Browsing by Author "Cevik, Ozge"
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Article Citation Count: 4Bitter Melon (momordica Charantia) Fruit Extract Ameliorates Methotrexate-Induced Reproductive Toxicity in Male Rats(Marmara Univ, Fac Medicine, 2021) Şener, Göksel; Ozbeyli, Dilek; Sen, Ali; Cevik, Ozge; Sener, Goksel; Ercan, Feriha; Eczacılık Meslek Bilimleri BölümüObjective: Methotrexate (MTX) is a drug commonly used for the treatment of malign neoplastic and inflammatory diseases. Anti-oxidant and anti-inflammatory effects of bitter melon (BM) were reported. The aim of this study was to examine the effects of BM fruit extract on MTX-induced testicular and epididymal damage. Materials and Methods: Sprague Dawley male rats were divided into three groups (n=8) as control, MTX and MTX+BM. A single dose of MTX (20 mg/kg) was injected intraperitoneally to the MTX and MTX+BM groups. BM fruit extract (600 mg/kg) was applied to the MTX+BM group orally for 5 days. Testes were examined for general histopathology, proliferating and apoptotic cells. The epididymis samples were used for the evaluation of sperm morphology. Oxidative and inflammatory markers were analysed biochemically. Results: Increased abnormal spermatozoa, degenerated seminiferous tubules with increased apoptotic cells and decreased proliferative cells were observed in the MTX group. TNF-alpha, IL-1 beta, 8-hydroxy-2-deoxyguanosine and caspase-3 levels increased, superoxide dismutase and catalase levels decreased in both testis and epididymis samples. All these histological and biochemical parameters were ameliorated in the MTX+BM group. Conclusion: Methotrexate causes testis damage by decreasing spermatogenic cells and increasing apoptosis through oxidative stress and inflammation. BM extract improves testis and epididymis damage with its possible anti-oxidant and anti-inflammatory effects.Article Citation Count: 0The Effect of myrtus Communis L. Extract on Nephrolithiasis Model in Rats(Kare Publ, 2024) Şener, Göksel; Dorucu, Dogancan; Gulerturk, Oznur; Sen, Ali; Cevik, Ozge; Cetinel, Sule; Sener, Goksel; Eczacılık Meslek Bilimleri BölümüOBJECTIVE: Nephrolithiasis is a common urological disease that can lead to renal failure. Oxidative stress has been shown to be a contributing factor for nephrolithiasis and many agents have been studied to prevent and treat oxidative stress-related nephrolithiasis and renal damage. Myrtus communis (MC) extract has been shown to be an important antioxidant in different animal models. In this study, MC extract was administered preventively or therapeutically to rats with kidney stones, and its effectiveness was investigated. METHODS: Wistar albino rats were divided into four groups (n=8); control (C), ethylene glycol (EG), EG+preventive MC, and EG+curative MC groups. The nephrolithiasis model was created by adding 0.75% EG to drinking water for 8 weeks. Ultimately, 24-hour urine was collected to measure calcium, citrate, and creatinine levels. After decapitation, kidney tissues were harvested for histological analyses, measurement of osteopontin and 8-hydroxydeoxyguanosine (8-OHdG) levels, and N-acetyl-beta-glucosaminidase (NAG), myeloperoxidase (MPO) and caspase-3 activities. RESULTS: In 24-hour urine samples, calcium, citrate and creatinine levels were decreased in the EG group, while oxalate levels were increased and in treatment groups these parameters returned to control levels. MPO, 8-OHdG, caspase-3 and NAG activity were significantly increased in tissue and these changes were reversed in both MC groups. Histological findings also supported the biochemical parameters. CONCLUSION: MC can reduce oxidative stress and histopathological changes in kidney tissues in rat nephrolithiasis model