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Öğe Ameliorative effect of edible Halopteris scoparia against cadmium-induced reproductive toxicity in male mice: A biochemical and histopathologic study(Wiley, 2020) Guner, Ozlem; Guner, Adem; Yavasoglu, Altug; Karabay Yavasoglu, Nefise Ulku; Kavlak, OyaCadmium (Cd) is a toxic metal affecting the reproductive system. Halopteris scoparia (brown algae) is generally consumed as a salad in the Far East countries. This study was conducted to compare and determine the possible protective effects of H. scoparia and vitamin E and C combination (VEC) against cadmium chloride (CdCl2)-induced reproductive toxicity. A total of 36 male mice were equally divided into as control, CdCl2 (2 mg/kg), CdCl2 + H. scoparia (900 mg/kg), CdCl2 + VEC (200 mg/kg), H. scoparia alone and VEC alone groups. Blood and testis samples were taken for biochemical, histochemical and immunohistochemical analyses. H. scoparia was also examined for antioxidant activity (by DPPH assay) and mineral/trace element content (by ICP-MS method). CdCl2 exposure caused a significant deterioration in body weight, sperm parameters (count, motility, viability and morphology) (p < .001), histopathology, immunoreactivity and testosterone levels. However, H. scoparia improved CdCl2-induced deterioration effects more successfully than VEC-treated group. The present study suggests that edible H. scoparia can be used as a natural protective agent against Cd-induced testicular damage by possibly enhancing essential element levels or increasing antioxidant defence system.Öğe Assessing the Antiangiogenic Effects of Chalcones and Their Derivatives(Taylor & Francis Ltd, 2024) Burmaoglu, Serdar; Gobek, Arzu; Anil, Derya Aktas; Alagoz, Mehmet Abdullah; Guner, Adem; Guler, Cem; Hepokur, CeylanPathological angiogenesis plays a critical role in tumorigenesis and tumor progression, and anti-angiogenesis therapies have evinced promising antitumor effects in solid tumors. Chalcone skeleton has been regarded as a potential antitumor agent that also targets angiogenesis. In this study, we designed twenty-one non-fluoro-substituted chalcones (13-18, 24-27) and saturated chalcone derivatives (19-23, 28-33) as anti-angiogenic compounds. During the initial stage, these compounds were assessed for their anti-cancer activities against MCF-7 cancer cell lines according to the MTT assay. The compounds revealed satisfactory anti-proliferative capability. An ex vivo fertilized hens' egg-chorioallantoic membrane (HET-CAM) angiogenic study was conducted for the compounds to gauge their mortality and toxicity, which, in turn, revealed a potent anti-angiogenic effect. Eight compounds (16, 17, 21, 24, 26, 27, 29, and 31) significantly reduced densities of capillaries on CAM, whereas compounds 27 and 29 were the most effective anti-angiogenic agents, when compared with Suramin. Moreover, RT-qPCR analysis demonstrated that the anti-angiogenic activity was associated with the fold changes of VEGFR2. Molecular docking studies were conducted for compounds to investigate their mode of interaction within the binding site of VEGFR-2 kinases. This work provided a basis for further design, structural modification, and development of chalcone derivatives as new anti-angiogenic agents.Öğe Astaxanthin Attenuates Chlorpyrifos-Induced Pulmonary Cytotoxicity by Modulating Mitochondrial Redox and Inflammatory Pathways(Mdpi, 2025) Okudan Altindas, Mediha Demet; Guner, AdemChlorpyrifos (CPF), an organophosphate pesticide, is known to induce pulmonary toxicity through oxidative stress, mitochondrial dysfunction, and inflammation. Astaxanthin (ASX), a xanthophyll carotenoid derived primarily from marine microalgae (Haematococcus pluvialis), possesses strong antioxidant properties and has demonstrated cellular protective effects in numerous oxidative stress studies. However, its efficacy against CPF-induced lung cell damage remains uncharacterized. This study revealed the protective role of ASX, as a pretreatment and co-treatment, against CPF-induced cytotoxicity in human A549 lung adenocarcinoma cells by assessing cell viability, intracellular reactive oxygen species (IROS), total oxidative status (TOS), total antioxidant capacity (TAC), mitochondrial membrane potential (MMP), intracellular calcium ions (Ca2+), lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, DNA fragmentation, and apoptosis/inflammation-associated gene expression. CPF treatment significantly decreased cell viability and TAC, while elevating IROS, TOS, MMP, intracellular Ca2+, and LDH release. CPF also increased MDA levels and suppressed GPx and SOD activities. DNA fragmentation and quantitative polymerase chain reaction (qPCR) analysis revealed upregulation of pro-apoptotic and inflammatory markers such as BCL2-associated X protein (BAX), caspase-3 (CASP3), tumor protein p53 (TP53), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), nuclear factor kappa B (NF kappa B), and voltage-dependent anion-selective channel protein 1 (VDAC1) and suppression of anti-apoptotic B-cell lymphoma 2 (BCL2) and antioxidant defense genes nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). ASX treatment, particularly when administered as a pretreatment, significantly reversed CPF-induced oxidative and inflammatory responses by restoring SOD, GPx, and TAC levels, reducing IROS, TOS, MDA, and LDH release, and downregulating apoptotic and inflammatory gene expressions. ASX pretreatment notably decreased MMP and intracellular Ca2+ levels, indicating protection against mitochondrial dysfunction and calcium dysregulation. ASX upregulated Nrf2 and HO-1 expression and restored the BCL2/BAX balance, suggesting inhibition of mitochondrial-mediated apoptosis. Additionally, ASX significantly attenuated CPF-induced anti-angiogenic effects in the in ovo Hen's Egg Test Chorioallantoic Membrane (HET-CAM) assay. These findings demonstrate, for the first time, that ASX exerts a broad spectrum of protective effects against CPF-induced cytotoxicity in lung cells, mainly through the stabilization of mitochondrial redox status and modulation of apoptosis- and inflammation-related gene pathways, highlighting ASX as a promising candidate for further therapeutic development. Furthermore, the pronounced efficacy observed in the pretreatment regimen suggests that ASX can be evaluated as a potential nutritional preventive strategy in high-risk populations with occupational or environmental CPF exposure.Öğe Boric acid and quercetin supplementations alleviated paraquat-induced neurotoxic and irritation effects in human SH-SY5Y cells and in ovo models(Bmc, 2025) Guner, Adem; Tekin, AskinBackgroundParaquat (PQ) is a herbicide that causes neurotoxicity through oxidative stress, mitochondrial dysfunction and apoptosis. Boric acid (BA) and quercetin (Qe) are bioactive compounds with antioxidant and anti-inflammatory properties, but their combined effect against PQ-induced neuronal damage is still unexplored. This study aimed to investigate the individual and synergistic protective effects of BA and Qe in SH-SY5Y neuroblastoma cells and in ovo models.MethodsHuman SH-SY5Y neuroblastoma cells were exposed to PQ (400 mu M) with or without BA (50 mu M), Qe (50 mu M) or their combination for 48 h. ROS production, mitochondrial membrane potential (MMP, Delta Psi m) and intracellular calcium levels (Ca-2(+)) were measured. Apoptotic (BAX, BCL2, Casp-3) and inflammatory (NFKB, VEGF, TNF, TRAF1) gene expression and DNA fragmentation were determined by qRT-PCR and DPA assay. NRF2 activation was determined by gene expression. In parallel, irritation and vascularization were evaluated using the hen's egg chorioallantoic membrane (HET-CAM) assay after exposure to PQ, BA, Qe and their combinations.ResultsPQ significantly increased ROS, interfered with MMP, increased Ca-2(+) levels, regulated pro-apoptotic and inflammatory genes, and induced DNA fragmentation. BA or Qe alone reduced oxidative stress, partially restored Delta Psi m and Ca-2(+) homeostasis, downregulated BAX and Casp-3, and increased BCL2 expression. The combined treatment with BA + Qe showed the strongest protection by significantly reducing ROS, restoring Delta Psi m and Ca-2(+) homeostasis, suppressing inflammatory genes, enhancing NRF2 activation and minimizing DNA fragmentation, indicating synergistic