Person: ŞENER, AZİZE
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ŞENER
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AZİZE
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Publication Open Access Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents(MDPI, 2013-03-21) ŞENER, AZİZE; Kucukguzel, S. Guniz; Coskun, Inci; Aydin, Sevil; Aktay, Goknur; Gursoy, Sule; Cevik, Ozge; Ozakpinar, Ozlem Bingol; Ozsavci, Derya; Sener, Azize; Kaushik-Basu, Neerja; Basu, Amartya; Talele, Tanaji T.A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamides 2a-e were synthesized by the addition of ethyl alpha-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)- 1H-pyrazol-1-yl] benzene sulfonamides 1a-e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)- 3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent.Publication Metadata only Characterization of platelet gamma glutamyltransferase and its alteration in cases of atherosclerosis(LIPPINCOTT-RAVEN PUBL, 1995) ŞENER, AZİZE; Yardimci, T; Yaman, A; Ulutin, OAmong the various functional and biochemical alterations in the platelets of cases of atherosclerosis, the membrane alterations occupy an important place. The platelet intrinsic membrane protein gamma glutamyltransferase (GGT), which is involved in glutathione metabolism, has shown decreased activity in cases of atherosclerosis. To add new insights into the pathogenesis of atherosclerosis, GGT is characterized and correlated with other alterations. Triton X-100 solubilized membrane fractions of frozen and thawed platelets of atherosclerotic and normal subjects had 18.66 +/- 2.86 mU/10(9) platelets and 35.67 +/- 3.01 mU/10(9) platelets, respectively. The K-m values were the same, 2.08 mmol/L for gamma glutamyl-p-nitroanilide and 5.87 mmol/L for glycylglycine. The V-max values were reduced from 100 mU/10(9) platelets to 41.66 mU/10(9) platelets for gamma glutamyl-p-nitroanilide and from 45.45 mU/10(9) platelets to 38.46 mU/10(9) platelets for glycylglycine. Optimum pH of GGT activity was 8.2, and optimum temperature was 37 degrees C. It had thermal stability with a 64% relative activity at 56 degrees C for 30 min. Serine against berate was detected as the competitive inhibitor and bromcresol green as the noncompetitive inhibitor. In vivo administration of the antithrombotic drug defibrotide increased the platelet GGT levels to those of normals, from 14.72 +/- 7.27 mU/10(9) platelets to 31.80 +/- 12.21 mU/10(9) platelets in 2 hs. Cholesterol, high-density lipoprotein cholesterol in the membrane fractions, and platelet glutathione levels were unaltered. The lipid peroxidation (membrane malondialdehyde) level was increased, and glucose and histidine active transport systems were impaired in atherosclerotics. All of these changes are discussed in relation to GGT.Publication Metadata only Exogenous L-Arginine and HDL Can Alter LDL and ox-LDL-Mediated Platelet Activation: Using Platelet P-Selectin Receptor Numbers(SAGE PUBLICATIONS INC, 2011) ŞENER, AZİZE; Sener, Azize; Enc, Elif; Ozsavci, Derya; Vanizor-Kural, Birgul; Yanikkaya-Demirel, Gulderen; Oba, Rabia; Uras, Fikriye; Demir, MuzafferThe aim of this study is to investigate the effects of exogenous L-arginine and HDL on LDL and oxidized LDL (ox-LDL)-mediated platelet activation. Adenosine diphosphate (ADP)-activated platelets have been incubated with lipoproteins with or without L-arginine. P-selectin receptor numbers per platelet have been measured by flow cytometry. After incubation with only L-arginine (without lipoproteins), platelet nitric oxide (NO) levels and P-selectin receptor numbers significantly increased compared to the controls (P < .05). After incubation with LDL or ox-LDL, receptor numbers of P-selectin significantly increased (P < .001). However, P-selectin receptor numbers in platelets treated with L-arginine + LDL or L-arginine + ox-LDL decreased compared to the levels in platelets treated with only LDL or ox-LDL (P < .01, P < .001, respectively). Addition of HDL to L-arginine + ox-LDL caused significant reduction in P-selectin receptor numbers as in the control values (P < .001). We have concluded that L-arginine causes enhanced platelet NO levels and blocks the effects of LDL or ox-LDL on platelet P-selectin receptor numbers and HDL also strengthens this effect of L-arginine.Publication Metadata only Synthesis of Diflunisal Thiazolidinones as Anticancer Agents(BENTHAM SCIENCE PUBL LTD, 2016) ŞENER, AZİZE; Senkardes, Sevil; Ozakpinar, Ozlem B.; Ozsavci, Derya; Sener, Azize; Cevik, Ozge; Kucukguzel, S. GunizA series of diflunisal 4-thiazolidinones were synthesized. Some selected compounds were determined at one dose towards the full panel of 60 human cancer cell lines by National Cancer Institute. 