WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Metformin Attenuates PTZ-Induced Seizures and Cognitive Impairment and Is Associated with Altered NOS/NO Signaling: Combined in Vivo and in Silico Evidence(Taylor & Francis Ltd, 2026) Ciltas, Arzuhan Cetindag; Sahin, Bilal; Hacisuleyman, Levent; Çetindağ Çiltaş, ArzuhanBackground: Epilepsy remains a major neurological disorder with high rates of drug resistance and cognitive decline. Repurposing neuroprotective drugs offers a promising approach. Metformin, a widely used antidiabetic agent, has shown anticonvulsant effects, yet its impact on nitric oxide synthase (NOS) isoforms in distinct brain regions remains unclear. Methods: Adult male Wistar rats were allocated into control, pentylenetetrazole (PTZ), or metformin+PTZ groups. Metformin (200 mg/kg, i.p.) was administered for 7 days before induction of acute PTZ seizures (45 mg/kg, i.p.). Seizure severity and latency were assessed using Racine's scale, and cognition was evaluated by the passive avoidance test (PAT). Nitric oxide (NO) and the expression of its synthesizing enzymes, inducible (iNOS), neuronal (nNOS), and endothelial (eNOS), were quantified in the cortex and hippocampus via enzyme-linked immunosorbent assay (ELISA). In silico analyses included target prediction and molecular docking to assess metformin - NOS interactions. Results: Metformin significantly reduced seizure severity, prolonged latency to the first myoclonic jerk, and prevented PTZ-induced memory impairment (all p < 0.001). These behavioral effects were accompanied by reductions in cortical and hippocampal nNOS and iNOS expression, decreased cortical eNOS levels, and lower NO accumulation. TargetNet predicted NOS isoforms among potential metformin targets, and docking indicated moderate binding affinity (-5.2 to -5.9 kcal/mol). Conclusion: Metformin exerted seizure-suppressing and cognition-preserving effects in an acute PTZ model, associated with reductions in NOS isoform expression and NO levels, suggesting altered NOS/NO signaling and supporting its potential as an adjunctive candidate for mitigating seizure-related neuronal dysfunction.Article Citation - WoS: 1Histological and Biochemical Effects of an Ethanolic Extract of <i>myrtus Communis</I> Leaf on the Pancreases of Rats Fed High Fat Diets(Taylor & Francis Ltd, 2024) Kabatas, Gul Sinemcan; Ertas, Busra; Sen, Ali; Sener, Goksel; Ercan, Feriha; Akakin, DilekWe investigated the effects of an ethanolic extract of Myrtus communis subsp. communis (MC) leaves on the pancreases of rats fed with a high fat diet (HFD). Wistar albino rats were fed either with standard lab chow (Control group) or with a 45% fat diet (HFD and HFD+MC groups) for 4 months, with the MC extract (100 mg/kg) being administered by orogastric gavage to rats in the HFD+MC group during the last month. Blood and pancreas samples were collected from all experimental groups at the end of the study. Insulin and leptin levels, and the lipid profile, were analyzed in the blood serum. Pancreatic injury was assessed histologically. Insulin, nuclear factor kappa beta (NF-kappa B), and alpha-smooth muscle actin (alpha-SMA) were assessed using immunohistochemistry. Apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) immunohistochemistry. In addition, oxidant/antioxidant activity was analyzed by biochemical methods. Increased body weight, serum insulin and leptin levels, blood glucose level and pancreatic tissue malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, myeloperoxidase (MPO) activity and decreased tissue glutathione (GSH) level were observed in the HFD group compared to the Control group, in addition to dyslipidemia. An increased histopathological damage score, pancreatic islet area, insulin, TUNEL, NF-kappa B and alpha-SMA immunoreactivity were seen in animals from the HFD group compared to the Control group. However, such pathological changes were reduced in the HFD+MC group. Our data indicate further investigation of MC extract as a therapeutic adjuvant for HFD-induced pancreatic injury, acting via anti-inflammatory and antioxidant mechanisms, is worth carrying out.Article Citation - WoS: 1Ameliorative Effects of Myrtus Communis L. Extract Involving the Inhibition of Oxidative Stress on High Fat Diet-Induced Testis Damage in Rats(Taylor & Francis Ltd, 2024) Coskunlu, Busra; Koroglu, M. Kutay; Hersek, Irem; Ertas, Busra; Sen, Ali; Sener, Goksel; Ercan, FerihaThe possible protective effects of Myrtus communis L. (MC) extract on a high fat diet (HFD)-induced testicular injury in a rat model were investigated using histological and biochemical methods. Wistar albino rats were divided into three groups: a standard diet control group; a HFD group; and an HFD+MC group. The HFD and HFD+MC groups were fed with a HFD for 16 weeks. MC extract (100 mg/kg) was given orally five days a week to the rats in the HFD+MC group during the last four weeks of the experiment. Leptin, triglyceride, high-density lipoproteins, cholesterol, estrogen, testosterone, LH and FSH were analyzed in blood serum. Sperm parameters were evaluated from the epididymis. Testicular morphology, proliferative, apoptotic and NADPH oxidase-2 (NOX2)-positive cells were evaluated histologically. Testicular oxidative stress parameters were analyzed biochemically. In the HFD group, lipid and hormone profiles were changed, abnormal spermatozoa, degenerated seminiferous tubules with apoptotic and NOX2-positive cells were increased in number, and sperm motility and germinal proliferative cells decreased compared to the control group. Moreover, testicular malondialdehyde, 8-hydroxy-2-deoxyguanosine and myeloperoxidase levels increased, whereas glutathione and superoxide dismutase levels decreased in the HFD group compared to the control group. All these histological and biochemical features were ameliorated by MC treatment of HFD-fed rats. In conclusion, HFD caused alterations in sperm parameters and testicular morphology by increasing oxidative damage and apoptosis. MC extract may have potential protective effects by inhibiting oxidative damage.