antioxidant and anti-apoptotic effects. In the HET-CAM assay, PQ induced hemorrhage, lysis, and severe irritation with an IS of 9.1 +/- 0.2, whereas BA, Qe, and BA + Qe alone showed no irritation. Co-treatments (BA + PQ and Qe + PQ) caused moderate irritation (IS 6.2 +/- 0.1 and 6.0 +/- 0.2, respectively), while the combined treatment with BA + Qe + PQ markedly alleviated irritation, showing only mild effects (IS 4.1 +/- 0.2).ConclusionsBA and Qe, particularly in combination, protect neuronal cells from PQ-induced oxidative and mitochondrial damage by restoring redox balance, stabilizing mitochondria, regulating Ca-2(+) homeostasis and modulating apoptosis and attenuating irritation in the in ovo model. These results suggest that BA and Qe may be promising complementary therapeutics to attenuate neurotoxicity caused by environmental toxins.Öğe CD44 Targeting of Cisplatin-Loaded Hyaluronic Acid-Modified Mesoporous Silica Nanoparticles for Lung Adenocarcinoma: Synthesis, Characterization, In Vitro and In Vivo Evaluation(Mdpi, 2026) Guler, Cem; Gelen, S. Sacide; Sanci, Ebru; Buhur, Aylin; Tikir, H. Ece; Nalbantsoy, Ayse; Guner, AdemBackground/Objectives: Cisplatin (CDDP) is widely used in the treatment of non-small cell lung cancer (NSCLC); however, its clinical efficacy is limited by severe systemic toxicity. Hyaluronic acid (HA) modification enables the targeting of CD44-overexpressing cancer cells, enhances biocompatibility, provides controlled drug release, and prolongs systemic circulation. This study aimed to develop high-molecular-weight hyaluronic acid-modified, cisplatin-loaded mesoporous silica nanoparticles (HA-MSN-CDDP) to selectively target CD44-overexpressing lung adenocarcinoma cells. Methods: HA-MSN-CDDP nanoparticles were synthesized via the sol-gel method and characterized by FTIR, DLS, SEM, and TEM methods. Antitumor efficacy was evaluated using both in vitro and in vivo xenograft lung cancer models in mice. Results: HA modification enabled controlled and sustained release of cisplatin from the HA-MSN-CDDP drug delivery system. Through HA-mediated receptor-dependent endocytosis, the nanoparticles exhibited enhanced cellular uptake and selective cytotoxicity toward CD44-positive cells. HA-MSN-CDDP significantly reduced the cytotoxic, genotoxic, and oxidative stress effects of free cisplatin on healthy cells while markedly enhancing apoptosis in A549-Luc-C8 cells. The system showed excellent hemocompatibility, supporting its potential for intravenous use. In vivo, HA-MSN-CDDP effectively suppressed tumor growth, mitigated lipid peroxidation, and preserved antioxidant enzyme activities (SOD and CAT) in major organs. Histological analyses confirmed reduced cisplatin-induced nephrotoxicity. Conclusions: HA-MSN-CDDP demonstrates strong potential as a targeted chemotherapeutic platform for NSCLC, combining high antitumor efficacy with reduced systemic toxicity.Öğe Cytotoxic and oxidative stress-related effects of N2O2-type Ni(II)-thiosemicarbazone complexes: Experimental and computational studies(Elsevier Ireland Ltd, 2026) Guner, Adem; Poladian, Qumars; Karakurt, Tuncay; Ilhan-Ceylan, Berat; Sahin, Onur; Kurt, YaseminNew thiosemicarbazone-based Ni(II) complexes, [Ni(L1-3)] (1-3), were synthesized, structurally characterized, and evaluated for their cytotoxic potential in a panel of human cervical (HeLa), lung (A549), breast (MDA-MB231), and pancreatic (PANC-1) cancer cells, along with a non-cancerous human embryonic kidney (HEK-293) cell line. The complexes exhibited selective cytotoxic effects, with HeLa cells showing the highest sensitivity. Among them, complex 2 demonstrated the most pronounced antiproliferative activity and selectivity compared to complexes 1 and 3. Cellular studies in HeLa cells revealed increased oxidative stress markers, mitochondrial dysfunction, and apoptosis-related alterations accompanying the observed cytotoxicity. Chemical antioxidant assays indicated higher radical-scavenging activity for the free ligand, whereas complex 2 displayed the highest TEAC value among the metal complexes. To support the experimental findings, computational studies including quantum chemical calculations, molecular docking, molecular dynamics simulations, and MM/GBSA analyses were performed, revealing favourable electronic properties and stable interactions of the complexes with the PI3K alpha/mTOR kinase. Overall, the combined experimental and computational results highlight complex 2 as a promising Ni(II)-thiosemicarbazone scaffold with selective cytotoxic activity associated with altered oxidative stress parameters.