Eczacılık Meslek Bilimleri Bölümü Koleksiyonu

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https://hdl.handle.net/20.500.12418/436

Listeleniyor 1 - 12 / 12

Mechanism of anticancer effect of ETP?45658, a PI3K/AKT/mTOR pathway inhibitor on HT?29 Cells
(27. 10. 2023) Fatih Yulak; Ahmet Kemal Filiz; Ziad Joha; Mustafa Ergul
The PI3K pathway plays a crucial role in tumor cell proliferation across various cancers, including colon cancer, making it a promising treatment target. This study aims to investigate the antiproliferative activity of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor, on colon cancer and elucidate the underlying mechanisms. HT-29 colon cancer cells were treated with varying doses of ETP 45658 and its cytotoxic effect assessed using the XTT cell viability assay.ELISA was also used to measure TAS, TOS, Bax, BCL-2, cleaved caspase 3, cleaved PARP, and 8-oxo-dG levels. Flow cytometry was performed to investigate apoptosis, cell cycle, caspase 3/7 activity, and mitochondrial membrane potential. Additionally, following the administration of DAPI (4,6-diamidino-2 phenylindole) dye, the cells were visualized using an immunofluorescence microscope. It was observed that ETP-45658 exerted a dose-dependent and statistically significant antiproliferative effect on HT-29 colon cancer cells. Further investigations using the IC50 dose showed that ETP-45658 decreased TAS levels and increased TOS levels and revealed that it upregulated apoptotic proteins while downregulating anti-apoptotic proteins. Our findings also showed that it increased Annexin V binding, arrested the cell cycle at G0/G1 phase, induced caspase 3/7 activity, impaired mitochondrial membrane potential, and ultimately triggered apoptosis in HT-29 cells. ETP-45658 shows promise against colon cancer by inducing cell death, and oxidative stress, and arresting the cell cycle. Targeting the PI3K/ AKT/mTOR pathway with ETP-45658 offers exciting potential for colon cancer treatment.
The Role of Nitric Oxide Pathway in the Anti-Epileptogenic Effect of Valproic Acid in the Pentylenetetrazole-Kindling Model in Rats
(02. 06. 2023) Bilal Sahin; Ahmet Kemal Filiz; Ziad Joha
Though valproic acid (VPA) is used to treat seizures, more investigations have been needed to understand the effect of VPA on the nitric oxide pathway in epilepsy. Our investigation aimed to study the effect of VPA on cortical and hippocampal NOS isomers in epileptogenesis processes in the PTZ kindling model of epilepsy in the rat to reveal its mechanisms of action. Twenty-four male Wistar albino rats were used in this study. The animals were divided into four groups control, PTZ without VPA, and PTZ with VPA at two doses (100 and 200 mg/kg) Rats were kindled by injections of PTZ (35 mg/kg) with drugs or vehicle 30 minutes before, once every other day for 12 times and their behavior was observed. After completing the epileptic model process, nitric oxide pathway markers (eNOS, nNOS, iNOS, and NO) in the cortex and hippocampus were assessed by using ELISA methods. VPA suppressed seizure stages and decreased nNOS, iNOS, and NO levels while increasing eNOS levels in the hippocampus and cerebral cortex. The effect of VPA on nitric oxide pathway was found to contribute to its anti-epileptic activity.