2',4'-Difluoro-4-hydroxy-N-[4-oxo-2-(thiophen-2-yl)-1,3-thiazolidin-3-yl]biphenyl-3-carboxamide (4a) demonstrated the most marked effect on K-562 cancer cell line with 58.59 % growth inhibition at 10 mu M. Compound 4a was evaluated in vitro using the MTT colorimetric method against human leukemia cell line K-562 and mouse embryonic fibroblasts cell line NIH-3T3 at different doses for cell viability and growth inhibition. Compound 4a exhibited anticancer activity with IC50 value of 5.2 mu M against K-562 cells and did not display cytotoxicity towards NIH-3T3 cells compared with diflunisal. In addition, this compound could be an interesting prototype as an antiproliferative agent.Publication Open Access The antioxidant, anti-inflammatory and antiplatelet effects of Ribes rubrum L. fruit extract in the diabetic rats(2022-03-01) ŞENER, AZİZE; ŞEKERLER, TURGUT; ŞEN, ALİ; Gülmez G., Şen A., Şekerler T., Algül F. K., Çilingir-Kaya Ö. T., Şener A.AbstractThe prothrombotic and inflammatory state plays a significant role in the occurrence of cardiovascular complications in type 2 diabetes mellitus. In this study, the antidiabetic, anti-inflammatory, and antiplatelet potentials of the extracts obtained fromRibes rubrumwere investigated. The antidiabetic, anti-inflammatory, and antioxidant activities of the ethanol and water extracts ofR. rubrumwere evaluated by in vitro methods. The total phenolic and flavonoid contents were also determined. The experimental diabetes model in rats was induced with streptozotocin (STZ). After hyperglycemia occurred, the ethanol extracts ofR. rubrum(RRE, at 100mg/kg and 500mg/kg doses) were administered to the treatment groups for 14days. Blood glucose, lipid profile, plasma, and pancreas tumor necrosis factor-α (TNF-α) levels were determined and compared at the end of the experiments. P-selectin levels and mitochondrial membrane polarization (MMP) of platelets were also measured. In vitro study, the RRE showed potent anti-inflammatory activity. Administration of RRE (at 100mg/kg doses) to diabetic rats lowered blood glucose level insignificantly. The results showed that there was an increment in levels of TNF-α in plasma and pancreas tissue of the diabetic group compared to the control group.R. rubrumextract regulated and normalized their levels in plasma and pancreatic tissue. RRE at both doses significantly decreased platelet P-selectin levels and prevented STZ-induced loss of MMP in platelets. The results of current research indicate that RRE extract has potent anti-platelet and anti-inflammatory effects and may be beneficial in preventing diabetic complications.Practical applicationsHyperglycemia causes dyslipidemia, advanced oxidative stress, platelet activation, and inflammation in diabetes mellitus. Plants with various medicinal properties are of worldwide interest for the treatment of diseases due to their biological activities. In this study, the antidiabetic, anti-inflammatory, and antioxidant effects of extracts ofRibes rubrum(%100 ethanol, 50% ethanol, water) were evaluated by in vitro and in vivo methods. The diabetes model was induced with streptozotocin (STZ). The rats were divided into control, diabetic control,R. rubrum-100mg/kg, andR. rubrum-500mg/kg doses groups. Blood glucose levels, tumor necrosis factor-α (TNF-α), platelet P-selectin levels, mitochondrial membrane polarization of platelets were examined. The present study has shown thatR. rubrumhas anti-inflammatory and antiplatelet activity.R. rubrummay be beneficial in the prevention and treatment of DM complications due to its anti-inflammatory and antithrombotic effects.Publication Open Access Publication Open Access Demir (III) varliginda trombosit gamaglutamil transferazinin pro-oksidan etkisi(2011-01-01) ŞENER, AZİZEPublication Metadata only Effect of Horse-chestnut seed extract on matrix metalloproteinase-1 and-9 during diabetic wound healing(WILEY, 2019) ŞEN, ALİ; Aksoy, Halil; Cevik, Ozge; Sen, Ali; Goger, Fatih; Sekerler, Turgut; Sener, AzizeThe effects of aqueous-ethanol extract of Horse chestnut (HCE) on MMP-1 and MMP-9 expressions during cutaneous wound healing in diabetic rats were investigated in this study. The expressions of MMP-1 and MMP-9, wound closure, myeloperoxidase (MPO) activity, hydroxyproline, and malondialdehyde (MDA) levels in wound tissue were measured. Quercetin glucuronide in HCE was identified as main compound using a LC-MS/MS. The hydroxyproline level was significantly increased in the treated group versus control after the 3rd and 7th days (p < 0.05). The MDA level and MPO activity were significantly lower in the treatment group (p < 0.05). MMP-1 gene expression level in treated rats was increased in the 7th day while it was reduced in 14th day. MMP-9 gene expression level in treated rats was decreased in 7th, and 14th days compared to control (p < 0.05). These results show that HCE accelerated the cutaneous wound-healing process in diabetic rats via MMP-1 and MMP-9 regulation.Publication Metadata only Evaluation of biochemical parameters inRubus tereticaulistreated rats and its implications in wound healing(SPRINGER, 2020) ŞEN, ALİ; Aksoy, Halil; Demirbag, Caglar; Sen, Ali; Sekerler, Turgut; Ozakpinar, Ozlem; Sener, Azize; Ahmad, Sarfraz; Tetik, SerminWe evaluated the effects ofRubus tereticaulisin healing process by determining the total carbonyl content, collagen synthesis, and total protein level on rat wounded tissues. Wounds were performed in the back of 54 Wistar rats, using a biopsy punch instrument with 0.6 mm in diameter. Rats were randomly divided into three groups: (i) un-treatment wounds group served as controls, (ii) Madecassol (R) used as positive control group, and (iii) the application of topical cream ofR. tereticaulisserved as treatment group of wound healing. The animals were killed at the end of experiment under anesthesia with ketamine, and tissue samples were collected for the evaluation at three times intervals (3rd, 7th, and 14th day). The wounded areas were analyzed for total carbonyl content, collagen, and total protein levels by HPLC, ELISA, and spectrophotometric methods, respectively. Total carbonyl content in the treatment group was significantly lower in comparison with control group on 3rd day (2.839 +/- 0.438 vs. 3.216 +/- 0.216 nmol carbonyl/mol protein;p < 0.5) and 14th days (4.222 +/- 0.128 vs. 4.784 +/- 0.077 nmol carbonyl/mol protein;p < 0.05), respectively. New collagen formation on the wound sites after the initial injury was noted in the treated and positive control groups (5.310 +/- 0.331 vs. 5.164 +/- 0.377 mg collagen/g wet tissue) at the 3rd day than control group (2.180 +/- 0.718 mg collagen/g wet tissue,p < 0.01), and in treated and positive control groups at 7th day (9.654 +/- 0.201, 9.053 +/- 1.062 mg collagen/g wet tissue,p < 0.01); and in treated and positive control groups at 14th day (8.469 +/- 0.236, 5.631 +/- 0.531 mg collagen/g wet tissue, respectively;p < 0.05) in comparison with the control group. Total protein level of samples did not change significantly between the groups. Thus, application ofR. tereticaulisameliorated the wound healing process in rats as it facilitated collagen formation through healing of the wound. Evaluating total carbonyl content by HPLC could be useful as an advance procedure for quantification of healing.Publication Open Access The Effect of Algan Hemostatic Agent (AHA) on Wound Healing(MARMARA UNIV, INST HEALTH SCIENCES, 2020-09-04) ŞEN, ALİ; Aksoy, Halil; Sener, Azize; Akakin, Dilek; Sen, Ali; Ozakpinar, Ozlem Bingol; Ozcan, Sinemcan; Simsek, Ahmet Kaan; Sekerler, Turgut; Guzel, Sevket Ergun; Midi, AhmetObjective: The Algan Hemostatic Agent (AHA) is a novel herbal originated blood stopper. The aim of this study is to investigate the effect of AHA on wound healing on excisional wound model in rats. Methods: In this study, 54 adult Wistar albino rats were used. Rats were divided into 3 groups (saline, Madecassol (R) and AHA). Each group was then divided into 3 subgroups as the 3rd, 7th and 14th days. Two wounds were created in the dorsal thoracic region of the rats. One of the lesions was used for histopathological examinations and the other for hydroxyproline measurement. In order to evaluate the wound healing, wound area were measured during the whole treatment period and animals were sacrificed at the end of the 3rd, 7th and 14th days and tissue samples were taken for the determination of hydroxyproline levels. Results: AHA treatment did not cause significant difference in hydroxyproline level on days 3, 7, 14. The contraction percentage of wound area was higher in the AHA group on day 7 than that of the control group. However, the difference was not statistically significant (p>0.05). On days 3 and 14, no significant difference was detected in the contraction percentage of wound area between the control and the AHA groups. AHA and Madecassol (R) results of epidermis regeneration on the 14th day, neutrophil infiltration on the 7th day and edema on the 3rd, 7th and 14th days were different in terms of histopathological parameters compared to the control group. Conclusion: Despite good histological findings, AHA did not significantly accelerate wound healing, but did not adversely affect wound healing as well.
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