when used as either a preventive or therapeutic agent. If supported with further clinical trials, MC might have clinical implications in preventing oxidative renal cell injury and ultimately kidney stone formation.Article Citation Count: 3Hepatoprotective Effects of Parsley (petroselinum Crispum) Extract in Rats With Bile Duct Ligation(Elsevier, 2023) Ede Pazarbaşı, Seren; Şener, Göksel; Erdogn, Omer; Cevik, Ozge; Kanpalta, Fatma; Ercan, Feriha; Senerg, Goksel; Eczane Hizmetleri Bölümü; Eczacılık Meslek Bilimleri BölümüBackground 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 Count: 2cotinus Coggygria Scop. Attenuates Acetic Acid-Induced Colitis in Rats by Regulation of Inflammatory Mediators(Springer, 2023) Şener, Göksel; Ertas, Busra; Cevik, Ozge; Yildirim, Aybeniz; Kayali, Damla Gokceoglu; Akakin, Dilek; Sener, Goksel; Eczacılık Meslek Bilimleri BölümüIn 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 Count: 1Investigation of the Protective and Therapeutic Efficacy of myrtus Communis Extract in Aluminum Chloride and Dgalactose-Induced Alzheimer's Disease in Rats(Marmara Univ, 2022) Şener, Göksel; Sen, Ali; Cevik, Ozge; Kadioclu-Yaman, Beril; Ertas, Biiva; Yildiz, Sila; Sener, Goksel; Eczacılık Meslek Bilimleri BölümüThis study investigated the possible protective and therapeutic effects of Myrtus communis subsp. communis ethanol extract (MC) in aluminum chloride (AlCl3) and D-galactose (D-Gal) induced Alzheimer's disease in rats. MC was orally given to rats as a protective treatment for 90 days and, in other two groups starting from the 60th day MC (100-200 mg/kg) was administered, concomitantly with AlCl3 and D-Gal. Learning and memory functions were evaluated by the behavioral tests. Biological activities of MC treatment were examined in hippocampal tissues by ELISA tests. D-Gal and AlCl3-treated rats showed increased amyloid beta (A ss) and 8-hydroxy-2-deoxyguanosine (8OHdG) levels, acetylcholinesterase activity and decreased neprilysin, Na+-K+ATPase and SOD levels in parallel with a decrease in Novel Object Recognition Test, Morris Water Maze and Passive Avoidance Test scores. On the other hand, MC administration reversed the behavioral impairments and improved learning and memory. Moreover, MC treatment decreased A ss and 8-OHdG levels and acetylcholinesterase activity and increased neprilysin levels, Na+-K+ATPase and SOD levels. Our results suggest that MC has beneficial effects on cognitive and neuronal functions through its anticholinesterase and antioxidant properties.Article Citation Count: 3Novel Azole-Urea Hybrids as Vegfr-2 Inhibitors: Synthesis, In Vitro Antiproliferative Evaluation And In Silico Studies(Elsevier, 2023) Küçükgüzel, İlkay; Kulabas, Necla; Erdogan, Omer; Cevik, Ozge; Dere, Damla; Yelekci, Kemal; Kucukguzel, Ilkay; Eczacılık Meslek Bilimleri BölümüThe 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 Count: 3Paricalcitol Protects Against Hydrogen Peroxide-Induced Injury in Endothelial Cells Through Suppression of Apoptosis(Frontiers Media Sa, 2023) Şener, Azize; Sekerler, Turgut; Cevik, Ozge; Sener, Azize; Temel Eczacılık Bilimleri BölümüThe 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.Article Citation Count: 0Protective Effects of momordica Charantia (bitter Melon) Against Methotrexate-Induced Kidney Damage(Bentham Science Publ Ltd, 2023) Şener, Göksel; Ozbeyli, Dilek; Cevik, Ozge; Cetin, Melisa; Sener, Goksel; Ozkan, Sevil; Eczacılık Meslek Bilimleri BölümüBackground Methotrexate is a cytotoxic chemotherapeutic agent that has severe side effects, such as nephrotoxicity. Momordica charantia is a bright yellow-orange fruity plant that has been shown to have antioxidant, antidiabetic, and anti-inflammatory properties. Objective This study