Investigation of the effect of sugammadex on glutamateinduced neurotoxicity in C6 cell line and the roles played by nitric oxide and oxidative stress pathways
(August 2023) Hasan Dirik; Ziad Joha
This experiment was intended to evaluate the effect of sugammadex on the cytotoxicity induced by glutamate, involving the nitric oxide and oxidative stress pathways. C6 glioma cells were used in the study. Glutamate was given to cells in the glutamate group for 24 h. Sugammadex at different concentrations was given to cells in the sugammadex group for 24 h. Cells in the sugammadex + glutamate group were pre-treated with sugammadex at various concentrations for 1 h and then exposed to glutamate for 24 h. XTT assay was used to assess cell viability. Levels of nitric oxide (NO), neuronal nitric oxide synthase (nNOS), total antioxidant (TAS), and total oxidant (TOS) in the cells were calculated using commercial kits. Apoptosis was detected by TUNEL assay. Sugammadex at concentrations of 50 and 100 μg/mL significantly enhanced the cell viability in C6 cells after the cytotoxicity induced by glutamate (p < 0.001). Moreover, sugammadex considerably decreased the levels of nNOS NO and TOS and the number of apoptotic cells and increased the level of TAS (p < 0.001). Sugammadex has protective and antioxidant properties on cytotoxicity and could be an effective supplement for neurodegenerative diseases such as Alzheimer and Parkinson if further research in vivo supports this claim.
Anticancer activity of lycopene in HT?29 colon cancer cell line
(24. 03. 2023) Dilara Ataseven; Ayşegül Öztürk; Mustafa Özkaraca; Ziad Joha
An inverse association between serum lycopene levels and the risk of cancers has been pointed out by many prospective and retrospective epidemiological studies which prompted more studies to be performed on animal models and cell cultures in order to test this hypothesis. The aim of the present study was to evaluate the antiproliferative and pro-apoptotic effect of lycopene on colon cancer HT-29 cell line. The effect of lycopene on the viability of HT-29 cell line was investigated using XTT assay. The levels of Bcl-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG in lycopene-treated HT-29 cells were measured using ELISA. Gamma-H2AX and cytochrome c expression was assessed semi-quantitatively using immunofluorescence staining. Lycopene at doses of 10 and 20 μM produced a significant antiproliferative effect on HT-29 cells compared to the control (p < 0.05). The IC50 value of lycopene in HT-29 cells was found to be 7.89 μM for 24 h. Lycopene (7.89 μM) significantly elevated cleaved caspase 3 (p < 0.01), BAX, and cleaved PARP, 8-oxo-dG levels (p < 0.05). The levels of γ-H2AX foci are significantly higher while the levels of cytochrome-c are lower (p < 0.05) in lycopene-treated HT-29 cells. These results indicate that lycopene has an antiproliferative apoptotic and genotoxic effect on HT-29 colon cancer cell line.
Pharmaco-Metabolomics: Drug Effects on Metabolites
(Nova Science Publishers, 2023) Sönmez Gürer, Eda
The development and advancements in technology, artificial intelligence, and fields of bioinformatics, enabled the use of enormous data coming from genes, transcripts, and proteins processed by the omics in medicine as biomarkers. Scientists are improving different methods, such as stemcell therapies, applications of regenerative medicine, and enhanced drug interactions in personalized medicine, using omics technologies in a broad scope of biology. Thus, the omics can discern functions of individual genes, proteins, and metabolites; to evaluate drug effects of drugs made or derived from such substances; and analyze differences in cellular pathways that occur from these drugs. The combined use of omics with system biology in regenerative medicine research, and pharmacology fields increases the information regarding concealed molecular mechanisms of diseases, their potential therapies, and personalized applications of stem-cell applications. Improved characterization of living systems along with a detailed evaluation of clinical and pharmacological data are required aspects for the further development of studies containing multiple omics methodologies. The application of data mining on the present data from the literature would enable to obtain experimental evidence in a cost-effective manner by reducing the prior experimental research. Metabolomics pharmacology serves to attain personalization in medicinal treatments to preserve health and prevent diseases. Different branches of omics, such as metabolomics, transcriptomics, proteomics, and toxicogenomics, would lead to improved and easier use of pharmacometabolites in treatment protocols.
