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    Beta-glucan effects on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in liver and brain
    (Taylor & Francis Ltd, 2022) Turkmen, Nese Basak; Ozek, Dilan Askin; Taslidere, Asli; Dogan, Fatih; Ciftci, Osman
    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental contaminant that is toxic to brain, heart, kidney and liver. TCDD toxicity is due to free radical formation. Beta-glucan is an antioxidant that exhibits beneficial effects on health. We investigated the effects of beta-glucan on brain and liver tissues of rats with TCDD induced toxicity. We used female rats divided into four groups: control, TCDD group treated with TCDD 2 mu g/kg/week, beta-glucan group treated with 50 mg/kg/day beta-glucan for 3 weeks, TCDD + beta-glucan group treated with 2 mu g/kg/week TCDD and 50 mg/kg/day beta-glucan together for 3 weeks. We found that the thiobarbituric acid reactive substance (TBARS) levels were increased significantly in the TCDD group compared to the other groups. Glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were reduced in the TCDD group compared to the control group. SOD, CAT, GPx activities and GSH levels were increased in the TCDD + beta-glucan group. Histopathological observations were consistent with our biochemical findings. The oxidative stress and histopathology caused by TCDD were ameliorated by beta-glucan treatment. Beta-glucan should be explored for preventing brain and liver damage caused by TCDD toxicity.
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    Dose dependent cytotoxic activity of patulin on neuroblastoma, colon and breast cancer cell line
    (2021) Turkmen, Nese Basak; Yuce, Hande; Ozek, Dilan Askin; Aslan, Sumeyye; Yasar, Seyma; Unuvar, Songul
    Aim: Patulin, a mycotoxin, is an organic compound classified as a polypeptide. Patulin, which is generally detected in moldy fruits and their derivatives, has been suggested to have anticancer activity. Some studies have shown that it induces apoptosis in the cell. This study aims to investigate the anticancer activity of patulin in SH-SY5Y (human neuroblastoma cell line), HCT116 (human colon cancer cell line), and MCF-7 (human breast cancer cell line) cell lines. Materials and Methods: SH-SY5Y, HCT116, MCF-7, and L929 (healthy fibroblast) cell lines were used for cytotoxicity experiments. Cells were added in 96-well plates at 5x103 cells per well. Serial dilutions of patulin at a dose of 1, 2.5, 5, 10, 25, 50, and 100 µM were added to the waiting cells in 24 hours incubation. All cell lines were exposed to patulin for 24 and 48 hours. The cytotoxic activity of patulin in cancer and healthy cell lines was determined in vitro by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium) cell viability test. The results of the toxicity tests were measured spectrophotometrically (450 nm) in ELISA at intervals of 24 hours for 2 days. Results: Patulin caused cytotoxic activity in all cell lines at a concentration of 100 µM. Patulin showed cytotoxic activity at low doses only in the SH-SY5Y cell line. At doses of 25 and 50 µM, HCT116 caused more than 50% death in the cell line, while higher concentrations induced cell death in the MCF-7 cell line. Conclusion: Patulin showed anticancer activity at high concentrations in colon and breast cancer cell lines, and both low and high concentrations in the SH-SY5Y cell line. Patulin may be a new candidate molecule in the treatment of neuroblastoma, colon, and breast cancers, depending on the dose.
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    Dose dependent cytotoxic activity of patulin on neuroblastoma, colon and breast cancer cell line
    (2021) Türkmen, Neşe Başak; Yüce, Hande; Ozek, Dilan Askin; Aslan, Sumeyye; Yaşar, Şeyma; Ünüvar, Songül
    Aim: Patulin, a mycotoxin, is an organic compound classified as a polypeptide. Patulin, which is generally detected in moldy fruits and their derivatives, has been suggested to have anticancer activity. Some studies have shown that it induces apoptosis in the cell. This study aims to investigate the anticancer activity of patulin in SH-SY5Y (human neuroblastoma cell line), HCT116 (human colon cancer cell line), and MCF-7 (human breast cancer cell line) cell lines. Materials and Methods: SH-SY5Y, HCT116, MCF-7, and L929 (healthy fibroblast) cell lines were used for cytotoxicity experiments. Cells were added in 96-well plates at 5x103 cells per well. Serial dilutions of patulin at a dose of 1, 2.5, 5, 10, 25, 50, and 100 µM were added to the waiting cells in 24 hours incubation. All cell lines were exposed to patulin for 24 and 48 hours. The cytotoxic activity of patulin in cancer and healthy cell lines was determined in vitro by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulphophenyl)-2H-tetrazolium) cell viability test. The results of the toxicity tests were measured spectrophotometrically (450 nm) in ELISA at intervals of 24 hours for 2 days. Results: Patulin caused cytotoxic activity in all cell lines at a concentration of 100 µM. Patulin showed cytotoxic activity at low doses only in the SH-SY5Y cell line. At doses of 25 and 50 µM, HCT116 caused more than 50% death in the cell line, while higher concentrations induced cell death in the MCF-7 cell line. Conclusion: Patulin showed anticancer activity at high concentrations in colon and breast cancer cell lines, and both low and high concentrations in the SH-SY5Y cell line. Patulin may be a new candidate molecule in the treatment of neuroblastoma, colon, and breast cancers, depending on the dose.
