Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleYalnız künye2026Scopus SJRQ1Morin counteracts KBrO3-induced hepatotoxicity by reprogramming the HOTAIR/MEG3-miR-125b-5p/miR-214-5p axis and suppressing STAT1-associated RIPK3/MLKL necroptotic signaling
Özer, Muhammed Rasit; Özdemir, Selcuk; Küçükler, Sefa; Özkaraca, Mustafa; Kizil, Hamit Emre; Akaras, Nurhan; Mutlu, Huseyin; Kandemir, Fatih Mehmet
Potassium bromate (KBrO3; PB), an oxidative contaminant in ozonated water and bakery products, induces multi-mechanistic hepatotoxicity. Its epigenetic, necroptotic, and metabolic injury dimensions remain poorly characterized. Morin (MOR), a dietary flavonoid with established antioxidant and anti-inflammatory properties, has not previously been evaluated against PB-induced subacute hepatotoxicity. To characterize MOR's hepatoprotective mechanisms against PB-induced liver injury, focusing on the HOTAIR/MEG3-miRNA epigenetic axis, STAT1-associated RIPK3/MLKL necroptotic signaling, and Glut2/HPGD-AKT/mTOR metabolic signaling. Male Sprague-Dawley rats (n = 28) were assigned to Control, MOR (100 mg/kg), PB (62 mg/kg), and PB + MOR groups for 14 days. Outcomes included hepatobiliary biochemistry, oxidative stress markers, inflammatory mediators (ELISA), lncRNA/miRNA/mRNA profiling (RT-qPCR), immunohistochemistry (RIPK3, MLKL), double immunofluorescence (Glut2/AKT1; HPGD/mTOR), histopathology, and PCA. PB produced marked redox imbalance (up arrow MDA; down arrow SOD, CAT, GPx), NF-kappa B/NLRP3-associated inflammatory mediator elevation, epigenetic disruption (up arrow HOTAIR, down arrow MEG3; up arrow miR-125b-5p/down arrow BCL2L2; down arrow miR-214-5p/up arrow SMAD4), upregulation of STAT1-associated necroptosis-related transcripts and proteins (up arrow RIPK1/RIPK3/MLKL), and metabolic dysfunction (down arrow Glut2, down arrow HPGD; up arrow AKT1/mTOR). MOR restored redox balance, suppressed inflammation, and reprogrammed the miRNA axis while normalizing MLKL (transcript and immunohistochemistry) and AKT1 and partially attenuating RIPK3, mTOR, and STAT1. MOR confers multi-targeted hepatoprotection by restoring redox and metabolic homeostasis, attenuating NF-kappa B/NLRP3-associated inflammation, reprogramming HOTAIR/MEG3-miRNA epigenetics, and attenuating STAT1-associated RIPK3/MLKL signaling, supporting its potential as a dietary hepatoprotective candidate. PB is associated with engagement of the hepatic STAT1/RIPK3/MLKL axis and disrupts the HOTAIR/MEG3-miRNA network-both previously undocumented for this toxicant. MOR partially restores miR-214-5p/miR-466 expression while suppressing their downstream effector SMAD4, consistent with attenuation of pro-fibrotic signaling. Future work should employ multi-dose designs, in vitro mechanistic dissection, sex-stratified analyses, and clinical pharmacokinetic profiling to advance MOR toward translational application.