Öğe Development of a Virtual Reality Experience Satisfaction Scale for Occupational Health and Safety Training(Lippincott Williams & Wilkins, 2026) Deniz, Fatih; Hacibektasoglu, Suleyman Enes; Tufan, Satu; Guner, Ozlem; Guner, Adem; Sahin, OnurObjectiveThis study addresses the lack of validated tools to assess satisfaction with virtual reality (VR) applications in occupational health and safety (OHS) training.MethodsA 22-item satisfaction scale was developed through item generation, expert review, and pilot testing. Data were collected from 258 participants who completed VR-based OHS training between February and June 2024. Exploratory and confirmatory factor analyses were conducted, along with internal consistency checks using Cronbach alpha.ResultsThe scale explained 70.657% of the total variance. Internal consistency was high, with Cronbach alpha values of 0.958 for Effectiveness-Learning, 0.928 for Perceived Satisfaction, 0.778 for Ease of Perception, and 0.966 overall.ConclusionsThe developed scale is a valid and reliable instrument for evaluating satisfaction with VR-based OHS training, supporting the improvement of training effectiveness and learner-centered design.Öğe Evaluation of Antiproliferative Activity and Molecular Modeling Studies of Some Novel Benzimidazolone-Bridged Hybrid Compounds(Mdpi, 2025) Guven, Okan; Mentese, Emre; Yilmaz, Fatih; Guner, Adem; Emirik, Mustafa; Caliskan, NedimeBackground/Objectives: Cancer is among the leading causes of mortality worldwide. In 2022 alone, the global cancer death toll stood at 9.74 million. Projections indicate that this figure will rise to 10.4 million by 2025. Methods: A new series of benzimidazolone-bridged hybrid compounds containing thiophene, furan, oxadiazole, piperazine, and coumarin moieties was synthesized and structurally characterized by 1H-NMR, 13C-NMR (APT), and elemental analysis. Their cytotoxic effects were evaluated by MTT assay against human lung (A549), human breast (MCF-7), and human cervical (HeLa) cancer cell lines, and the non-cancerous HEK293 cell line after 48 h exposure over a concentration range of 0.5-250 mu M. IC50 values were determined, and Selectivity Indexes (SI) were calculated using HEK293 as the reference normal cell line. Molecular docking studies were carried out using the Glide XP protocol against VEGFR2 (PDB ID: 4ASD) and CDK4-Cyclin D3 (PDB ID: 7SJ3), with sorafenib and abemaciclib as reference inhibitors. Results: The results of anticancer activity were compared with doxorubicin (IC50 +/- SD (mu M)/SI: 4.3 +/- 0.2/1.20 for A549, 6.4 +/- 0.37/0.77 for MCF-7, 3.4 +/- 0.19/1.54 for HeLa), a drug used for cancer chemotherapy. The structures of the newly synthesized hybrid compounds were identified by 1H-NMR, 13C-NMR (APT), and elemental analysis data. These hybrid compounds represent a promising class of anticancer agents. Several compounds demonstrated marked and concentration-dependent cytotoxicity across all cancer cell lines, with HeLa cells showing the highest overall sensitivity. The introduction of an oxadiazole ring (compound 7) and coumarin substituents (compounds 12b-12d) markedly improved anticancer activity and selectivity, yielding low-micromolar IC50 values in HeLa cells (10.6-13.6 mu M) and high Selectivity Indexes (SI = 2.0-3.63). Compound 6 also exhibited balanced potency across A549, MCF-7, and HeLa cells (IC50 = 28.3-31.2 mu M) with SI values >= 2.0. Compound 9 showed strong cytotoxicity across all cancer cell lines; its moderate SI values indicate lower discrimination between malignant and non-malignant cells. Taken together, these findings identified compounds 7, 12b-12d, 6, and 12c as the most promising benzimidazolone-based candidates, displaying both potent cytotoxicity and favorable