WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Protective Effects of Panax Ginseng against Bisphenol A-Induced Testicular Toxicity in Rats(Springer Nature, 2026) Cesur, Yasemin; Cam, Kamil; Pazarbasi, Seren Ede; Dorucu, Dogancan; Sener, Goksel; Abas, Burcin Irem; Cevik, OzgeBisphenol A (BPA) is an endocrine-disrupting chemical known to cause testicular toxicity through oxidative stress and apoptosis. Panax ginseng (PG) is a natural product with anti-inflammatory effects. This study aimed to evaluate the protective effect of PG against BPA-induced testicular damage in rats. Thirty-two Wistar Albino rats aged 10-12 weeks were divided into four groups: Control, PG, BPA, and BPA + PG. BPA (50 mg/kg/day) and PG (100 mg/kg/day) were orally administered for 6 weeks. BPA significantly increased serum total oxidant status and decreased antioxidant status (p < 0.001, p < 0.001). Also, the levels of superoxide dismutase (an antioxidant enzyme) (p = 0.0005) and androgen receptor-mRNA (an androgen signaling marker) decreased (p = 0.014). However, caspase 3 (an apoptosis marker) (p = 0.0067), 8-hydroxy-2'-deoxyguanosine (a marker of oxidative DNA damage) (p < 0.001), and tumor necrosis factor-alpha (a proinflammatory cytokine) (p < 0.001) levels increased in testicular tissues. Rats treated with PG showed improvements in all oxidative and inflammatory markers and significantly restored androgen receptor expression. Histopathological examination revealed degeneration in seminiferous tubules and reduced spermatozoa in the BPA group, while the BPA + PG group showed marked improvement. These findings suggest that PG may alleviate oxidative stress-related testicular damage at both molecular and histological levels and may offer insights for future clinical studies.Article Montelukast Attenuates Abdominal Aortic Aneurysm in Rats: Anti-Inflammatory and Antioxidant Effects(Elsevier, 2026) Tekin, Gozde; Cevik, Ozge; Cetinel, Sule; Sener, Goksel; Kizilay, MehmetObjective: Oxidative stress and inflammation are widely recognized as central mechanisms in the pathogenesis of abdominal aortic aneurysm. This study sought to examine the potential protective properties of montelukast in a rat model of aortic aneurysm. Methods: Male Sprague-Dawley rats were randomly allocated into three experimental groups. Abdominal aortic aneurysm was induced using the calcium chloride (CaCl2) model, in which gauze soaked in 0.5 M CaCl2 was placed directly onto the adventitial surface of the infrarenal abdominal aorta for 15 minutes. After induction, the treatment group received daily intraperitoneal injections of montelukast (10 mg/kg) for 4 consecutive weeks. At the study end point, animals were euthanized, and infrarenal aortic tissues were harvested for biochemical and histological evaluations. Measured parameters included matrix metalloproteinase (MMP)-2 and MMP-9 expression, myeloperoxidase (MPO) activity, and 8-hydroxy-2 '-deoxyguanosine levels. Antioxidant capacity was assessed through superoxide dismutase (SOD) activity assays. Histopathological examinations were performed, and statistical analysis was conducted using GraphPad Prism v.5. Results: Exposure to CaCl2 triggered pronounced oxidative injury and inflammation, as evidenced by elevated 8-hydroxy-2 '-deoxyguanosine levels, increased MPO activity, reduced SOD activity, and upregulated MMP-2 and MMP-9 expression. Montelukast administration markedly attenuated these changes, normalizing oxidative and inflammatory markers while improving histopathological architecture. Conclusions: Montelukast effectively counteracted CaCl2-induced aortic damage. The protective effects of montelukast appear to be mediated through suppression of MMP activity, restoration of SOD levels, and reduction of MPO-driven oxidative injury. By mitigating both inflammatory and oxidative mechanisms, montelukast contributes to the preservation of aortic wall structure. Clinical Relevance: Abdominal aortic aneurysm remains a major vascular