Phenolic content, antioxidant and antimicrobial activities evaluation and relationship of commercial spices in the lebanese market
(Kasım 2023) Sönmez Gürer, Eda; Rayess, Youssef El; Nehme, Lea; Ghanem, Chantal; Beyrouthy, Marc El; Sadaka, Carmen; Azzi-Achkouty, Samar; Nehme, Nancy; Sharifi-Rad, Javad
AbstractLebanese cuisine is renowned for its distinctive flavours and vibrant aromas. In Lebanese cuisine, spices are not just used for their flavour; they are also valued for their medicinal properties. This study consists of evaluating and comparing the total phenolic content and the antioxidant capacity of 21 samples of spices used in the Lebanese daily diet, such as cinnamon, allspice, coriander, cloves, etc. and the mixtures prepared in well-defined proportions. Several solvents were tested for the extraction of the phenolic compounds from spices, and the water and ethanol (v/v) mixture were retained for this study. Results showed that clove presented the highest polyphenol content (173.7 ± 2.98 mg Gallic Acid Equivalent (GAE)/g Dry Matter (DM)) and the highest antioxidant capacity by ABTS test (4875.68 ± 480.40 µmol trolox / g DM). and DPPH test (85.84 ± 0.5%). The examination of the results showed a positive significant correlation between the polyphenol contents and the antioxidant activity of the spices. The antimicrobial activity tested by the broth microdilution method was determined against Escherichia coli, Listeria monocytogenes, Staphylococcus aureus and Salmonella Enteritidis. The results showed high antimicrobial activity manifested by low value of minimum inhibitory concentration (MIC) (MIC < 2.4 µg/mL) for cinnamon, turmeric, white pepper, red pepper, allspice, clove and nutmeg. In conclusion, spices used in Lebanese cuisine, such as clove, cinnamon, allspice and spices, were rich in phenolic compounds and presented important potential health benefits.
Comparative analysis of pre-fermentation treatments on phenolic compounds and bioactivity in Vitis Vinifera var. Syrah and var. Cabernet Sauvignon grapes
(Mayıs 2023) Sönmez Gürer, Eda; Ghanem Chantel; Bouajila Jalloul; Rizk Ziad; Beyrouthy Marc El; Sadaka Carmen; Souchard Jean Pierre; Taillandier Patricia; Sharifi-Rad Javad; Nehme Nancy; Rayess Youssef El
This study investigated the effect of pre-fermentation treatments on the phenolic compounds and biological activities of red grapes of Vitis vinifera var. Syrah and var. Cabernet Sauvignon Syrah and Cabernet sauvignon musts from two different regions and consecutive vintages. Specifically, cold soak at 10 °C and heat maceration at 60, 70, and 80 °C were compared to classical winemaking (maceration and fermentation at 25 °C). High-performance liquid chromatography/diode array detector (HPLC/DAD) was used to characterize the main classes of polyphenolic substances, and biological activities were determined through assays for antioxidant, anti-inflammatory, anti-hyperuricemic, anti-Alzheimer, anti-diabetic, and antiproliferative activities. The findings showed that temperature played a significant role in anthocyanin and tannin extraction. The data also revealed moderate positive correlations between dimers procyanidin B1, B2, and caffeic acid with antioxidant activities (ABTS and DPPH), a strong positive correlation between gallic acid and anti-inflammatory activity, another strong positive correlation between gallic acid and anti-diabetic activity, and a moderate correlation between anticancer activity in human breast cancer cells (MCF7) with resveratrol. In conclusion, this study provides valuable insights into the effects of different pre-fermentation treatments on the phenolic composition and biological activities of Syrah and Cabernet sauvignon musts, which may have implications for the development of new winemaking techniques.
Comparison of Chemical Profiles of Aronia melanocarpa Fruit Extracts
(Şubat 2023) Karadağ, Ayşe Esra; Altıntaş, Ayhan; Sönmez Gürer, Eda
The chokeberry plant, which is native to North America and the south of Canada, is a deciduous, shrub-shaped, berry-like plant belonging to the Rosaceae family, which survives for many years. It is seen as a plant that adapts easily to almost every climatic condition and soil and has many beneficial properties for health. Within the scope of this study, methanol, 70% ethanol, ethanol, ethyl acetate, hexane and water extracts were prepared from the fruits collected from the Aronia melanocarpa (Michx.) Elliott plant, which is cultivated in the Kırklareli region. The chemical contents of the obtained extracts were clarified by high performance liquid chromatography. It was determined that phenolic compounds such as ferulic acid, caffeic acid, quercetin, quercetin-3-galactoside, p-coumaric acid were found in the extracts, and ethyl acetate extract was found to have the richest phenolic substance profile. Malvin anthocyanin compound was detected only in methanol extract.
