Deniz Kibar
FEN FAKÜLTESİ
BİYOLOJİ BÖLÜMÜ GENEL BİYOLOJİ ANABİLİM DALI
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E-Postadkibar@mersin.edu.tr
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YÖK Araştırmacı No261536
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Evaluation of the effect of resveratrol on bone healing after tooth extraction in rats treated with zoledronic acid
Kucuk, Ayse Ozcan | Ak, Burak | Yılmaz, Şakir Necat | Kibar, Deniz | Gök, Ayşe Betül
This study aimed to evaluate the potential use of resveratrol on bone healing after tooth extraction in zoledronic acid-treated rats. Seventy-two Wistar rats were separated into 4 groups of 18: no drugs (control group), zoledronic acid (ZA), resveratrol (RES), zoledronic acid + resveratrol (ZA + RES). The first and second molars of each rat were extracted and nine rats from each group were sacrificed on days 14 and 28. The extraction sites and blood samples were analyzed histologically, immunohistochemically and biochemically. The epithelization, connective tissue, new bone formation in RES group was significantly higher compared to ZA and ZA + RES groups on day 28. The connective tissue in control group was significantly higher compared to ZA and ZA + RES groups on days 14 and 28. BMP-4 levels in RES group were significantly higher compared to the other groups on days 14 and 28. Serum CTX levels in ZA + RES group were significantly higher compared to control and RES groups on day 14. Serum TRACP-5b levels in ZA + RES group, were significantly higher compared to control and RES groups on day 14. TRACP-5b level of the control was significantly lower than ZA and ZA + RES groups. Although resveratrol improved new bone formation in normal rats, no significant positive effects were de...
Investigation of the anticancer of photodynamic therapy effects by using the novel Schiff base ligand palladium complexes on human breast cancer cell line
Demirbağ, Burcu | Ballı, Ebru | Orekici Temel, Gülhan | Yılmaz, Mustafa Kemal | Değirmenci, Evren | Kibar, Deniz
Chemotherapy plays a role in many cancer therapies, including breast cancer, but due to its significant side effects, alternate treatment approaches have been investigated. One such alternative is photodynamic therapy (PDT), which employs a combination of oxygen, a photosensitizer (PS), and light of a specific wavelength. Transition metal complexes and SBL have gained interest in PDT. In this study aimed to assess the potential antitumor activity and underlying mechanism of a newly synthesized Schiff base ligand (SBL)-mediated PDT on MCF-7 cells, comparing its efficacy to cisplatin. We synthesized and characterized two novel Pd-conjugated SBL compounds (complex-1 and 2). Following the treatment of MCF-7 cells with these compounds, a light-emitting diode (LED) was utilized to deliver a light dose of 14.8 J/cm2. In MCF-7 cells, we also looked at cytotoxicity, cell death rates, and ROS levels. Results indicated a significant increase in cytotoxicity (IC50:12.5 µM) (p
Investigation of the role of KATP channels in the cytotoxic effect of cypermethrin on rat-derived aortic smooth muscle cells
Söğüt, Fatma | Kibar, Deniz | Çömelekoğlu, Ülkü
We investigate role of atP sensitive potassium (KatP) channel in cytotoxic effect of cypermethrin on rataortic smooth muscle cells. cytotoxicity analysis was performed at 0, 0.1, 0.5, 10, 50, and 100 µMconcentrations of cypermethrin and the cell index (ci) was calculated. KatP currents were recorded usingpatch clamp technique for 50 and 100 µM concentrations and channel conductivity was determined byobtaining current-voltage characteristics. No cytotoxic effect was observed in the first 72 hours. at the96th hour, only at 100 µM concentration, the ci value decreased significantly compared to control groupand at 120 and 144th hours, it was observed that the ci value decreased significantly at all concentrations.currents and conductivities were significantly decreased at 50 and 100 µM concentrations. Results gaveclues that cypermethrin causes a cytotoxic effect on vascular smooth muscles and that KatP channelsmay have a role in the emergence of this effect.
