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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 Ahmet
The 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.
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, Cemil
Panax 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.
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, Hakan
Aim: 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.
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, Hakan
Doxorubicin (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.
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, Engin
Three 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.
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, Yusuf
Abstract: 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 treatment
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, Onural
Biocompatible 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.
Cardiovascular effects of panax ginseng
(2016) Ozhan, Onural; Acet, Hacı Ahmet; Ermiş, Necip; Parlakpınar, Hakan
Dünyada 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 amaçladık
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, Fatih
Background 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.
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, Mahmut
Background 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.
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, Ahmet
Myocardial 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.
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, Hakan
Introduction 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.
Does apocynin increase liver regeneration in the partial hepatectomy model?
(Tubitak Scientific & Technological Research Council Turkey, 2023) Bilgic, Yilmaz; Kanat, Burhan Hakan; Ozhan, Onural; Yildiz, Azibe; Aksungur, Zeynep; Erdemli, Mehmet Erman; Vardi, Nigar
Background/aim: Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats.Materials and methods: A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. Results: In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). Conclusion: Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.
Dose-dependent subacute cardiovascular effects of modafinil in rats
(Taylor & Francis Ltd, 2022) Canyurt, Dilan; Tanriverdi, Lokman Hekim; Ozhan, Onural; Cansel, Mehmet; Parlakpinar, Hakan; Vardi, Nigar; Cigremis, Yilmaz
Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.
Efeito da genisteina na ototoxicidade induzida pela cisplatina e estresse oxidativo
(Assoc Brasileira Otorrinolaringologia & Cirurgia Cervicofacial, 2022) Tan, Mehmet; Toplu, Yuksel; Varan, Emrah; Sapmaz, Emrah; Ozhan, Onural; Parlakpinar, Hakan; Polat, Alaadin
Objetivo: A cisplatina e um agente antineoplasico usado em adultos e criancas para o tra-tamento de diversas lesoes malignas. Pode causar ototoxicidade irreversivel. A genisteina e um fitoestrogeno que funciona como antioxidante e inibidor do ciclo celular ao inibir as enzi-mas DNA topoisomerase e tirosina-quinase. O efeito protetor da genisteina na prevencao da ototoxicidade induzida pela cisplatina e os niveis de estresse oxidativo foram investigados. Metodo: Trinta e dois ratos Sprague Dawley foram usados em 4 grupos (controle, cisplatina, cis-platina + genisteina, genisteina). As medidas das emissoes otoacusticas por produto de distorcao foram tomadas nos dias 1, 2 e 5 do protocolo do teste. Foram medidos os niveis sericos de malondialdeido, superoxido dismutase, catalase, glutationa peroxidase, estado antioxidante total, estado oxidante total e indice de estresse oxidativo. Resultados: A audicao do grupo cisplatina + genisteina foi melhor do que a do grupo cisplatina. Enquanto os parametros malondialdeido, estado oxidante total e indice de estresse oxidativo diminuiram significantemente no grupo cisplatina + genisteina em comparacao com o grupo cisplatina, o superoxido dismutase mostrou aumento significantemente (p < 0,05). Conclusao: A genisteina apresentou efeitos positivos contra a ototoxicidade com seu efeito antioxidante. Nivel de evidencia: Nivel 3. (c) 2021 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Publicado por Elsevier Editora Ltda. Este e um artigo Open Access sob uma licenca CC BY (http:// creativecommons.org/licenses/by/4.0/).
The Effect of Ebselen on Motor Performance, Balance Skills and Analgesia in A Rat Model of Parkinson's Disease
(Karger, 2021) Parlakpinar, Hakan; Arslan, Fatma Dilan; Ozhan, Onural; Vardi, Nigar
[Abstract Not Available]
Effect of Melatonin on Increasing the Effectiveness of Liver Preservation Solution
(Aves, 2023) Erdogan, Mehmet Mustafa; Erdemli, Mehmet Erman; Ozhan, Onural; Erdemli, Zeynep; Bag, Harika Gozde Gozukara; Vardi, Nigar
Background/Aims: Various tissue preservation solutions are used during the removal of the organ and during transplantation to protect the normal histological and biochemical characteristics of tissue while performing a successful liver transplant. In our study, it was aimed to investigate the effects of intraperitoneal melatonin administration on liver preservation damage before transplantation. Materials and Methods: In our study, the histological and biochemical characteristics of University of Wisconsin + melatonin group rats treated with melatonin 45 minutes before hepatectomy were compared between serum physiologic group and University of Wisconsin group. Results: When hematoxylin and eosin staining was evaluated in terms of hydropic degeneration, sinusoidal dilatation, and hepatocyte necrosis, there was no statistically significant difference. Caspase 3 immunohistochemical staining showed a significant increase in Caspase 3 immunoreactivity positivity at the 12th-hour University of Wisconsin group compared to University of Wisconsin + melatonin group. As a result of biochemical analysis, the malondialdehyde and total oxidant status levels in the University of Wisconsin + melatonin group decreased significantly compared to the University of Wisconsin group. When the reduced glutathione activity and total antioxidant capacity level were compared, a significant increase was observed in the University of Wisconsin + melatonin group compared to the University of Wisconsin group at the 12(th) hour. It was also found that aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels decreased significantly in the University of Wisconsin + melatonin 12(th)-hour group compared to the University of Wisconsin 12(th) hour and control group. Conclusion: When the findings were evaluated, intraperitoneal administration of melatonin, a cytoprotective antioxidant, was found to play an effective role in preserving immunohistochemical and biochemical properties of liver tissue integrity and hepatocytes in University of Wisconsin solution.