- MakaleYalnız künye2026Scopus SJRQ2Novel heteroaromatic compounds bearing thiosemicarbazone as anti-cancer and anti-bacterial agents: Synthesis, cytotoxic and biological screening, molecular docking and DFT analysis
Nartop, Dilek; Ögütcü, Hatice; Özkan, Elvan Hasanoglu; Yetim, Nurdan Kurnaz; Kizil, Hamit Emre; Ekincioglu, Yavuz
Novel heteroaromatic compounds (Hc1, Hc2, Hc3, Hc4) were obtained, and their structure were confirmed using various spectroscopic methods, including elemental analysis, fourier transform infrared (FT-IR) spectroscopy, proton and carbon nuclear magnetic resonance (1H/13C-NMR) spectroscopy, and molar conductance measurement. The biological activities of the heteroaromatic compounds against several Gram-positive (Micrococcus luteus ATCC9341, Staphylococcus epidermidis ATCC12228, Bacillus cereus RSKK863, Listeria monocytogenes ATCC 19111), and Gram-negative bacterial strains (Pseudomonas aeruginosa ATCC27853, Klebsiella pneumonia ATCC27853, Enterobacter aerogenes ATCC51342, Salmonella typhi H NCTC9018394, Shigella dysenteriae NCTC2966, Proteus vulgaris RSKK96026) were evaluated using the well-diffusion method. In general, the heteroaromatic compounds demonstrated a stronger inhibitory effect against Gram-positive bacteria. Hc1, Hc2 and Hc3 showed the highest inhibitory effect against B. cereus and L. monocytogenes. The compound (Hc4) showed the highest antibacterial activity and antifungal activity against Bacillus cereus and C. albicans, respectively. The cytotoxic activity of the heteroaromatic compounds was assessed against the non-small cell lung cancer cell line (NCI-H460) using the NutriCulture Cell Viability Detection Kit-8 (CVDK-8). Among the synthesized heteroaromatic compounds, Hc3 exhibited significant cytotoxic activity with an IC50 value of 141.3 & micro;g/mL, whereas compounds Hc1, Hc2, and Hc4 did not display significant toxicity at the tested concentrations. The molecular geometry of the heteroaromatic compound (Hc3) was optimized using Gaussian 09 W at the B3LYP/6-311++G (d,p) level of theory. Key structural parameters such as bond lengths, bond angles, and dihedral angles were determined through the same computational framework. Electronic features, including frontier molecular orbitals, global reactivity descriptors, and molecular electrostatic potential surfaces, were analyzed to explore intramolecular charge distribution and predict reactive sites. To evaluate the biological potential of the heteroaromatic compound (Hc3), molecular docking studies were performed. Additionally, drug-likeness assessment based on Lipinski's Rule of Five and ADME profiling revealed favorable pharmacokinetic characteristics. Molecular docking studies revealed that compound Hc3 showed a binding energy of -4.09 kcal/mol against the EGFR target (PDB ID: 1UWH), exhibiting key interactions such as hydrogen bonding and It-interactions with the active site residues. Based on all the results, it can be said that new heteroaromatic compounds have significant potential in the pharmaceutical field.
AtıfScopus1OpenAlex1
İncele - MakaleAçık Erişim2025Scopus SJRQ2Biosynthesis of Functionalized Silver Nanomaterials Utilizing Seeds of Black Rosehip (Rosa pimpinellifolia L.) and its Remarkable Antioxidative Capacity
Kizil, Hamit Emre
Background: Silver nanoparticles (AgNPs) have gained significant attention due to their unique antimicrobial, catalytic and optical properties. This study focuses on the green synthesis of silver nanoparticles using black rosehip (Rosa pimpinellifolia L.) seeds (Rp-AgNPs) and evaluates their biological activities. Methods: Rp-AgNPs were synthesized using R. pimpinellifolia seed extract and characterized using multiple analytical techniques including UV-Vis spectroscopy, XRD, FTIR, TEM, SEM, EDAX, zeta potential analysis, DSC, SERS and XPS. The biological activities were assessed through DPPH free radical scavenging assay, cytotoxicity testing against H460 lung cancer cells and antimicrobial activity evaluation against various pathogens. Result: The synthesized Rp-AgNPs exhibited spherical morphology with an average size of 51.27 nm and demonstrated stability with a zeta potential of-18.9. The nanoparticles showed enhanced antioxidant activity (IC50 = 30.89 μg/mL) compared to the seed extract (IC50 = 136.4 μg/mL). Cytotoxicity studies revealed significant effects against H460 cells with an IC50 of 65.8 μg/mL. Antimicrobial testing demonstrated effectiveness against both Gram-positive and Gram-negative bacteria (MIC 50-100 μg/mL) and Candida strains (MIC 100-200 μg/mL).