disorder without an effective pharmacological therapy to slow its progression. In this experimental study, montelukast, a leukotriene receptor antagonist widely used in asthma, attenuated abdominal aortic aneurysm formation in rats and was associated with increased superoxide dismutase activity, reduced myeloperoxidase levels, and suppressed matrix metalloproteinase activation. These combined antioxidant, anti-inflammatory, and matrix-stabilizing effects preserved aortic wall integrity. Given montelukast's established safety and clinical availability, these findings support its potential for future clinical investigation as a pharmacological approach to limit aneurysm progression. (JVS-Vascular Science 2026;7:100405.)Article Design and Synthesis of Thiosemicarbazides and 1,2,4-Triazoles Derived From Ibuprofen as Potential Metap (Type II) Inhibitors(Elsevier Ireland Ltd, 2025) Yilmaz, Ozgur; Biliz, Yagmur; Ayan, Sumeyra; Cevik, Ozge; Karahasanoglu, Mufide; Cotuker, Reyhan; Kucukguzel, S. GunizIn the present study, a range of novel thiosemicarbazides 4a-i and 1,2,4-triazoles 5a-i derived from ibuprofen, were synthesized. Structural elucidation of these synthesized compounds was performed utilizing a variety of spectroscopic methods, including FTIR, 1H NMR, 13C NMR and HR-MS. The synthesized compounds were tested for cytotoxicity in five different cancer cell lines (cervical cancer (HeLa), human breast cancer (MCF-7), human gastric adenocarcinoma (MKN-45), human metastatic prostate cancer (PC3) and human glioblastoma (U87)). The compounds were compared with healthy cells (NIH-3T3) and the most effective compounds were determined by means of the selectivity index. Thiosemicarbazides derived form ibuprofen 4i and 4d showed anticancer activity, while 1,2,4-triazoles derived form ibuprofen 5b, 5c, 5d, 5e, 5h, 5g showed anticancer activity in HeLa, MCF-7, MKN-45, PC3 and U87 cells. To test the stability of the protein-drug complexes all 18 compounds 4a-i and 5a-i were docked into the active site of the MetAP2 enzyme In general, computational inhibition constants values were correlated with the experimental values. The dynamic behavior of MetAP2-inhibitor complexes was analyzed using all atoms Molecular Dynamic (MD) simulations for 200 ns duration. MD revealed that the drugs bind in the active center of MetAP2 with stable RMSD and RMSF. In conclusion, in-silico results and in-vitro studies suggests that thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen may be novel anticancer drug candidates for treating cervical, breast, prostate, gastric and glioblastoma. Compounds provided induction of apoptotic proteins in the cell by inhibiting MetAP2 enzyme. Furthermore, the potential antioxidant activities of the compounds were evaluated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay. Among the compounds tested, 4a, 4b, 4e, 4f, 4h, and 4i exhibited values closely resembling the DPPH activity of the standards.Article Citation - WoS: 10Citation - Scopus: 10Novel Azole-Urea Hybrids as Vegfr-2 Inhibitors: Synthesis,<i> In</I><i> Vitro</I> Antiproliferative Evaluation And<i> In</I><i> Silico</I> Studies(Elsevier, 2023) Shirzad, Mohammad Musa; Kulabas, Necla; Erdogan, Omer; Cevik, Ozge; Dere, Damla; Yelekci, Kemal; Kucukguzel, IlkayThe vascular endothelial growth factor receptor-2 (VEGFR-2) is a receptor tyrosine kinase known to be abnormally expressed in various malignant tumors, including breast cancer, and is considered one of the most important contributors to tumor angiogenesis. Sorafenib is one of many VEGFR-2 inhibitors that have received approval for clinical use from the US FDA in recent years. Accordingly, in this study, the synthesis of two new pyrazoles, six 1,3,4-oxadiazoles, four 1,3,4-thiadiazoles, and ten 1,2,4-triazole-3-thione derivatives having structural characteristics similar to sorafenib was carried out. A preliminary screening of synthesized compounds and known inhibitors sorafenib and staurosporine at 10 mu M