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    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, Oya
    Cadmium (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.
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    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, Ceylan
    Pathological 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.
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    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 Karabay
    Cisplatin 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.
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    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, Emre
    Background: 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.
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    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 Karabay
    Zinc 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.
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    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 Karabay
    Poly-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.
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    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, Tamer
    The 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.
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    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, Altug
    This 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.