AtıfScopus1WoS1OpenAlex1İncele - MakaleAçık Erişim2024Determination of Cytotoxic and Apoptotic Properties of Lobaric Acid, a Secondary Metabolite of Lichen and Investigation of Its Theoretical Potential
Kizil, Hamit Emre; Agar, Guleray; Ekincioğlu, Yavuz
In this study, we aimed to elucidate some of the mechanisms of cell death induced by lobaric acid in A549 (human lung cancer) cells. For this purpose, the effects of cytotoxic concentrations on p53 and caspase-3 gene expressions were investigated. A549 cells were treated with varying concentrations of lobaric acid (12.5, 25, 50, and 100 µg/ml) for 48 hours and then their viability was evaluated and p53 and caspase-3 mRNA expressions were determined at statistically cytotoxic concentrations of 12.5, 50, and 100 µg/ml. According to beta-actin, it was determined that the increase in lobaric acid concentration revealed an upward trend in p53 and caspase-3 mRNA expressions. Furthermore, quantum chemical parameters such as frontier molecular orbitals, band gap energy and ionization potential, electronic affinity, chemical softness, chemical potential, electrophilicity index and chemical hardness were analyzed. Furthermore, molecular docking was performed to identify the binding sites and the binding behavior of lobaric acid to some target proteins (P53, Caspase-3 and Bcl-2).
AtıfOpenAlex3
İncele - MakaleAçık Erişim2024Phytochemical Analysis and Determination of Antioxidative, Antimicrobial And In Vitro Cytotoxic Properties of Black Rosehip (Rosa Pimpinellifolia L.) Fruits Growing in The Northeast of Türkiye
Bayram, Sinan; Kizil, Hamit Emre; Kıcık, Büşra
The aim of this study was to determine the phenolic content of Rosa pimpinellifolia (L.) fruit extract and antibacterial, antioxidant activity and show the cytotoxic effects of different concentrations of Rosa pimpinellifolia L. fruit extract obtained by ultrasonic assisted method on MCF-7 cell line by WST-8 assay. Antibacterial effects analyzed by disk diffusion method and determined that there was no antibacterial effect in 500 μg/mL Rosa pimpinellifolia L. fruit extract dose. In addition, the total phenolic content was determined by the Folin-Ciocalteu method and found that total phenolic content is 37.5±0.2 mg GA/g. Antioxidant activity value was determined as 32.06±1.1 mg TE/g by ABTS method and 23.47±1.6 mg TE/g by DPPH method. The highest cytotoxic effect of Rosa pimpinellifolia L. fruit extract was determined in dose of 40 μg/mL on MCF-7 cell.
AtıfOpenAlex1İncele - MakaleAçık Erişim2023Determination of the cytotoxic effect of Prangos ferulacea (L.) Lindl. which grows naturally in the foothills of Bayburt Kop Mountain, on non-small lung cancer
Kizil, Hamit Emre
The genus Prangos has been used for centuries as an antibacterial and antidiabetic agent. In this study, Prangos ferulacea (L.) Lindl. species, which is frequently encountered in various regions of our country, especially in Northeast Anatolia, and known as "çaşır or çakşır" among the people, were collected from the flora of Bayburt Kop Mountain, and methanol extract of the stem parts of this plant was obtained. Afterward, the cytotoxic effect of this extract on the non-small cell lung cancer cell line (H-460) was determined and compared with the cytotoxic activity on the lung fibroblast cell line (MRC-5). The results obtained using the Wst-8 method, it was determined that no toxic effect occurred in the MRC-5 cell line after both 24 and 48 hours of methanol extract treatment, while a toxic effect occurred in the H-460 cell line (125 μg/ml and 62.5 μg/ml) after 48 hours of application. However, this toxic effect was not statistically significant.