Investigation of the role of K-ATP channels in the cytotoxic effect of cypermethrin on rat-derived aortic smooth muscle cells
Söğüt, Fatma | Uzun, Coşar | Kibar, Deniz | Çömelekoğlu, Ülkü
We investigate role of ATP sensitive potassium (KATP) channel in cytotoxic effect of cypermethrin on rat aortic smooth muscle cells. Cytotoxicity analysis was performed at 0, 0.1, 0.5, 10, 50, and 100 µM concentrations of cypermethrin and the cell index (CI) was calculated. KATP currents were recorded using patch clamp technique for 50 and 100 µM concentrations and channel conductivity was determined by obtaining current-voltage characteristics. No cytotoxic effect was observed in the first 72 hours. At the 96th hour, only at 100 µM concentration, the CI value decreased significantly compared to control group and at 120 and 144th hours, it was observed that the CI value decreased significantly at all concentrations. Currents and conductivities were significantly decreased at 50 and 100 µM concentrations. Results gave clues that cypermethrin causes a cytotoxic effect on vascular smooth muscles and that KATP channels may have a role in the emergence of this effect.
Cytotoxic effect of silica nanoparticles on human retinal pigment epithelial cells
Çömelekoğlu, Ülkü | Kibar, Deniz | Yıldırımcan, Saadet | Yılmaz, Şakir Necat
In recent years, the use of nanotechnology-based methods has become widespread in the treatment of ocular diseases. Silica nanoparticles (SiO2 NPs) are most common used NPs in medical field due to their physicochemical properties. SiO2 NPs can easily cross biological membranes and interact with basic biological structures, causing structural and functional changes in cells. In this study, it was aimed to investigate the dose dependent effect of SiO2 NPs on retinal pigment epithelium (RPE) in vitro using electrobiophysical, biochemical and histological methods. A commercially purchased human RPE (hARPE-19) cell line was used in this study. Cells were divided into four groups as control, 50 mg/mL SiO2, 100 mg/mL SiO2 and 150 mg/mL SiO2 groups. Cell index, apoptotic activity, cell cycle and oxidative stress markers were measured in all groups. Findings in the present study showed that SiO2 nanoparticles reduced cell proliferation, increased oxidative stress, apoptosis and arrest in the G0/G1 phase of the cell cycle as dose dependent manner in ARPE-19 cells. In conclusion, SiO2 exposure can induce cytotoxic effects in RPE cell line. The results of this study provide clues that exposure to SiO2 nanoparticles may impair visual function and reduce quality of life. However, further stud...
Determination of the effect of silica nanoparticles on TRP currents in retinal pigment epithelial cells by entropy measurement
Söğüt, Fatma | Kibar, Deniz | Yılmaz, Şakir Necat | Çömelekoğlu, Ülkü
Ion channels in cell membranes are gated, water-filled pores that allow passive transport of ions across the membrane along their electrochemical gradient. Recent studies have shown that nanoparticles can interact with ion channels and change their currents kinetics properties of the channel. In this study, we used the transient receptor potential (TRP) channel currents in retinal pigment epithelial (RPE) cells recorded by whole-cell patch clamp technique to observe the silica nanoparticle-ion channel interaction. For whole cell recordings, we clamped membrane potential to −40 mV and used a ramp of 1000 ms duration for stimulation. The ramp was increased from −140 mV to +60 mV. We used windowed scalogram entropy and compared the results with windowed scale index method. Our results indicated that the temporal change of entropy using windowed scalogram entropy method is sensitive to demonstrating the effect of silica nanoparticles on RPE cell TRP currents. Furthermore, windowed scale index can analyze the temporal fluctuations in the aperiodicity of cell membrane current signals. Our findings suggest that entropy measurement methods may be useful in the function analysis of cell ion channels.
Study and development of electrospun (TPU, PA-6) / silicone bilayer membranes for congenital diaphragmatic hernia repair
Bölgen, Nimet | Yılmaz, Şakir Necat | Kibar, Deniz
Large defects in the congenital diaphragmatic hernia (CDH) are treated by prosthetic materials, most frequently polytetrafluoroethylene (PTFE), with high complications. The purpose of this study is to develop a novel electrospun double-faced prosthesis that will minimize these surgical complications. Polyamide 6 (PA-6) and thermoplastic polyurethane (TPU) nanofibers were prepared by solution electrospinning, and room temperature vulcanized silicone (RTV) was used in electrospinning by dip-coating to develop a double-faced membrane. The results demonstrate that the duration of electrospinning and thickness of silicone layers influence the morphology of the bilayer scaffolds. Electrospun bilayer polyamide 6/silicone and thermoplastic polyurethane/silicone scaffolds are fabricated as potential substitutes for prosthetic membrane applications in this study. The morphology, topography, mechanical, and biological properties of these electrospun meshes have been reported to make adequate conclusions in in vitro studies. The morphological characterizations show two distinct layers of electrospun and silicone layer which can mimic the morphology of PTFE prosthesis. However, the mechanical results of the developed TPU/Silicone membrane demonstrate improved mechanical properties. In additio...
