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GARİP, GÜNSELİ AYŞE

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GARİP

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GÜNSELİ AYŞE

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2019 - 201912020 - 20231
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    PublicationOpen Access
    Investigation of effects of transferrin-conjugated gold nanoparticles on hippocampal neuronal activity and anxiety behavior in mice
    (2023-08-01) GARİP, GÜNSELİ AYŞE; Yavuz Y., Yesilay G., Guvenc Tuna B., Maharramov A., Culha M., Erdogan C. S., GARİP G. A., Yilmaz B.
    Gold nanoparticles (GNPs) have been widely used in medicine such as imaging, drug delivery and therapeutics due to their multifunctional properties. Alterations in neuronal function may contribute to various neurological diseases. Transferrin plays a primary role in iron transportation and delivery and has recently been utilized for drug delivery to the brain. We have investigated effects of transferrin-conjugated GNPs (Tf-GNPs) on anxiety and locomotor behavior in vivo and also hippocampal neuronal activity ex vivo. Electrophysiological effects of Tf-GNP on hippocampal neurons were determined by patch clamp method. Fifteen male young adult C57BL/6 mice were randomly divided into three groups as control (200 µL PBS), GNP (bare GNP; 2.2 μg/g in PBS) and Tf-GNPs (2.2 μg/g Tf-GNP). Animals intraperitoneally received the respective treatments for seven consecutive days and were subjected to elevated plus maze (EPM) and open field tests (OFT). Ex vivo, firing frequency of the neurons significantly increased by GNP treatment (p < 0.001). In vivo, animals in Tf-GNP group showed significantly longer distance in open arms but significantly lower number of entries to the open arms in EPM (p < 0.05). Mice received bare GNPs had significantly higher locomotor activity in OFT (p < 0.05), while Tf-GNP did not alter the locomotor activity significantly (p = 0.051). Animals in Tf-GNP group spent significantly longer time in the peripheral zone in OFT (p < 0.05). The present findings have shown that Tf-GNP induces anxiety-like behavior without altering spontaneous firing rate of hippocampal neurons. We suggest that neurobiological effects of Tf-GNP should be pre-determined before using in medical applications.
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    PublicationOpen Access
    Synergistic Effects of 4-Aminopyridine and Paclitaxel on MCF 7 Cell Line
    (MARMARA UNIV, INST HEALTH SCIENCES, 2019-09-15) GARİP, GÜNSELİ AYŞE; Aydogmus, Esra M. Cuce; Garip, Gunseli Ayse Inhan
    Objectives: Aim of this study is to increase the effectiveness of paclitaxel (PTX) with the use of 4 - aminopyridine (4-AP) on breast cancer cell line MCF-7. Methods: In this study, L-929 (ATCC CRL-6364) and MCF-7 (ATCC - HTB 22) cell lines were used. IC50 and survival values were determined by trypan blue exclusion; cell cycle analysis was determined by measuring levels of Cdk2 and Histone (H3) and plasma membrane potential (Vm) measurements were performed using fluorescent Bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBaC4(3)). Results: IC50 values were determined for two agents and these values were combined. Combination treatments ie. 4-AP (4 mM) + PTX (5 nM) and 4-AP (4 mM) + PTX (7.5 nM) decreased viability 17% +/- 8.08 and 45% +/- 3.18, respectively for L-929 cells and decreased viability 60%+/- 3.7 and 74%+/- 2.6, respectively for MCF-7 cells. For L-929 cells, plasma membrane potential measurements resulted in depolarization for 4-AP, PTX (5 nM) and PTX (7.5 nM), and resulted in hyperpolarization for the combinations. For MCF-7 cells, plasma membrane potential measurements resulted in depolarization for 4-AP, PTX (7.5 nM) and 4-AP + PTX (5 nM), and resulted in hyperpolarization for PTX (5 nM) and 4-AP + PTX (7.5 nM). Changes of Cdk2 and H3 levels showed mostly G1 arrest for MCF-7 cells and G2/M arrest for L-929 cells. Conclusions: Combination treatments increased the cell death for MCF-7 cells. But, combination treatments didn't show synergistic effect on L-929 which is accepted as a non-cancerous cell. These data showed that use of 4-AP in combination with the anticancer agent paclitaxel is a promising approach for cancer treatment.