AtıfOpenAlex1İncele - MakaleAçık Erişim2023Could eumelanin molecule from Streptomyces parvus BSB49 strain be a potential anticancer agent for lung cancer?
Karakas, Ümıt; Bayram, Sinan; Kizil, Hamit Emre; Öztürk, Serdar
Melanins, which are divided into five different subgroups as eumelanin, pheomelanin, allomelanin, neuromelanin and pyomelanin, are a heterogeneous and amor- phous biopolymer family. Although melanin is produced in many different ways today, it is more practical, and more economical to produce melanin using bacterial strains. The eumelanin pigment, which is the subject of this study, was obtained using Streptomyces parvus BSB49 strain, and its antiproliferative effect at various concentrations against small cell (DMS-114) and non-small cell (H-460) lung cancer was determined. According to our results, the synthesized eumelanin molecule was statistically cytotoxic on non-small cell lung cancer cell line (H-460) at concentrations of 3.125 and 1.56 μg/mL after 24 hours of treatment (IC50=8 μg/mL) and only at a concentration of 3.125 μg/mL after 48 hours of treatment (IC50=8.4 μg/mL). In the small cell lung cancer cell line (DMS-114), no statistically cytotoxic concentration was detected (p<0.05).
- MakaleAçık Erişim2020Asimetrik Schiff Bazı Ni(II) Komplekslerinin Antimutajenik Aktivitesinin Değerlendirilmesi
Nartop, Dilek; Özkan, Elvan Hasanoğlu; Kizil, Hamit Emre; Agar, Guleray; Sarı, Nurşen
Bu çalışmada, asimetrik Ni(II) kompleksleri (NiL1, NiL2, NiL3, NiL4) potansiyel antimutajen özelliklerini incelemek için son zamanlarda grubumuzdan biri tarafından rapor edilen yeni iki aşamalı bir yöntem ile hazırlandı. Lenfositlerdeki sodyum azid kaynaklı antimutagenik etki, kardeş kromatid değişimi (SCE) ve mikronükleus (MN) yöntemleriyle belirlendi. Sentezlenen bileşiklerin antimutagenik özelliklere sahip olduğu ve pozitif kontrol olarak kullanılan sodyum azid (NaN3) 'ün neden olduğu mutajeniteyi azalttıkları belirlenmiştir.
AtıfOpenAlex3İncele - MakaleYalnız künye2018Scopus SJRQ2Anti-genotoxic Effects of Schiff bases and their Mn(III) Complexes Containing L-Aspartic acid and L-Phenylalanine
Hasanoglu Özkan, Elvan; Kizil, Hamit Emre; Sakiyan, Iffet; Nartop, Dilek; Sari, Nursen; Agar, Guleray
The purpose of the research was to evaluate the genotoxic and anti-genotoxic properties of Schiff bases and their Mn (III) complexes containing L-aspartic acid, and L-phenylalanine. The anti-genotoxic properties of four compounds in human lymphocytes cells were investigated by sister chromatid exchanges (SCEs) test system against aflatoxin Bi (AFBi). The results showed that compounds have strong anti-genotoxic properties.
AtıfWoS3İncele - MakaleAçık Erişim2018Scopus SJRQ3The anti-genotoxic effect of some lichenic acids
Kizil, Hamit Emre; Ceker, Selcuk; Capik, Ozel; Agar, Guleray
Four lichen secondary metabolites; diffractaic acid, lecanoric acid, lobaric acid and vulpinic acid were evaluated for the anti-genotoxic effects on human lymphocytes in vitro using single cell gel electrophoresis (SCGE) or comet assay. Carbon tetrachloride, a known mutagenic agent was used as the positive control in the comet test system. The results revealed that at all concentrations, the tested compounds mediated a significant decrease in total DNA damage (comet assay) as compared with positive controls (p > 0.05). The most effective doses of lichen acids were found to be 100 μgmL-1 of diffractic acid, lobaric acid and vulpinic acid, and 50 μgmL-1 of lecanoric acid. In addition, it was determined that the most effective among the tested compounds was vulpinic acid.