Pharmacological Inhibition of Mammalian Target of Rapamycin Attenuates Deoxycorticosterone Acetate Salt–Induced Hypertension and Related Pathophysiology: Regulation of Oxidative Stress, Inflammation, and Cardiovascular Hypertrophy in Male Rats
Temiz Reşitoğlu, Meryem | Sucu, Nehir | Kibar, Deniz | Yılmaz, Şakir Necat | Tunçtan, Bahar | Şahan Fırat, Seyhan
The present study aimed to explore the contribution of mammalian target of rapamycin (mTOR) in deoxycorticosterone acetate (DOCA) salt–induced hypertension and related pathophysiological changes in cardiovascular and renal tissues. DOCA salt loading resulted in an increase in systolic blood pressure, diastolic blood pressure, and mean blood pressure along with the activity of ribosomal protein S6, the effector protein of mTOR. Treatment with rapamycin, the selective inhibitor of mTOR, initiated at the fourth week of DOCA- salt administration normalized the systolic blood pressure and attenuated ribosomal protein S6 activity in the heart, aorta, and kidney. Cardiac and vascular hypertrophy, oxidative stress, and infiltration of macrophages (CD68+), the marker of inflammation, were also reduced in rapamycin-treated, DOCA-salt, hypertensive rats. In addition, renal hypertrophy and dysfunction were also reduced with rapamycin-treated hypertensive rats. Moreover, these pathophysiological changes in DOCA-salt hypertensive rats were associated with increased NADPH oxidase (NOX) activity, gp91phox (formerly NOX2) expression, ERK1/2, and p38 MAPK activities in the heart, aorta, and kidney were minimized by rapamycin. These data indicate that mTOR plays an important role in regulating bloo...
mTOR inhibition as a possible pharmacological target in the management of systemic inflammatory response and associated neuroinflammation by lipopolysaccharide challenge in rats
Temiz Reşitoğlu, Meryem | Kibar, Deniz | Yılmaz, Şakir Necat | Tunçtan, Bahar | Şahan Fırat, Seyhan
Neuroinflammation plays a critical role during sepsis triggered by microglial activation. Mammalian target of rapamycin (mTOR) has gained attraction in neuroinflammation, however, the mechanism remains unclear. Our goal was to assess the effects of mTOR inhibition by rapamycin on inflammation, microglial activation, oxidative stress, and apoptosis associated with the changes in the inhibitor-κB (IκB)-α/nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α) pathway activity following a systemic challenge with lipopolysaccharide (LPS). Rats received saline (10 mL/kg), LPS (10 mg/kg), and (or) rapamycin (1 mg/kg) intraperitoneally. Inhibition of mTOR by rapamycin blocked phosphorylated form of ribosomal protein S6, NF-κB p65 activity by increasing degradation of IκB-α in parallel with HIF-1α expression increased by LPS in the kidney, heart, lung, and brain tissues. Rapamycin attenuated the increment in the expression of tumor necrosis factor-α and interleukin-1β, the inducible nitric oxide synthase, gp91phox, and p47phox in addition to nitrite levels elicited by LPS in tissues or sera. Concomitantly, rapamycin treatment reduced microglial activation, brain expression of caspase-3, and Bcl-2-associated X protein while it increased expression of B cell lymphoma 2 induced by LP...