Novel ultra-stretchable and self-healing crosslinked poly (ethylene oxide)-cationic guar gum hydrogel
(Ekim 2023) Sönmez Gürer, Eda; Alberto Bernal‑Chávez, Sergio; Alcalá‑Alcalá Sergio; M. Almarhoon, Zainab; Turgumbayeva, Aknur; De Los Dolores, Campos‑Echeverria Ma; Cortes, Hernan; Romero‑Montero, Alejandra; Del Prado‑Audelo9, Maria Luise; Sharifi-Rad Javad; Leyva‑Gómez Gerardo
AbstractHydrogels are three-dimensional structures with specific features that render them useful for biomedical applications, such as tissue engineering scaffolds, drug delivery systems, and wound dressings. In recent years, there has been a significant increase in the search for improved mechanical properties of hydrogels derived from natural products to extend their applications in various fields, and there are different methods to obtain strengthened hydrogels. Cationic guar gum has physicochemical properties that allow it to interact with other polymers and generate hydrogels. This study aimed to develop an ultra-stretchable and self-healing hydrogel, evaluating the influence of adding PolyOX [poly(ethylene oxide)] on the mechanical properties and the interaction with cationic guar gum for potential tissue engineering applications. We found that variations in PolyOX concentrations and pH changes influenced the mechanical properties of cationic guar gum hydrogels. After optimization experiments, we obtained a novel hydrogel, which was semi-crystalline, highly stretchable, and with an extensibility area of approximately 400 cm2, representing a 33-fold increase compared to the hydrogel before being extended. Moreover, the hydrogel presented a recovery of 96.8% after the self-healing process and a viscosity of 153,347 ± 4,662 cP. Therefore, this novel hydrogel exhibited optimal mechanical and chemical properties and could be suitable for a broad range of applications in different fields, such as tissue engineering, drug delivery, or food storage.
Pharmacokinetic Profiles of Metamizole Metabolites after Intramuscular and Intravenous Administration in Healthy Arabian Horses
(2021) Yılmaz, İsmet; Maraş,Zeynep; Uğur, Yılmaz; Özgür, Mustafa Erkan; Durmaz, Murat; Ulusoy, Halil İbrahim; Erdoğan, Selim
Metamizole sodium (MT) is an analgesic and antipyretic drug molecule used in humans, horses, cattle, swine, and dogs. Metamizole rapidly hydrolyzes and turns into methyl amino antipyrine (MAA), an active primary metabolite of MT. The present study aims to determine the pharmacokinetic (PK) profiles of MT metabolites after intravenous (IV) and intramuscular (IM) administration into sex of Arabian horses (Equus ferus ca ballus) using a cross-over study design. The plasma samples were extracted by solid phase extraction (SPE) method, and plasma concentrations of MT metabolites were analyzed by high-performance liquid chromatography (HPLC). After administrations of MT, plasma concentrations of methylamino antipyrine (MAA), amino antipyrone (AA), and acetylamino antipyrone (AAA) were determined within range of 15 min 12 h. Plasma concentrations of AA and AAA were lower than the plasma concen trations of major metabolite MAA at each sampling point. The PK parameters were statistically evaluated for MT’s metabolites between male and female horses and also between IM and IV administrations of PK parameters such as Cmax, tmax, t1/2λz, AUC0-t , AUC0-∞, λz, Cl and Vss (p < .05). The AUCIM/AUCIV ratio in female and male horses for MAA was 1.19 and 1.13, respectively. The AUCIM/AUCIV ratio for AA was lower than those found for MAA. AUCIM/AUCIV ratio was statistically significantly different be tween male and female horses for AA (p < .05). According to these results, some PK parameters such as Cmax, AUC, and MRT, MAA and AA concentrations have shown statistically significant differences by MT administrations.