AtıfScopus4WoS2OpenAlex2İncele - BildiriAçık Erişim2017Scopus SJRQ1Antiproliferative and apoptotic properties of vulpinic acid on A549, AGS and HeLa cells
Kizil, Hamit Emre; Agar, Guleray
- BildiriAçık Erişim2017Scopus SJRQ1Determination of the Antigenotoxic effects of Evernic acid against genotoxic effects of CCL4 on HUVEC lines
Agar, Guleray; Kizil, Hamit Emre; Ceker, Selcuk; Capik, Ozel; Sengul, Bulent
- BildiriAçık Erişim2015Scopus SJRQ1Antiproliferative effects of Evernic acid on A549 and healthy human cells: An in vitro study
Kizil, Hamit Emre; Agar, Guleray; Anar, Mustafa
AtıfWoS3OpenAlex4İncele - BildiriAçık Erişim2015Scopus SJRQ1Determination of cytotoxic and proliferative effects of 2-amino-5-nitrobenzonitrile on AGS cancer cell line
Anar, Mustafa; Kizil, Hamit Emre; Agar, Guleray
- MakaleAçık Erişim2015Scopus SJRQ2Genotoxic and antigenotoxic potentials of two Usnea species
Ceker, Selcuk; Orhan, Furkan; Kizil, Hamit Emre; Alpsoy, Lokman; Gulluce, Medine; Aslan, Ali; Agar, Guleray
For ages, lichens have long been investigated popularly for biological roles, mainly antitumor, antimicrobial and antioxidant activities. Many positive results were obtained in these previous research. Thus, in this study, we aimed to determine whether extracts of Usnea articulata (UAE) and Usnea filipendula (UFE) possessing a protection against aflatoxin B1(AFB1)-induced genotoxic and oxidative damage. The results of our studies showed that 5 μM concentrations of AFB1increased the frequencies of sister chromatid exchange (SCE) and the level of malondialdehyde (MDA) and decreased the activities of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx). However, when 5, 10 and 20 µg/mL concentrations of UAE and UFE was added to AFB1, the frequencies of SCE and MDA level were decreased and SOD, GSH and GPx level were increased. The Ames (Salmonella typhimurium TA1535, TA1537) and WP2 (Escherichia coli) test systems carried out evinced that UAE and UFE possess any mutagenicity, but have antimutagenic effects. Consequently, the results of this experiment have clearly shown that UAE and UFE have strong antioxidative and antigenotoxic effects that are associated with its antioxidant nature. A detailed study can be performed to determine the antioxidant properties of each compound that will extend the use of lichen extracts in food and pharmacy industries.
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İncele - MakaleYalnız künye2015Scopus SJRQ3Determination of antigenotoxic effects of four lichen species by using human lymphocytes
Anar, Mustafa; Asian, Ali; Ceker, Selcuk; Kizil, Hamit Emre; Alpsoy, Lokman; Agar, Guleray
In this study, the geno-toxic and antigeno-toxic properties of the total extracts of four lichen species were investigated by using human lymphocytes. We obtained total extracts from R farinacea, X. parietina, U. articulataand U. filipendula lichen species. The results of our studies showed that 5 μM concentrations of AFB1 changed the frequencies of micronucleus (MN) and malondialdehyde (MDA) levels, as well as superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx) activities. When 5,10 and 20 μg/ml concentrations of total extract were added to AFB1, the frequencies of MN and MDA levels were decreased, and SOD, GSH and GPx levels were increased. Consequently, our findings show that four lichen total extracts have strong antigenotoxic properties against aflatoxin Bi.
