodesis, the pleural fluid is drained first and then talc is applied to the pleural space. The talc application process consists of directly depositing the talc structure with the appropriate particle size into the relevant space. Both the space is filled and the patient's lung movement comfort is provided during the breathing process due to the slippery effect of the talc structure. Otherwise, the patient experiences a very painful process during the breathing process. However, some important indications can be observed both during and after the talc deposition. At the beginning of these indications is the formation of infection and innovative practices are very significant in eliminating such an infection. In order to prevent infection during talc process, intensive antibiotic application is made before and after the application. In this study, more effective and innovative talc structures were developed and the talc structure was modified with a zwitter ionic polymeric coating to prevent infection. A surface modification was carried out by attaching 3-vinylpropyl-triethoxysilane binding agent on the appropriately sized talc structures. The functionalized talc structure was transformed into a surface that would work with the kill and release principle. The structure of 2-(tert-butylamino)ethyl methacrylate was modified for this process. A quaternary ammonium structure was formed on the talc surface thereby, bacteria will be killed and then, removed from the surface. In the research, local anesthesic agent lidocaine was also loaded to provide convenience to the patient. Structural characterizations of the obtained structures were performed by Fourier Transform Infrared Spectrophotometer (FTIR). Its thermal properties were determined by thermogravimetric analysis (TGA), differential thermal analysis (DTA) and differential scanning calorimetry (DSC) techniques. Moreover, the antibacterial properties of the obtained structures were examined.Öğe Dexpanthenol prevents ovarian ischemic damage via antioxidant mechanisms in rats(2023) Vardi, Nigar; Parlakpinar, Hakan; Aksungur, Zeynep; Coskun, Ebru Incı; Polat, Seyhan; Yıldız, Azibe; Ozhan, OnuralOvarian torsion is a gynecological emergency characterized by ovarian ischemic damage. This study aimed to investigate the possible protective effects of dexpanthenol (DEX)-an antioxidant molecule-against ovarian ischemic damage in rats. The rats were simple randomly grouped into (1) Sham group (n=8); (2) Ischemia (I) group (n=8) (2 hours of I in ovaries); (3) DEX+I group (n=8) (500 mg/kg DEX administration 30 minutes before 2 hours of I.) The removed ovaries were examined histopathologically and biochemically. In the DEX+I group, necrosis-pycnosis severity was significantly reduced compared to the I group; but congestion-hemorrhage severity was similar. In the I group, malondialdehyde (MDA) and total oxidant status (TOS) levels were slightly increased, and glutathione (GSH) levels were significantly decreased compared to the Sham group. In the DEX+I group, MDA and TOS levels were slightly reduced and GSH levels were slightly increased compared to the I group. DEX prevents ischemic damage in rat ovaries via an antioxidant effect. Further research is needed to support our findings.