selectivity over non-malignant HEK293 cells. Conclusions: Among the synthesized molecules, the oxadiazole derivative (7) and the coumarin-based hybrids (12b-12d) exhibited the strongest combination of cytotoxic activity and selectivity, reflected by their low IC50 values and high SI ratios. Notably, compound 12c combined strong biological activity with the highest predicted VEGFR2 affinity in the series, highlighting it as a particularly promising scaffold. While compound 9 exhibited excellent docking scores toward both VEGFR2 and CDK4, its lower selectivity suggests a need for further structural refinement. Overall, the biological and computational findings converge to identify these benzimidazolone hybrids as credible lead candidates for future anticancer optimization.Öğe Halopteris scoparia Overcomes Cisplatin Resistance and Their Combination Inhibits Lung Adenocarcinoma Tumor Growth: A Study on Cytotoxicity, Cell Cycle, DNA Fragmentation, Membrane Permeabilization, Oxidative Stress, Apoptosis Regulation and IVIS Imaging(Springer, 2025) Guner, Adem; Yildirim, Yeliz; Erdokur, Ozgenur; Mehmetoglu, Ayca; Yavasoglu, N. Ulku KarabayCisplatin is an effective chemotherapeutic drug but its ability is restricted by acquired resistance and its toxic effects in normal cells. Brown algae Halopteris scoparia is consumed as a salad and is known to have cytotoxic effects in human cancer cells. The present research was planned to evaluate the chemo-sensitizing potential of H. scoparia aqueous extract with cisplatin in A549 lung adenocarcinoma cells. We also investigated the cytotoxic, oxidative and genotoxic effects of H. scoparia aqueous extract on lymphocyte-cultured human blood and revealed its fatty acid profiles by GC-FID. Our results showed, via the IVIS imaging system, that a combination of H. scoparia and cisplatin significantly inhibited (98 %) tumor development in mice inoculated with A549-luc2 cells and that these effects were related to increased oxidative stress, DNA fragmentation and lactate dehydrogenase leakage levels, induced G2/M cell cycle arrest, decreased cellular antioxidant status as well as upregulations in proapoptotic genes and downregulations in antiapoptotic genes. H. scoparia extract had no cytotoxic, oxidative or genotoxic effects on lymphocytes. The results suggest that the combination regimen could inhibit tumor formation by overcoming the resistance to cisplatin, and H. scoparia can protect normal cells by decreasing the requirement of cisplatin during the chemotherapy.Öğe MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION PROTECTIVE EFFECTS OF LIGANDROL AGAINST CISPLATIN-INDUCEDMOUSE MUSCLE CELL LINE TOXICITY(Springer, 2025) Ustun, Zisan; Akkan, Tamer; Guner, AdemCisplatin is an effective chemotherapeutic agent, but skeletal muscle dysfunction and fatigue are serious side effects after its administration. Ligandrol is a new nonsteroidal oral selective androgen receptor modulator used for muscle strengthening. The present study aimed to demonstrate the protective effects of ligandrol against cisplatin-induced muscle toxicity. Cytotoxic effects were determined by cell viability (MTT) and lactate dehydrogenase (LDH) assays in mouse muscle cell lines (C2C12). The oxidant/antioxidant status was demonstrated by total antioxidant capacity (TAC) and total oxidative status (TOS). Cell cycle analysis, DNA fragmentation, caspase 3/7 activities, lipid peroxidation, and intracellular calcium concentration levels were evaluated. Irritant effects were determined by the egg chorioallantoic membrane method. Our results showed that combination treatment with cisplatin of ligandrol significantly (p < 0.05) increased cell viability, TAC levels, and caspase 3/7 gene expression, while significantly (p < 0.05) reducing TOS, LDH release, DNA fragmentation, lipid peroxidation, and intracellular calcium concentration levels compared to the cisplatin alone. Ligandrol significantly ameliorated cisplatin-induced irritant effects. This result suggested that ligandrol had a significant protective effect against cisplatin-induced muscle toxicity.