concentration on in vitro activity of VEGFR-2 was performed, and compounds 10c, 8a, and 11 g were identified as the most potent derivatives with% VEGFR-2 residual activities lower than 30%, and dose-dependent inhibition studies was carried out to determine the IC50 values of these inhibitors. Compound 10c was found to be the most potent inhibitor of VEGFR-2 activity with an IC50 value of 0.664 mu M. The anti-proliferative activity of synthesized derivatives was assessed against a breast carcinoma (MCF-7) cell line, a triple negative human breast adenocarcinoma (MDA-MB-231) cell line, and noncancerous fibroblast cells (L929). Compound 8a displayed superior activity when compared to sorafenib against MCF-7 (7.69 fold) and MDA-MB-231 (1.52 fold) cell lines while displaying 3.75-fold less toxicity against the normal L929 cell line. Annexin V binding assay revealed that compound 8a significantly increased early and late apoptosis in MCF-7 cells and late apoptosis and necrosis in MDA-MB-231 cells. Computational studies such as molecular docking and ADMET evaluation were performed to elucidate the binding interactions and druglikeness of the synthesized compounds. The results indicate that compound 8a could be a promising candidate for the development of a novel anti-angiogenic and anti-proliferative agent.Article Citation - WoS: 5Citation - Scopus: 6Hepatoprotective Effects of Parsley (petroselinum Crispum) Extract in Rats With Bile Duct Ligation(Elsevier, 2023) Ede, Seren; Özbeyli, Dilek; Erdogn, Omer; Cevik, Ozge; Kanpalta, Fatma; Ercan, Feriha; Senerg, Goksel; Şener, Göksel; Erdoğan, ÖmerBackground and study aims: This study aimed to investigate the possible protective effects of parsley extract (Petroselinum Crispum; PC) against oxidative liver damage caused by bile obstruction in rats. Material and methods: Bile duct ligation (BDL) method was used to induce liver injury in rats. The rats were divided into the three groups each consisting of 8 rats; Sham-operated control (C), bile duct ligated + saline treated (BDL), and BDL + PC treated groups. PC extract was given at a dose of 2 g/kg orally for 28 days. Aspartate amino transferase (AST), alanin amino transferase (ALT), and bilirubin levels were analyzed in sera. In order to determine free radicals in liver injury, luminol and lucigenin chemiluminescence tests used. Oxidative stress was evaluated through superoxide dismutase, glutathione, malondialdehyde, Na+/K+-ATPase and 8-hydroxy guanosine levels. Furthermore, inflammation marker myeloperoxidase, apoptosis marker caspase-3, and fibrosis markers TGF- beta and hydoxyproline were investigated. The liver tissues were also examined for histological evaluations.Results: While PC treatment decreased AST and ALT levels which increased with BDL, oxidant damage parameters also decreased with this treatment. Conclusion: The present study, which is the first research for PC extract on cholestasis induced liver damage, demonstrated that PC extract could be a potential therapeutic agent against liver fibrosis and need further studies.Article Citation - WoS: 3Citation - Scopus: 5<i>cotinus Coggygria</I> Scop. Attenuates Acetic Acid-Induced Colitis in Rats by Regulation of Inflammatory Mediators(Springer, 2023) Sen, Ali; Ertas, Busra; Cevik, Ozge; Yildirim, Aybeniz; Kayali, Damla Gokceoglu; Akakin, Dilek; Sener, GokselIn traditional medicine, many medicinal plants are used in the treatment of various diseases caused by inflammation. The objective of the present study is to elucidate for the first time the effects of Cotinus coggygria (CC) ethanol extract (CCE) on colonic structure and inflammation of acetic acid-induced ulcerative colitis in rats. Colonic damage was assessed using disease activity index score, enzyme-linked immunosorbent assay, and hematoxylin-eosin staining. Also, in vitro antioxidant activity of CCE was investigated by ABTS methods. Total phytochemical content of CCE was measured spectroscopically. Acetic acid caused colonic damage