scrutinized the protective effects of Momordica charantia extract against methotrexate-induced nephrotoxicity. Methods 24 Sprague Dawley male rats were divided into three experimental groups (8 rats in each): Control (C); Methotrexate (MTX); and Methotrexate plus Momordica charantia (MTX+MC). All rats were fed ad libitum and tap water. Methotrexate was administered at 20 mg/kg intraperitoneally as a single dose. In the MTX+MC group, MC was administered at a dose of 50mg/kg for 5 days orally. At the end of the 5th day, the rats were decapitated and kidney samples were taken to analyze glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and caspase-3 activity. Data was analyzed with GraphPad Prism 5.0. Results Findings showed that while there was a significant increase in MDA, MPO, 8-OHdG levels, and an essential reduction in GSH levels in the MTX-treated group when compared with the control group, bitter melon treatment significantly reversed MDA, MPO, and 8-OHdG levels (p< 0.001). GSH level elevation was observed in the MTX-MC group when compared to the MTX-treated group (p< 0.001). Conclusion This study showed that bitter melon is thought to have a protective effect against kidney damage caused by methotrexate. With future studies, we believe that the use of bitter melon extract as a protective agent in kidney damage caused by drug-induced oxidative damage will bring an innovative approach to treatment.Article Citation Count: 0The Protective Effects Of Momordica Charantia Fruit Extract in Methotrexate Induced Liver Damage in Rats(Galenos Publ House, 2022) Ede Pazarbaşı, Seren; Şener, Göksel; Cevik, Ozge; Erdogan, Omer; Kaya, Ozlem Tugce Cilingir; Ede, Seren; Sener, Goksel; Eczane Hizmetleri Bölümü; Eczacılık Meslek Bilimleri BölümüBACKGROUND/AIMS: Methotrexate (MTX), a cytotoxic therapeutic agent, is used for the cure of malignancies and rheumatologic disorders. However, the significant side effects of MTX limits its use. In this study, we aim to assess the hepatoprotective properties of Momordica charantia (MC) against MTX-induced liver damaged in rats.MATERIALS AND METHODS: Following one dose of MTX (20 mg/kg), the rats were given either distilled water or MC extract (300 mg/kg, po) for 5 days. After the dissection of the rats, the liver was removed to analyse tumour necrosis factor -a (TNF-a), interleukin-113 (IL-113), transforming growth factor 13 (TGF-13) and 8-hydroxy-2'-deoxy-guanosine (8-OhdG) levels and superoxide dismutase (SOD), catalase (CAT), and caspase-3 activities. The tissues were also examined histopathologically.RESULTS: The hepatic TNF-a, IL-113, TGF-13, 8-OhdG levels, and Caspase-3 activity in the MTX group were found to be significantly increased compared to the control group. However, MC extract was able to significantly decrease TNF-a, TGF-13, 8-OhdG levels, and Caspase-3 activity. Also, both the SOD and CAT activity of the MTX group decreased compared to the control group. Although only the SOD levels elevated significantly with MC treatment, the SOD and CAT activities of the MC treated group were similar to the control group. Supporting these biochemical parameters, MTX-induced histologic alterations in the liver were also ameliorated via MC treatment.CONCLUSION: Our results demonstrated that MC has a protective role against MTX-induced hepatic tissue injury by reducing apoptosis, oxidative damage, and the expression of pro-inflammatory cytokines.Article Citation Count: 9Synthesis and Biological Evaluation of Novel Aryloxyacetic Acid Hydrazide Derivatives as Anticancer Agents(Taylor & Francis inc, 2021) Küçükgüzel, Şükriye Güniz; Erdogan, Omer; Cevik, Ozge; Kucukguzel, S. Guniz; Eczacılık Meslek Bilimleri BölümüIn 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.