Öğe Novel Adenine-Hydrazone Hybrids Against Human Lung Adenocarcinoma (A549): Design, Synthesis, Cellular Mechanistic Investigation and Molecular Docking Studies(Mdpi, 2026) Mentese, Emre; Caliskan, Nedime; Aksu, Didem; Emirik, Mustafa; Guner, Adem; Yilmaz, FatihBackground/Objectives: Adenine derivatives are promising anticancer scaffolds, but their cellular mechanisms remain unclear. This study aimed to synthesize adenine-hydrazone hybrids and evaluate their cytotoxic effects in human lung adenocarcinoma (A549) cells. Methods: A series of adenine-hydrazone compounds (3a-r) was synthesized and tested for cytotoxicity in A549 and MRC-5 cells. Selected compounds were further analyzed for LDH release, oxidative stress markers, ROS production, mitochondrial membrane potential, cell-cycle distribution, apoptosis, and in silico docking against VEGFR2, ALK5, and EGFR. Results: Compounds with electron-withdrawing or donor-acceptor substituents showed the highest cytotoxicity, while halogenated and methoxy analogs were moderately active. Among the synthesized derivatives, 4F-substituted derivatives (3c) showed more activity than 2F- and 3F-substituted ones (3a and 3b). 4F- and 3Br-substituted derivatives (3f) showed more activity than only 4F-substituted ones (3c). 4-Nitro-substituted derivative (3i) showed more activity than 4F- (3c), 4Cl- (3d) and 4OMe- (3h) derivatives. Trimethoxy-substituted derivative (3l) showed more activity than di- and mono-substituted methoxy derivatives (3g, 3h, 3j and 3k). Among the salicyl aldehydederivatives (3m-r), 4-N(et)2-substituted derivative (3r) showed more activity than non-substituted (3m), 5Br-(3n), 5Cl-(3o), 5Me (3p) and 3OCH3 (3q) derivatives. Treatment induced oxidative stress, mitochondrial depolarization, Sub-G1 cell-cycle accumulation, and apoptosis. Docking studies indicated strong binding to VEGFR2 and ALK5, suggesting dual inhibition as a potential mechanism. Conclusions: Adenine-hydrazone derivatives exert substituent-dependent anticancer effects by inducing redox imbalance-associated mitochondrial dysfunction and regulated cell death. These results highlight their potential as lead structures for lung cancer therapy.Öğe Novel Coumarin Derivatives Containing a Triazole Moiety: A Study on Synthesis, Cytotoxicity, Membrane Dysfunction, Apoptosis, Cell Cycle, and Antiangiogenic Effects(Bentham Science Publ Ltd, 2022) Guner, Adem; Bektas, Hakan; Mentese, EmreBackground: Coumarin is a functional compound with a pronounced wide range of biological activities and has recently been shown to have anticancer effects on various human cancer cells. Cisplatin is widely used in treating many cancers, but its effectiveness is limited due to acquired resistance and dose-related side effects. Objective: This study aimed to reveal the chemosensitizing ability of novel synthesized coumarin-triazole hybrid compounds (3a-f) compared to the cisplatin in A549, MCF-7, and HeLa cancer cells. Methods: Cytotoxicity was determined by MTT assay. Lactate dehydrogenase (LDH), antioxidant/oxidant status, and DNA fragmentation were determined spectrophotometrically using commercial kits. Muse (TM) Cell Analyzer was used to assess cell cycle progression. Pro/anti-apoptotic gene expressions were determined by Real-Time qPCR. The antiangiogenic activity was determined by VEGF expression and Hen's chorioallantoic membrane model. Results: Compounds 3c, -d, -e, and -f potentiated the cisplatin-induced cytotoxicity by increasing LDH release and DNA fragmentation, inducing G2/M cell cycle arrest, overproducing oxidative stress, and decreasing cellular antioxidant levels. These compounds combined with cisplatin caused upregulation in the pro-apoptotic Bax, Bid, caspase-3, caspase-8, caspase-9, Fas, and p53 gene expressions while downregulating anti-apoptotic DFFA, NFkB1, and Bcl2 gene expressions. These combinations caused vascular loss and a reduction in VEGF expression. Conclusion: These results suggest that a combinational regimen of coumarin compounds with cisplatin could enhance the effect of cisplatin in A549 cells. Besides, these compounds exhibit relatively low toxicity in normal cells, thus decreasing the dose requirement of cisplatin in cancer treatments.