Effects of antiepileptic drugs on ovaries of female Wistar rats
(Taylor & Francis Ltd, 2022) Osmanlioglu, Seyma; Yildiz, Azibe; Vardi, Nigar; Karaaslan, Merve; Ozhan, Onural; Parlakpinar, Hakan
Valproate (VPA) induced changes in ovarian morphology are observed in humans with epilepsy and in non-epileptic animals. The effects of lamotrigine (LTG) on female reproduction is not well known. We investigated whether LTG might be a safer drug for use with patients of reproductive age. Forty Wistar albino female rats were divided into five groups. The control group was injected with saline-vehicle solution. The low dose (LD)-VPA group was injected with 100 mg/kg VPA. The high dose (HD)-VPA group was injected with 500 mg/kg VPA. The LD-LTG group was injected with 10 mg/kg LTG. The HD-LTG group was injected with 50 mg/kg LTG. We evaluated histological and biochemical changes in the ovaries. The number of atretic and cystic follicles was increased in the HD-VPA and HD-LTG groups compared to the control group. A significant increase in malondialdehyde level was found in the VPA groups compared to the control and LTG groups. No significant differences in total glutathione levels or superoxide dismutase activity were found among study groups. Catalase activity was significantly higher in HD-VPA and HD-LTG groups compared to the control, LD-VPA and LD-LTG groups. Prevalence and intensity of caspase-3 immunoreactivity in the luteal cells were significantly greater in the HD-LTG group compared to the control group. VPA administration caused polycystic ovarian syndrome-like changes in the ovary. We found that LD-LTG, which reflects the dose for humans, might be a safer option for use during the reproductive age.
Effects of apocynin on sciatic nerve injury in rabbits
(Taylor & Francis Ltd, 2023) Durak, Mehmet Akif; Ozhan, Onural; Tetik, Bora; Yildiz, Azibe; Aksungur, Zeynep; Vardi, Nigar; Turkoz, Yusuf
We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.
Effects of drugs commonly used in Sars-CoV-2 infection on renal tissue in rats
(2023) Yıldız, Azibe; Ozhan, Onural; Vardi, Nigar; Akyuz, Mustafa; Bakar, Busra; Ulu, Ahmet; Taslıdere, Elif
Aim: In December 2019, the coronavirus disease was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some drugs were repurposed for this disease treatment. Hydroxychloroquine (HCQ), favipiravir (FAV), molnupiravir (MOL), and dexamethasone (DEX) were widely used for the treatment of the disease. To increase the success of the treatment of coronavirus disease, there was used some of these drugs in combination. On the other hand, limited studies report these drugs’ side effects. Therefore, this study was designed to evaluate the possible effects of these drugs and their combinations on the kidney tissues of rats without viral load. Materials and Methods: Male Wistar albino rats were divided into control, HCQ, FAV, HCQ+FAV, HCQ+FAV+DEX, MOL, and MOL+DEX groups. At the end of the experiment, the serum kidney tissue samples were taken. Serum samples were analyzed for urea and creatinine. Kidney tissue samples were assessed as histopathological and immunohistochemical for heat shock protein 60 (HSP60), caspase-3, and receptor-interacting protein kinase-3 (RIPK3). Results: Urea and creatinine levels were within the normal range in all groups. Histopathologically, all drugs and their combinations caused tubular degeneration. On the other hand, histopathological alterations were more prominent in the HCQ group. The oxidative stress marker HSP60 was significantly increased in FAV, MOL, and MOL+DEX groups, while it was similar to the control group in the HCQ groups. Apoptosis marker caspase-3 expression was found to be prominently higher in other drug groups except the FAV group. Expression of RIPK3, a marker of necroptosis, was significantly increased in all drug groups. Conclusion: Taken together, the data of our study show that the administration of all drugs alone and in combination may cause structural damage to the kidney. Furthermore, our results indicate that HCQ can exhibit more damaging effects compared to other drugs.

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