AtıfScopus3İncele - BildiriAçık Erişim2014Scopus SJRQ1The determination of antioxidative effect and anticancer potential of vulpinic acid
Anar, Mustafa; Kizil, Hamit Emre; Agar, Guleray
AtıfOpenAlex1İncele - BildiriAçık Erişim2014Scopus SJRQ1Cytotoxic and antiproliferative effects of evernic acid on HeLa cell lines: A candidate anticancer drug
Kizil, Hamit Emre; Agar, Guleray; Anar, Mustafa
AtıfWoS6OpenAlex10İncele - MakaleAçık Erişim2013Scopus SJRQ4Protective Role of Mentha longifolia L. ssp. longifolia against Aflatoxin B
Ceker, Selcuk; Agar, Guleray; Alpsoy, Lokman; Nardemir, Gokce; Kizil, Hamit Emre; Mete, Ebru
The aim of this study was to investigate the effects of essential oil of Mentha longifolia L. ssp. longifolia, used since ancient times for the treatment of many digestive tract diseases, on the genotoxicity and oxidative stress by a single dose of Aflatoxin B1 (5 μM) in the human lymphocyte culture. The total of the 12 identified components accounted for 97.69 % by Gas chromatography (GC). Major components of the oil were cis-piperitone epoxide (26.52 %), piperitenone oxide (26.40 %), pulegone (15.66 %) and piperitenone (13.57 %). According to the results obtained from GC-MS systems, monoterpenes consist of 89.19 % of the total oil approximately while sesquiterpenes were represented in small quantities in the oil. We studied the anti-genotoxic effects of essential oils of M. longifolia (MEO) by using sister chromatid exchange (SCE) and micronucleus (MN) test systems. Also, the anti-oxidative effects of MEO were evaluated by using superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) assay. The SCE frequency and the number of MN were increased when treated with AFB1. Especially, MEO at 1.5 and 2.0 μl reduced SCE frequency and MN number in the human lymphocyte (p <0.05). In addition, AFB1 treatment significantly reduced the activity of SOD and GPx and elevated the level of MDA (p<0.05). MEOs treatment led to significant attenuation of AFB1-induced oxidative stress by normalization of the activities of SOD and GPx and the MDA (p < 0.05). These results suggest that MEOs could provide anti-oxidative and anti-genotoxic protection for the oxidative and genotoxic agents that cause many diseases including cancer and neurodegenerative disease.
AtıfScopus10WoS11OpenAlex11İncele - MakaleYalnız künye2012Scopus SJRQ4Investigation of anti-oxidative and anti-genotoxic effects of Origanum vulgare L. essential oil on human lymphocytes in vitro
Ceker, Selcuk; Agar, Guleray; Nardemir, Gokce; Anar, Mustafa; Kizil, Hamit Emre; Alpsoy, Lokman
Origanum vulgare L. (Lamiaceae) is a flavoring herb widely using around the world. Some preparations and extracts from O. vulgare have been used in Turkish traditional medicine to treat several ailments including digestive disorders and menstrual problems. This study is designed to examine the chemical composition and in vitro antigenotoxic and antioxidant activity of the essential oil of O. vulgare (OVE) from Turkey. The essential oil of O. vulgare was analized by using GC. OVEs that were investigated antagonistic effects against oxidative stress and the genotoxic effects of aflatoksin B1 (AFB1). Anti-genotoxic activity was evaluated by sister chromatid exchanges (SCEs) and micronucleus (MN) tests. In additional to investigating protective role of OVEs against the oxidative stress of AFB1 in vitro, oxidative status was assessed on erythrocytes by measuring following oxidative stress markers like; super oxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA).The total of the 25 identified components are accounted for 96.03 % (GC). Major components of the oil were β-caryophyllene (20.40%), and caryophyllene oxide (34.44%). In the SCE and MN tests, it was observed that OVEs suppressed the mutagenic effects of AFB1. OVEs were observed to modulate the adverse effects of AFB1. The results of this experiment clearly reveal that OVEs have strong anti-oxidative and anti-genotoxic effect. These anti-genotoxic effects of O. vulgare essential oils are probably related to its action on the enzymatic activation system. Anti-oxidative and anti-genotoxic effect may be role of these compounds (β-caryophyllene and caryophyllene oxide).
AtıfScopus14WoS16OpenAlex12İncele