Ionic Liquids in Analytical Chemistry: Applications and Recent Trends
(03.07.2021) Merone, Giuseppe; Targalia, Angela; Rosata, Enrica; Dovidio, Christian; Kabir, Abuzar; Ulusoy, Halil İbrahim; Savini, Fabio; Locatelli, Marcello
Background: Ionic liquids (ILs) are a unique class of compounds consisting exclusively of cations and anions that possess distinctive properties such as low volatility, high thermal stability, miscibility with water and organic solvents, electrolytic conductivity and non-flammability. Ionic liquids have been defined as "design solvents", because it is possible to modify their physical and chemical properties by appropriately choosing cations and anions, in order to meet the specific characteristics based on their potential application. Introduction: Due of their tunable nature and properties, ILs are considered as the perfect candidates for numerous applications in analytical chemistry including sample preparation, stationary phases in liquid or gas chromatography, additives in capillary electrophoresis, or in mass spectrometry for spectral and electrochemical analysis. In the last years, the number of publications regarding ILs has rapidly increased, highlighting the broad applications of these compounds in various fields of analytical chemistry. Results: This review first described the main physico-chemical characteristics of ionic liquids, and subsequently reported the various applications in different subdisciplines of analytical chemistry, including the extraction procedure and separation techniques. Furthermore, in each paragraph the most recent applications of ionic liquids in the food, environmental, biological, etc. fields have been described. Conclusion: Overall, the topic discussed highlights the key role of ionic liquids in analytical chemistry, giving hints for their future applications in chemistry but also in biology and medicine.
Investigating the effects of the Rho-kinase enzyme inhibitors AS1892802 and fasudil hydrochloride on the contractions of isolated pregnant rat myometrium
(ELSEVIER SCIENCE BV, 2016) Ergul, Merve; Turgut, Nergiz H.; Sarac, Bulent; Altun, Ahmet; Yildirim, Sahin; Bagcivan, Ihsan
Objectives: Rho-kinases (ROCKs), are one of the dynamic structures of the actin cytoskeleton and they mediate different biological processes, including regulation of calcium sensitivity of smooth muscle contraction. The activation of Rho A/ROCK system is thought to be effective on the termination time of the pregnancy process. The aim of this study, was to investigate in vitro effects of the ROCK enzyme inhibitors, clinically available fasudil hydrochloride, and a new promising inhibitor AS1892802, on the contractions of isolated pregnant rat myometrium. Study design: Term pregnant Wistar albino rats (n = 12), weighing 200-220 g, were used in this study. Myometrial tissues obtained from rats were dissected into four full-thickness longitudinal muscle strips and then myometrial tension was recorded isometrically. The inhibitory effects of cumulative concentrations of AS1892802 and of fasudil hydrochloride in the presence and absence of ODQ (guanylate cyclase inhibitor), L-NAME (nitric oxide synthase inhibitor) and L-NNA (endothelial nitric oxide synthase inhibitor) on oxytocin-induced myometrial contractions were measured, and values for -log10 EC50 (pD(2)) and mean maximal inhibition (E-max) were compared. Results: Both ROCK inhibitors, AS1892802 and fasudil hydrochloride starting from the concentrations of 10(-6) M reached statistical significance on contraction amplitude and frequency of myometrial strips (p < 0.05). The inhibition of the amplitude and frequency of myometrial contractions was antagonized with ODQ (10(-5) M; only amplitude), L-NAME (3 x 10(-5) M) and L-NNA (10(-5) M) (p < 0.05). Conclusion: These results suggest that fasudil hydrochloride and AS1892802 may contribute to the development of new tocolytic drugs. We conclude that AS1892802 and fasudil hydrochloride perform this inhibitory effect partially through ROCK inhibition and the NO/cGMP pathway. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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