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    Drug-Drug Interaction of Aldehyde Oxidase Inhibitor and Xanthine Oxidase Inhibitor with Favipiravir
    (2022) Ozek, Dilan Askin; Keskin, Zeliha; Yüce, Hande; Türkmen, Neşe Başak; Aslan, Sumeyye; Ünüvar, Songül
    Aim: Favipiravir is an effective antiviral used in the treatment of COVID-19. It is metabolized by aldehyde oxidase (AO) and xanthine oxidase (XO). This study investigated drug-drug interactions between favipiravir with both AO substrate and XO enzyme inhibitor, allopurinol, and an XO inhibitor, verapamil. Material and Methods: 25 Sprague-Dawley female rats, 250-300 g, were divided into five equal groups. Blood samples were taken from the jugular vein at the end of 0, 15, 30, and 45 minutes, and at the end of the 1st, 2nd, 4th, 6th, and 8th hours after the drugs were administered. The drug-blood concentration was determined in the HPLC-UV device using plasma. The ELISA method measured AO and XO enzyme activities in rat liver tissue. Results: Allopurinol prolonged the time taken for favipiravir to reach Cmax (Tmax), decreased maximum serum concentration (Cmax), elimination half-life (T1/2), area under the curve (AUC), and mean residence time (MRT). Allopurinol significantly reduced clearance per unit time (Cl/f) when co-administered with favipiravir. Verapamil accelerated the elimination of favipiravir, significantly reducing T1/2, MRT, and AUC. On the other hand, Favipiravir decreased the absorption of verapamil and slowed its elimination. Cmax, AUC, and Cl values of verapamil decreased. In addition, T1/2, MRT, and volume of distribution (Vd) increased. Conclusion: In conclusion, the concomitant use of favipiravir with other drugs that affect AO and/or XO enzyme activities may cause changes in the pharmacokinetic profiles of drugs and the levels of enzymes that metabolize drugs.
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    Investigation of the Protective Effect of Nerolidol on Dehydroepiandrosterone-induced Polycystic Ovary Syndrome in Female Rats
    (Wiley, 2023) Yuce, Hande; Turkmen, Nese Basak; Aydin, Muhterem; Taslidere, Asli; Dogan, Aysegul; Ozek, Dilan Askin; Hayal, Taha Bartu
    [Abstract Not Available]
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    Nerolidol attenuates dehydroepiandrosterone-induced polycystic ovary syndrome in rats by regulating oxidative stress and decreasing apoptosis
    (Pergamon-Elsevier Science Ltd, 2023) Turkmen, Nese Basak; Yuce, Hande; Aydin, Muhterem; Taslidere, Asli; Dogan, Aysegul; Ozek, Dilan Askin; Hayal, Taha Bartu
    Aims: Although nerolidol (NRL) is a naturally occurring sesquiterpene alcohol with many pharmacological ac-tivities, its role in dehydroepiandrosterone DHEA-induced polycystic ovary syndrome PCOS is unknown. This study aims to explore the potential beneficial effects and underlying molecular mechanisms of nerolidol treat-ment on polycystic ovary syndrome.Main methods: Pre-pubertal female Sprague-Dawley rats were randomly assigned into four groups (n = 8/group); group I: control; group II: PCOS; group III: P + NRL; group IV: NRL. Biochemical parameters related to oxidative stress, inflammation, apoptosis, and hormones were estimated in the blood and ovarian tissues. Histopatho-logical, ultrastructural, and immunohistochemical analyses were performed. Bax, P53, Cas-3, and Bcl-2 gene expression levels were detected with RT-PCR. The membrane array analysis detected chemokine, cytokine, and growth factor protein profiles.Key findings: In light of the available data, it can deduce that nerolidol has a significant ameliorating effect on lipid peroxidation, oxidative stress, inflammation, histopathological damage, and apoptosis accompanying PCOS in female rats.Significance: PCOS is not only a reproductive pathology but also a systemic condition and its etiopathogenesis is still not fully understood. Since changes in PCOS have important long-term effects on health, this study evaluated the efficacy of nerolidol, a phytotherapeutic for the control of biochemical, apoptotic, histopathological, and metabolic changes.
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    Protective Role of Diospyros lotus L. in Cisplatin-Induced Cardiotoxicity: Cardiac Damage and Oxidative Stress in Rats
    (Galenos Publ House, 2022) Turkmen, Nese Basak; Ozek, Dilan Askin; Taslidere, Asli; Ciftci, Osman; Saral, Ozlem; Gul, Cemile Ceren
    Objectives: Cisplatin is a powerful chemotherapeutic drug that is used to treatment a wide variety of cancers. Despite clinical data demonstrating the cardiotoxic effect of cisplatin, few studies have been carried to improve the cardiotoxicity of cisplatin. In cisplatin-induced toxicity, oxidative stress plays a critical role. This study determined the effect of Diospyros lotus L. fruit (DL), a powerful antioxidant plant, on heart damage caused by cisplatin through histological examination and oxidative stress parameters. Materials and Methods: Twenty eight male rats were randomly divided into four groups. An isotonic solution was given to the control group. A single dose of 7 mg/kg cisplatin was administered intraperitoneally to the cisplatin group. 1.000 mg/kg DL was given by gavage for 10 days to the DL group. Cisplatin and DL were administered together in the same doses to the treatment group. Thiobarbituric acid reactive substances (TBARS) levels, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and total glutathione (GSH) level were measured in the heart tissue of the experimental rats. Histological examination was also performed to determine any damage to the hearts of the experimental rats. Results: While TBARS levels in the cisplatin group increased significantly, SOD, CAT, GPx activities, and total GSH level decreased significantly. TBARS levels decreased significantly and SOD, CAT, GPx activities and GSH levels increased with DL treatment. According to the histological examination, histopathological differences were observed in the cisplatin group. Histopathological findings were either absent or decreased in the DL-treated group. Conclusion: Results of the study showed that DL therapy reduced oxidative stress and histological changes caused by cisplatin. DL could be a potential candidate for reducing cardiac damage caused by cisplatin.