Öğe Oxidative stress-induced apoptotic changes after acute exposure to antifouling agent zinc pyrithione (ZnPT) in Mytilus galloprovincialis Lamark (Mediterranean mussels) tissues(Taylor & Francis Ltd, 2022) Katalay, Selma; Guner, Adem; Dagdeviren, Melih; Yigitturk, Gurkan; Yavasoglu, Altug; Gunal, A. Caglan; Yavasoglu, N. Ulku KarabayZinc pyrithione (ZnPT) is one of the components used in antifouling paints and can be an alternative to classical toxic chemicals such as organotin. However, there is still remarkable concern about the environmental safeness of ZnPT due to rapid transchelation and degradation into several metabolites that have their own toxicity. The effect after acute exposure of ZnPT is investigated on Mediterranean mussels exposed to 20 and 40 mu g/L concentrations for 48 and 96 h and antioxidant responses [superoxide dismutase (SOD), and reduced glutathione (GSH)], genotoxicity [micronuclei (MN) frequency], apoptotic and histological changes were determined. Severe histological changes in hepatopancreas and gill tissues of mussels were observed in ZnPT exposed groups due to dose-dependent increase. ZnPT also caused a dose-dependent increase of TUNEL-positive cell count in the mussel tissues, especially in the hepatopancreas. Increasing in SOD activities and decreasing in GSH levels in both ZnPT concentrations compared to the control were observed. MN and binuclei numbers in all exposure groups were significantly increased. The results of the present study demonstrate that acute exposure to ZnPT could cause an adverse effect on mussel tissues at especially higher concentrations.Öğe Polymeric nanoparticles tryptophan-graft-p(HEMA): a study on synthesis, characterization, and toxicity(Springer, 2023) Guler, Cem; Gulcemal, Suleyman; Guner, Adem; Akgol, Sinan; Yavasoglu, N. Ulku KarabayPoly-hydroxyethyl methacrylate [p(HEMA)] is one of the most widely used polymers in different biomedical applications because it is a biocompatible and a biodegradable material. Tryptophan (Trp) is a biocompatible, antioxidant, and anti-inflammatory amino acid. Trp modification contributes to the more effective use of nanoparticles in cancer therapy. The aim of this study was to synthesize polymeric nanoparticles tryptophan-graft-poly(HEMA) [Trp-g-p(HEMA)] and assess characterization and toxicity/biocompatibility potential of it in terms of using a drug carrier. The nanoparticles were synthesized with surfactant-free emulsion polymerization and grafting technique and the grafting efficiency was found as 78.65 +/- 2.48%. The characterization of the nanoparticles was performed by FT-IR spectroscopy, zeta analysis, scanning electron microscopy, atomic force microscopy, and swelling test. The nanopolymers had the spectra from 750 to 4000 cm(-1) and characteristic peaks of stretching bands, 164.1 +/- 29.2 nm average size, - 10.2 +/- 8.7 mV surface charge, smooth surface, and nearly spherical shape. The swelling ratios of them were estimated as 79.52 +/- 0.86% in d.w. and 93.33 +/- 2.32% in PBS at 25 degrees C, 35.71 +/- 0.62% in d.w., and 42.86 +/- 0.64% in PBS at 37 degrees C. The nanoparticles did not induce cytotoxicity, oxidative stress generation, and genotoxicity on human healthy lymphocyte cells. Trp-g-p(HEMA) had hemocompatible properties. We found no irritant effect in the HET-CAM test. The acute oral LD50 value of the nanopolymers was > 2000 mg/kg body weight on BALB/c mice. We announce that the polymeric nanoparticles Trp-g-p(HEMA) is a biocompatible material and has potential to use as a drug carrier for oral, intravenous, and ocular administrations.