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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 Lysine-Based Two-Component Organogelator: Naproxen Carrier Soft Material(Wiley-V C H Verlag Gmbh, 2023) Colak, Mehmet; Kaya, Guelsen; Adnan Hayaloglu, Ali; Demirel, Nadir; Hosgoeren, HalilWe demonstrated that N epsilon -alkanoyl-L-lysine ethyl ester/N-alkanoyl-L-phenylalaninate gelling agents were constructed as a two-component gelling strategy and applied as drug carriers in friendly solvents commonly used. Our designs are expected to have an edge in contrast to the other lipid-based systems due to cheap raw materials, reducing the required amount of carrier, low molecular weight, ease of loading, simple dose adjustability, skin spreadability, and improved drug retention times. It could be loaded with Naproxen (Npx) with a high loading efficiency (up to 100 % as a percentage of gelator) without gel disruption. A complementary in vitro drug release study under specific pH was conducted and performed at different drug and gelator concentrations. These results reveal that the release of Npx from the supramolecular organogels was significantly retarded with increasing organogelator engagement from 0.46 % to 0.92 %, the initial release rate considerably reduced, from 18.75 % to 7.21 %, respectively; that is release rate shows a 2.6-fold decrease; this result showed that the gelator concentration could control drug release. whereas the increasing Npx concentration enhanced it. Altogether, this work produces valuable outcomes, which may be relevant to the pharmaceutical industry, suggesting that new platforms may deliver NSAID ( non-steroidal anti-inflammotory drug) molecules. The study showed controlled release of naproxen was achieved with high loading efficiency (up to 100 % in percent gelator) with different drug and gelator concentrations without damaging the gel structure.imageÖğe Protective effects of buloxibutid and empagliflozin on hypertension-induced cardiac and vascular injury in rats(Springer, 2026) Ozhan, Onural; Colak, Mehmet; Karaca, Elif; Dogru, Feyzi; Kucukakcali, Zeynep; Acet, Ahmet; Parlakpinar, HakanThis study aims to see the individual and combined effects of Angiotensin II type 2 (AT2) receptor agonist buloxibutid (also known as Compound 21 or C21) and sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin (EMPA) on effects of hypertension (HT), which is common today, on the heart, and vascular tissue. Male rats of the Sprague Dawley were divided into 5 groups: Control (C) group, HT group, HT + C21 group, HT + EMPA group and HT + C21 + EMPA group. After the protocol was completed, hemodynamic measurements were taken and heart and aorta tissues were evaluated biochemically, histopatologically and immunohistochemically. When the mean blood pressure (BP) values were compared, the mean BP of the HT group increased significantly compared to the C group (p < 0.05). Superoxide dismutase, glutathione and glutathione peroxidase activities in the heart, glutathione and catalase activities in the descending aorta were significantly higher in all treated groups compared to the HT group (p < 0.05). In the HT + C21 + EMPA group, histopathological damage score in hematoxylin-eosin (HE) stained heart sections compared to the HT group showed a decrease in tissue damage but cell infiltration was still observed. When HE staining method was applied, it was determined that the thoracic aorta sections in group C had normal histologic structure. In the HT group, dilatation in some parts and irregularities in elastic lamellae were observed. It was observed that the treated groups were similar to group C. When considering the individual and combined effects of C21 and EMPA, positive results on heart and vascular tissue were observed by hemodynamic, biochemical and histopathological analyses.Öğe Renoprotective effects of compound 21 and empagliflozin in L-Name-induced hypertensive rats(Bmc, 2025) Ozhan, Onural; Colak, Mehmet; Karaca, Elif; Dogru, Feyzi; Kucukakcali, Zeynep; Acet, Ahmet; Parlakpinar, HakanBackground This study investigated the renoprotective effects of compound 21 (C21) and empagliflozin (EMPA) individually and in combination in an N omega-Nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rat model. The objective of this study was to evaluate their impact on oxidative stress (OS), biochemical markers, and histopathological changes in renal tissues. Methods Male Sprague-Dawley rats were divided into five groups: control, hypertension (HT), HT + C21, HT + EMPA, and HT + C21 + EMPA. Hypertension was induced by intraperitoneal L-NAME administration. Biochemical analyses of kidney tissue and histopathological evaluations were conducted to assess the treatment effects. Results Both C21 and EMPA significantly reduced the levels of OS markers, such as malondialdehyde, while increasing the levels of antioxidants, such as total antioxidants and glutathione. Compared with the individual treatments, the combination of C21 and EMPA exhibited superior efficacy in mitigating OS by significantly increasing superoxide dismutase and glutathione peroxidase activities. Furthermore, these treatments alleviated histopathological damage, including glomerular collapse, tubular degeneration, and interstitial inflammation, which were prominent in the HT group. The combined therapy group presented nearly normal histological structures in kidney tissues, with reduced inflammation and cellular damage. Urinary biochemical markers also reflected improved renal function in the treated groups, particularly in the combined therapy group. These findings indicate that the synergistic effects of C21 and EMPA enhance their protective impact on renal tissues. Conclusion C21 and EMPA demonstrated significant renoprotective effects in this HT model by reducing OS, enhancing antioxidant defenses, and mitigating renal tissue damage. Their combined administration offered synergistic benefits, highlighting their potential as a therapeutic strategy for hypertension-induced renal injury. Further research is warranted to validate these findings in clinical settings.Öğe The effects of apocynin on ciprofloxacin-induced oxidative stress-related cardiotoxicity(Nature Portfolio, 2025) Ozhan, Onural; Colak, Mehmet; Yildiz, Azibe; Durhan, Merve; Vardi, Nigar; Cigremis, Yilmaz; Colak, CemilCiprofloxacin (CFX), a fluoroquinolone antibiotic, is known to induce oxidative stress-mediated cardiotoxicity. This study investigates the potential protective and therapeutic effects of apocynin (APO), a selective NADPH oxidase (NOX) inhibitor and potent antioxidant, against CFX-induced myocardial injury in rats. Thirty-two male Wistar albino rats were randomly divided into four groups (n = 8). CFX (25 mg/kg, i.p.) was administered twice daily for one week, while APO (20 mg/kg, i.p.) was given once daily for four days either before or after CFX treatment. Hemodynamic parameters (heart rate, systolic, diastolic, and mean blood pressures) and electrocardiographic (ECG) indices (PR, QRS, and QT intervals) were recorded invasively. Histopathological evaluations assessed myocardial inflammation, cardiomyocyte degeneration, and aortic intima-media thickness. Biochemical analyses of cardiac and aortic tissues included measurements of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels. CFX administration significantly elevated cardiac MDA by similar to 45% and decreased SOD and CAT activities by similar to 30-35% (p < 0.05) compared with controls. These alterations were markedly attenuated in APO-treated rats, where antioxidant enzyme activities increased by similar to 25-40% and MDA levels were restored toward normal values (p < 0.05 vs. CFX). APO also shortened the QT interval by similar to 15% and improved systolic pressure by similar to 12% compared with the CFX group (p < 0.05). Histopathological findings confirmed reduced myocardial degeneration and inflammatory infiltration in both APO + CFX and CFX + APO groups. APO effectively ameliorated CFX-induced cardiac oxidative injury by inhibiting NOX2-mediated reactive oxygen species formation and restoring antioxidant defense mechanisms, leading to functional improvement in ECG and hemodynamic parameters. These results suggest that targeted NOX inhibition may represent a practical pharmacological approach to reduce fluoroquinolone-associated cardiotoxicity, warranting further translational investigation.