Ameliorative effects of paricalcitol against 1800-MHz mobile phone radiation-induced skin damage in rats
Aktaş, Savaş | Çömelekoğlu, Ülkü | Demirbağ, Burcu | Kibar, Deniz | Söğüt, Fatma | Yalın, Serap
This study aimed to evaluate the protective role of paricalcitol, a vitamin D analog, against hazardous effects of 1800-MHz radiofrequency (RF) radiation on the skin of male Wistar albino rats exposed one h/day for 4 weeks. The maximum specific absorption rate was calculated as 0.0042 W/kg. Superoxide dismutase and catalase activity, collagen bundle thickness, breaking force, energy, and stress were decreased, while malondialdehyde level and mast cell number were increased. The exposure to 1800-MHz RF radiation caused a reduction in skin biomechanical quality through oxidative stress and mast cell activation. The administration of paricalcitol caused a significant improvement.
Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats
Güzel, Sevda | Uçkun, Zuhal | Canacankatan, Necmiye | Antmen, Ş. Efsun | Kibar, Deniz | Coşkun Yılmaz, Banu
Silymarin (SLY), a flavonoid complex isolated from the seeds of Silybum marianum (Asteraceae), has antioxidant, anti-apoptotic, anti-inflammatory, and anti-lipid peroxidative effects. Vancomycin (VA), used for treating serious infections, has been associated with nephrotoxicity, which limits its use. Therefore, this study aimed to investigate the potential renoprotective effects of SLY on VA-induced nephrotoxicity using renal, apoptotic (caspase-3, caspase-8, and caspase-9 enzyme activities), and oxidative stress [nitric oxide (NO) and malondialdehyde (MDA)] markers; serum blood urea nitrogen (BUN) and creatinine levels; and histopathological examination. A total of 49 male Wistar albino rats were used (n = 7): control [saline, intraperitoneally (i.p.)], dimethyl sulfoxide (i.p.), VA [400 mg/(kg-day), i.p.], SLY100 [100 mg/(kg-day), i.p.], VA + SLY50 [50 mg/(kg-day), i.p.], VA + SLY100 [100 mg/(kg-day), i.p.], and VA + SLY200 [200 mg/(kg-day), i.p.]. SLY was administered once daily for 8 days. One day after the first treatment of SLY, VA administration was started and continued for 7 days. The levels of serum creatinine and BUN were evaluated using ELISA, caspase enzyme activities and levels of MDA and NO in the kidney tissues were evaluated by the colorimetric methods. The serum...
The ameliorating effect of silymarin against vancomycin-induced apoptosis and inflammation in rat liver
Güzel Kara, Sevda | Uçkun Şahinoğulları, Zuhal | Canacankatan, Necmiye | Antmen, Ş. Efsun | Kibar, Deniz
Silymarin (SL), a flavonolignan complex isolated from seeds of Silybum marianum (Asteraceae), is known for its hepatoprotective, anti-apoptotic, anti-inflammatory, and antioxidant activities. A glycopeptide antibiotic, Vancomycin (VA) which is used for the treatment of serious infections caused by multi-resistant Gram-positive microorganisms has been clinically used for a long time. The aim of the present study was to evaluate potential therapeutic efficiency of SL against VA-induced apoptosis and inflammation using apoptotic (caspase-3, -8, and, -9) enzyme activities) and inflammatory (Tumor necrosis factor-alpha (TNF-α)) markers, and histopathological examinations in rat liver. A total of 49 male Wistar albino rats was divided into 7 groups including control (saline, intraperitoneally (i.p.)), Dimethyl sulfoxide (i.p.), VA (400 mg/kg/day, i.p.), SL100 (100 mg/kg/day, i.p.), VA+SL50 (50 mg/kg/day, i.p.), VA+SL100 (100 mg/kg/day, i.p.), and VA+SL200 (200 mg/kg/day, i.p.). SL was administered once a daily for 8 days. One day after the first treatment of SL, VA administration was started and continued for 7 days. Hepatic TNF-α levels were evaluated by ELISA and hepatic caspase activities were evaluated according to the colorimetric method. Significantly increased caspase activities...