according to disease activity index and macroscopic scoring. CCE significantly reversed these damages. While the levels of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and TGF-1beta increased in tissue with UC, IL-10 level decreased. CCE increased inflammatory cytokine levels to values close to the sham group. At the same time, while markers indicating disease severity such as VEGF, COX-2, PGE2, and 8-OHdG indicated the disease in the colitis group, these values returned to normal with CCE. Histological research results support biochemical analysis. CCE exhibited significant antioxidant against ABTS radical. Also, CCE was found to have a high content of total polyphenolic compounds. These findings provide evidence that CCE might be benefit as a promising novel therapy in the treatment of UC in humans due to high polyphenol content and justify the use of CC in folkloric medicine for treatment of inflamed diseases.Article Citation - WoS: 11Citation - Scopus: 11Synthesis and Biological Evaluation of Novel Aryloxyacetic Acid Hydrazide Derivatives as Anticancer Agents(Taylor & Francis inc, 2021) Senkardes, Sevil; Erdogan, Omer; Cevik, Ozge; Kucukguzel, S. GunizIn our continuing search for new anticancer agents, herein we report the synthesis of 2-(4-chloro-3-methylphenoxy)-N'-[(aryl)methylidene]acetohydrazides 3a-j and the evaluation of their anticancer activities on cell viability, morphological changes and caspase-3 activity in cancer cell lines including gastric cancer (MKN45), cervical cancer (HeLa) and breast cancer (MDA-MB-231) cells. 2-(4-chloro-3-methylphenoxy)-N'-[(4-phenylthiophen-2-yl)methylidene] acetohydrazide 3g presented the strongest growth inhibition against MKN45 gastric cancer cell lines with the IC50 value of 1.471 +/- 0.23 mu M. Moreover, compounds 3b and 3g showed high potency against the HeLa and MDA-MB-231 cell lines having IC50 in the range of 2.38-9.72 mu M. These compounds are more selective for the tested human cancer cells than for the mouse fibroblast cell line (NIH/3T3). As a result of the studies conducted in order to understand the molecular mechanism, compounds 3b and 3g enhanced expression of the caspase-3 pro-apoptotic proteins levels besides caspase-3 gene.Article Citation - WoS: 5Citation - Scopus: 5Paricalcitol Protects Against Hydrogen Peroxide-Induced Injury in Endothelial Cells Through Suppression of Apoptosis(Frontiers Media Sa, 2023) Koksal, Muhammet Murat; Sekerler, Turgut; Cevik, Ozge; Sener, AzizeThe vascular endothelium is one of the main targets of oxidative stress which plays an important role in the pathophysiology of vascular damage. Recent studies show that vitamin D can positively regulate endothelial functions in various chronic diseases and in cases of increased oxidative stress. In our study, we investigated the restorative and protective potentials of paricalcitol which is frequently used in patients with chronic renal failure, a vitamin D analogue, in human umbilical vein endothelial cells (HUVEC) before and after H2O2-induced oxidative stress. Paricalcitol treatment after the oxidative stress induced by H2O2 increased cell viability in endothelial cells depending on the dose that was used. While paricalcitol (500 nM) decreased caspase-3 activity and mitochondrial membrane potential loss, it increased nitric oxide (NO) production and reduced glutathione (GSH) levels. Paricalcitol treatment before oxidative stress increased cell viability. It increased NO production and mitochondrial membrane potential while significantly reducing caspase-3 activity. While paricalcitol caused a significant inhibition of protein disulfide isomerase (PDI) reductase activity in healthy endothelial cells, it did not cause a significant change on the PDI reductase activity under oxidative stress conditions. Present study showed that paricalcitol has restorative and protective effects on endothelial cells against oxidative injury, but these effects occur at high concentrations of paricalcitol.