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    Effects of in vitro Amitriptyline, Fluoxetine, Tranylcypromine and Venlafaxine on Saphenous Vein Grafts
    (Soc Brasil Cirurgia Cardiovasc, 2019) Akinci, Melek; Karadag, Cetin Hakan; Huseyin, Serhat; Oltulu, Cagatay; Canbaz, Suat; Gunduz, Ozgur; Topuz, Ruhan Deniz
    Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3x10(-6)M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10(-11)-3x10(-5)M, while venlafaxine was added in the range of 10(-9)-3x10(-5)M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.
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    Evaluation of Genotoxicity Risk in Health Care Workers Exposed to Antineoplastic Drugs
    (Marmara Univ, Inst Health Sciences, 2019) Oltulu, Cagatay; Yesil Devecioglu, Tugce; Akinci, Melek; Olmez, Sevcan Gul Akgun; Obeidin, Serra Vildan Akgul; Beceren, Ayfer
    Objective: DNA damage that can be caused by workplace exposure to antineoplastic drugs in health workers has been shown in many scientific studies. It is aimed to evaluate whether the risk of genotoxicity in health workers decreases after the regulations and measures taken by national and international health authorities in our work. Methods: For this purpose, DNA damage was assessed by using alkaline comet technique in lymphocytes isolated from blood samples of health workers (n=29) who were involved in preparing and/or administering antineoplastic agent at Trakya University Health Research and Application Center and compared with the control group (n=30). Also, those who prepare and/or administer antineoplastic agents; (n=16) and manual (n=13) preparations. Results: As a result of the evaluation, there was no statistically significant difference between health personnel and control group in preparing and / or administering antineoplastic agent (p>0,05, Mann-Whitney U) and there was no difference in the genotoxic risk between preparation forms. Furthermore, when the exposed control group was assessed for DNA damage as smokers and nonsmokers, there was no statistically significant difference in terms of DNA damage (p>0.05). Conclusion: At the center where our samples were taken, the resulting measures resulted in the control of the risk of genotoxicity due to occupational exposure to antineoplastic agents.
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    Galangin Protects AML-12 Cells Against Dactinomycin Induced Hepatotoxicity
    (Galenos Publ House, 2023) Akinci, Melek; Oltulu, Cagatay; Bakar, Elvan; Cevikelli Yakut, Zatiye Ayca
    Aim: The purpose of this study was to evaluate the effects of galangin (Gal) on dactinomycin induced hepatotoxicity in vitro. Materials and Methods: AML -12 cell line was divided into 4 groups as the control, Gal, dactinomycin, and Gal+dactinomycin groups. IC50 dose was determined by the thiazolyl blue tetrazolium bromide test. Gene expressions of glutathione (GSH), superoxide dismutase (SOD), catalase, caspase 3 (Cas-3), Cas-9, apoptotic protease activating factor -1 (Apaf-1), B cell CLL/lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), tumor protein p53 (p53), second mitochondria -derived activator of caspase/direct inhibitor of apoptosis-binding protein (smac/DIABLO), topoisomerase (Top) I, and Top II were determined with quantitative real-time polymerase chain reaction analysis. Results: Dactinomycin elevated the expression of SOD, catalase, and GSH in response to oxidative effects. In the Gal+dactinomycin group, Gal administration reduced Apaf-1 expression and increased Bcl-2 expression with antiapoptotic effects. In the dactinomycin group, p53 levels increased due to the defense mechanism against DNA damage. Gal increased smac/DIABLO expression to remove damaged structures. Bcl-2 and smac/DIABLO expression levels in the groups were inversely proportional. In the Gal+dactinomycin group, Top II expression level was lower than in the dactinomycin group. This result indicated that double strand of DNA damage was diminished by Gal. Conclusion: Gal protected against the hepatotoxicity due to dactinomycin with antioxidant and antiapoptotic effects. Further experimental studies are needed to establish the use of Gal in liver damage.
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    Investigation of genotoxicity risk in healthcare workers that has occupational exposure to antineoplastic drugs
    (Elsevier Ireland Ltd, 2017) Oltulu, Cagatay; Akinci, Melek; Yesil, Tugce; Akgul, Vildan; Akgun, Sevcan; Motor, Deniz; Canbaz, Suat
    [Abstract Not Available]
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    Puerarin Protects from Methotrexate Induced Hepatotoxicity in AML-12 Cells
    (Galenos Publ House, 2023) Akinci, Melek; Oltulu, Cagatay; Bakar, Elvan; Cevikelli Yakut, Zatiye Ayca
    Aim: The purpose of this study was to look into the effects of puerarin (PR) on methotrexate (MTX)-induced hepatotoxicity in vitro. Materials and Methods: We designed our research with four groups in the AML-12 cell line: control, PR, MTX, and PR+MTX groups. Administered concentration levels to the cell lines were determined with the MTT test. To investigate oxidative stress, the expression levels of glutathione, superoxide dismutase, and catalase were determined with quantitative real-time-polymerase chain reaction (qRT-PCR) analysis. To evaluate the role of apoptosis pathways in MTX induced hepatotoxicity and the hepatoprotective effects of PR, gene expressions of caspase 3 (Cas-3), Cas-9, apoptotic protease activating factor-1, Bcl-2, Bax, p53, second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein (smac/DIABLO), topoisomerase (Top) I, and Top II were investigated with qRT-PCR. Results: MTX impaired the antioxidant defense through SOD but elevated the expression of catalase and glutathione due to an increase in free radicals. In the PR+MTX group, SOD expression increased and catalase and glutathione expression decreased compared to the MTX group. Cas-9, Apaf-1, and Top I gene expression levels were reduced in group PR. In the group of PR+MTX, PR application increased the expression of Bax, p53, and smac/DIABLO while decreasing the expression of Bcl-2, which resulted in the elimination of damaged structures by apoptosis. Conclusion: PR alleviated the hepatotoxicity caused by MTX with its antioxidant effects and positive effects on apoptosis pathways. However, different dose studies are needed because PR could not prevent double-strand damage in DNA due to MTX and there is an increase in Top I expression in the PR group.