Effect of axitinib on inflammation in experimental corneal neovascularization model in rats
Canacankatan, Necmiye | Dinç, Erdem | Kibar, Deniz | Antmen, Ş. Efsun | Yılmaz, Banu COŞKUN | Taşdelen, Bahar
Purpose: This study investigated the antiinflammatory efficacy of topical application of a selective tyrosine kinase receptor inhibitor (TKI), Axitinib in experimental corneal neovascularization (CNV) model in rats. Vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2 and VEGFR3 were evaluated as angiogenic markers, nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNFα) and cyclooxygenase-2 (COX2) were determined as inflammatory markers and also histopathological evaluations were carried out. Materials and Methods: Experimental CNV model was established by silver nitrate cauterization in right eye. 6 groups were included as Control; CNV; CNV+DMSO; CNV+0.04% Axitinib; CNV+0.08% Axitinib and CNV+0.24% Axitinib. The corneas were collected and VEGFR1, VEGFR2, VEGFR3, NF-κB, TNFα and COX2 were measured by ELISA. Results: Axitinib, significantly reduced corneal VEGFR1 and VEGFR2 compared to CNV. The most efficiency of Axitinib treatment was confirmed on VEGFR2 and especially with 0.04% dose. Increased NF-κB and TNFα level were reduced by 0.04% Axitinib treatment compared to CNV and CNV+DMSO. Conclusion: Axitinib may be suggested as a promising anti-inflammatory agent in CNV by suppressing corneal VEGFR1, VEGFR2, NF-κB and TNFα, beside improving the histological p...
Potential protective effects of naringenin against vancomycin-induced nephrotoxicity via reduction on apoptotic and oxidative stress markers in rats
Uçkun, Zuhal | Güzel, Sevda | Canacankatan, Necmiye | Kibar, Deniz | Coşkun Yılmaz, Banu
Vancomycin (VCM), a glycopeptide antibiotic, is a drug widely used in severe infections. However, VCM induce notable nephrotoxic side effects. Naringenin (NAR) is a natural of flavonoid and are known as strongly antioxidant, nefroprotective, antiapoptotic, and anti-inflammatory. The purpose of this study was to determine the potential protective effects of NAR against VCM-induced nephrotoxicity by measuring apoptotic and oxidative stress markers and evaluating histopathological alterations in rats. For this purpose, we used male Wistar albino rats that divided into seven groups: (i) Control [saline, intraperitoneally (i.p.)], (ii) carboxymethyl cellulose (0.5% CMC, orally), (iii) VCM (400 mg/kg, i.p.), (iv) NAR100 (100 mg/kg, orally), (v) VCM + NAR25 (25 mg/kg, orally), (vi) VCM + NAR50 (50 mg/kg, orally), and (vii) VCM + NAR100 (100 mg/kg, orally) groups. VCM administration was started one day after the first treatment of NAR and continued across 7-day. Caspase-3, -8, and-9 activities and malondialdehyde (MDA) and nitric oxide (NO) levels were measured by colorimetric methods in the kidney tissues, creatinine, and blood urea nitrogen (BUN) levels were analyzed based on ELISA in serum. Caspase-3 and -8 activities, NO levels, serum creatinine and BUN levels were significantly high...
N -Acetylcysteine-induced vasodilatation is modulated by K ATP channels, Na /K -ATPase activity and intracellular calcium concentration: An in vitro study
Çömelekoğlu, Ülkü | Sucu, Nehir | Yalın, Ali Erdinç | Yılmaz, Şakir Necat | Yalın, Serap | Söğüt, Fatma | Kibar, Kezban | Akkapulu, Merih
Background In this study, we aimed to investigate the role of ATP-sensitive potassium (KATP) channel, Na+/K+-ATPase activity, and intracellular calcium levels on the vasodilatory effect of N-acetylcysteine (NAC) in thoracic aorta by using electrophysiological and molecular techniques. Methods Rat thoracic aorta ring preparations and cultured thoracic aorta cells were divided into four groups as control, 2 mM NAC, 5 mM NAC, and 10 mM NAC. Thoracic aorta rings were isolated from rats for measurements of relaxation responses and Na+/K+-ATPase activity. In the cultured thoracic aorta cells, we measured the currents of KATP channel, the concentration of intracellular calcium and mRNA expression level of KATP channel subunits (KCNJ8, KCNJ11, ABCC8 and ABCC9). Results The relaxation rate significantly increased in all NAC groups compared to control. Similarly, Na+/K+- ATPase activity also significantly decreased in NAC groups. Outward KATP channel current significantly increased in all NAC groups compared to the control group. Intracellular calcium concentration decreased significantly in all groups with compared control. mRNA expression level of ABCC8 subunit significantly increased in all NAC groups compared to the control group. Pearson correlation analysis showed that relaxatio...