Öğe Protective Effect of Boric Acid Against Ochratoxin A-Induced Toxic Effects in Human Embryonal Kidney Cells (HEK293): A Study on Cytotoxic, Genotoxic, Oxidative, and Apoptotic Effects(Springernature, 2025) Tekin, Askin; Guner, Adem; Akkan, TamerThe present study evaluates the protective properties of boric acid (BA) against the toxic effects induced by ochratoxin A (OTA) in human embryonic kidney cells (HEK293). The focus is on various parameters such as cytotoxicity, genotoxicity, oxidative stress, and apoptosis. OTA is a known mycotoxin that has harmful effects on the liver, kidneys, brain, and nervous system. BA, on the other hand, a boron-based compound, is known for its potential as a vital micronutrient with important cellular functions. The results show that BA administration not only increases cell viability but also mitigates the cytotoxic effects of OTA. This is evidenced by a reduction in the release of lactate dehydrogenase (LDH), indicating less damage to cell membranes. In addition, BA shows efficacy in reducing genotoxic effects, as the frequency of micronucleus (MN) and chromosomal aberrations (CA) decreases significantly, suggesting a protective role against DNA damage. In addition, the study shows that treatment with BA leads to a decrease in oxidative stress markers, highlighting its potential as a therapeutic intervention against the deleterious effects of OTA. These results emphasize the need for further research into the protective mechanisms of boron, particularly BA, in combating cell damage caused by OTA.Öğe Tetrachloromethane Induced Acute Liver Injury in Mice: Biochemical and Histopathological Study of the Hepatoprotective Effect of Hep-X Standardized Botanical Dietary Supplement(Springer, 2023) Karayildirim, Cinel Koksal; Guner, Adem; Yigitturk, Gurkan; Ince, Iskender; Yasar, Mustafa; Yavasoglu, Nefise Ulku Karabay; Yavasoglu, AltugThis work was aimed at investigating the hepatoprotective effect of Hep-X, a polyherbal formulation containing Silybum marianum L. (Milk thistle), Rosmarinus officinalis L. (Rosemary), Curcuma longa L. (Turmeric) and Fumaria officinalis L. (Fumitory) as standardized botanical dietary supplement, on mice with CCl4-induced acute liver injury. The total phenolic and flavonoid contents of Hep-X were determined as 0.125 and 0.528 mg/mL, respectively. The quercetin content was determined as 50 mu g/mL using HPLC analysis. The total antioxidant capacity showed correlation between the Hep-X concentration and percentage inhibition of free radicals. Hep-X was administered orally at 25, 50 and 100 mg/kg b.w./day against CCl4-induced hepatotoxicity in mice. The hepatic damage was measured using blood biochemical parameters. Animals upon Hep-X treatment exhibited better drug effIcacy in certain blood parameters than silymarin-treated mice. Also, Hep-X administration significantly ameliorated the liver damage by suppressing iNOS expression and apoptosis as well as by recovery of the histological structure. The obtained results suggest that Hep-X is able to significantly alleviate the hepatotoxicity induced by CCl4 in mice, which can be due to antioxidant properties of the polyherbal formulation.Öğe Urea-sugar and thiourea-sugar diastereomers: synthesis, crystal structure and biological activities(Taylor & Francis Ltd, 2025) Isilar, Ozer; Bulut, Adnan; Tombul, Mustafa; Guner, Adem; Sahin, OnurAimsThe principal objective of the conducted study is to synthesize enantiomerically pure a class of sugar-based (thio)ureas (9-12) and to investigate their antiproliferative activities against the A549 (lung cancer), MCF-7 (breast cancer), and PANC1 (human pancreatic cancer) cell lines.Materials and methodsThe synthesis of (thio)urea sugars was performed by two stage procedure. First, the amino sugars (4 and 8) were obtained in three steps (tosylation, substitution and reduction). And secondly, the reaction of 3,5-bis(trifluoromethyl)phenyliso(thio)cyanate with the corresponding amines gave chiral (thio)urea derivatives (9-12). Cell viability was determined in human A549, MCF-7, PANC-1 and noncancer human embryonic kidney (HEK-293) cell lines.ResultsFour chiral sugar (thio)ureas (9-12) were synthesized and screened against the A549, MCF-7, and PANC1 cell lines. Of the four chiral sugar derivatives, the compound 9 not only showed the best anticancer activity in the A549 cell line but also provided the highest normal cell (HEK-293) viability.ConclusionFrom chiral sugar-derived (thio)ureas obtained, the compound 9 was found to be shown the highest activity against A549 cancer cell line. The compound 9, therefore, gave more promising results for future researches as anti-cancer agents. X-ray studies revealed that amide type hydrogens are playing important roles in anti-cancer activities.
