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CABADAK, HÜLYA

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CABADAK

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HÜLYA

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Now showing 1 - 10 of 26
  • Publication
    The effect of metformin on ethanol- and indomethacininduced gastric ulcers in rats
    (2022-09-01) YÜKSEL, MERAL; ERCAN, FERİHA; CABADAK, HÜLYA; AYDIN OMAY, BANU; İpek B. E. , YÜKSEL M., Cumbul A., ERCAN F., CABADAK H., AYDIN OMAY B., Alican İ.
    BACKGROUND: Previous studies found metformin as an effective agent to suppress oxidative stress, inflammation, and apoptosis in various inflammatory diseases. The present study investigated the effect of metformin against 2 experimental gastric injury models in rats, using macroscopical, histopathological, biochemical, and immunostaining studies. METHODS: After 24 hours of fasting, male Sprague-Dawley rats (280-400 g) (n = 8 per group) received indomethacin (80 mg/kg; indo ulcer group) or absolute ethanol (5 mL/kg; ethanol ulcer group) or vehicle orally by gavage. Metformin (500 mg/kg) was given orally for 3 days prior to indomethacin or ethanol challenge. Ranitidine (50 mg/kg) was given orally for 3 days before indomethacin or ethanol administration as a positive control. On day 3, the animals were euthanized 6 hours after indo or 1 hour after ethanol challenge. Gastric samples were used for macroscopic scoring, histopathological examinations, and biochemical assays. Trunk blood was collected for the assessment of interleukin-1β level. RESULTS: In both ethanol ulcer and indo ulcer groups, metformin decreased the extent of gastric lesions macroscopically and microscopically, improved the high chemiluminescence levels, and the percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with untreated ulcer groups. Gastric blood flow analysis revealed significant increases in both metformin-treated ulcer groups compared to untreated ulcer groups. CONCLUSION: The findings of the present work demonstrated the gastroprotective effect of metformin against the development of gastric mucosal lesions induced by ethanol and indomethacin in non-diabetic, normoglycemic rats via its antioxidant and anti-apoptotic properties and partly from its ability to restore blood flow.
  • PublicationOpen Access
    The behavioral and neurochemical effects of methylprednisolone or metyrapone in a post-traumatic stress disorder rat model
    (KARE PUBL, 2019) AYDIN OMAY, BANU; Tanriverdi, Ayse Melek; Aydin, Banu; Bebitoglu, Berna Terzioglu; Cabadak, Hulya; Goren, M. Zafer
    OBJECTIVE: Mechanisms contributing to the post-traumatic stress disorder (PTSD) that involve several physiological sys- tems, and the activation of the hypothalamic-pituitary-adrenal axis (HPA) is one of the most known systems in the PTSD pathophysiology. The present study investigates the potential effects of methylprednisolone, metyrapone and their association with the noradrenergic system within the rostral pons, a region containing the locus coeruleus (LC) in a rat model of PTSD induced with predator scent. METHODS: In this study, Sprague-Dawley rats were exposed to the stress by exposure to the scent of dirty cat litter, which is a natural stressor of a predator. One week later, the rats were re-exposed to a situational reminder (clean cat litter). The rats were treated using either methylprednisolone, metyrapone or physiological saline before exposure to a situational reminder (n=8 in each group). Noradrenaline (NA) levels in the rostral pons homogenates were analysed using ELISA. RESULTS: The anxiety indices of the rats exposed to the trauma were found to be significantly higher than the anxiety indices of the control rats. Metyrapone produced a significant increase in the anxiety indices of the non-stressed rats, and methylprednisolone did not produce a change in the anxiety indices of the non-stressed rats. Methylprednisolone treatment suppressed the anxiety in the stressed rats. Metyrapone treatment increased the anxiety indices in the stressed rats but still being lower than that of the saline-treated stressed rats. Significant decrease in the freezing time was observed following the methylprednisolone treatment both in the stressed and non-stressed rats. NA content in the rostral pons of the stressed rats was significantly higher than that of the non-stressed rats. Methylprednisolone or metyrapone treatments decreased the NA content in the non-stressed rats as compared to the saline treatment. However, these decreases were not significant. CONCLUSION: In this study, findings suggest that stress may give rise to endocrine, autonomic and behavioural responses. The anxiety indices and NA levels in the rostral pons increased with the traumatic event. The methylprednisolone treatment may suppress anxiety through interactions between the LC and the HPA axis.
  • Publication
    Role of cholinergic agents in proliferation and caspase activity of hemin-induced erythroid differentiated K562 cells
    (TAYLOR & FRANCIS LTD, 2020) AYDIN OMAY, BANU; Cabadak, Hulya; Aydin, Banu
    Background: Muscarinic receptors have many functions in the cells and tissues. Acetylcholine (ACh) plays an important role in cellular physiology. ACh also acts at the different parts of the central nervous system and nonneuronal cells. Cholinergic receptors also have different functions in many cell types and tissues. Caspases (cysteine aspartic proteases and cysteine aspartases) are cysteine dependent aspartate-specific proteases. They are an important role in necrosis and cell death and inflammation signaling pathways. They are also the primary mediators of apoptosis. During apoptosis, different caspase types participate in different functions. We have previously shown that carbachol (CCh) inhibits K562 cell proliferation. This study was performed to investigate the anti-tumor efficacy of cholinergic drugs in hemin-induced erythroid differentiated K562 cells. The aim of this study was to address the mechanism of cholinergic drugs on hemin-induced erythroid differentiated K562 cell proliferation and caspase activities. We detected M-3 muscarinic receptor expression in erythroid differentiated K562 cell line. Methods: K562 cells were differentiated with hemin (50 mu M). The expression of the M-3 muscarinic receptor was detected by the western blotting technique. Erythroid differentiated K562 cells treated with CCh (100 mu M). After 24 and 48 h, cells were counted by BrdU cell proliferation kit. Caspase 3,8, and 9 activities were measured by enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions. Results: Erythroid differentiated K562 cell proliferation was not significantly increased after CCh treatment. In the meantime, caspases 8 and 9 activities in erythroid differentiated K562 cell line was significantly higher than undifferentiated K562 cells (p < .05).
  • Publication
    D-Cycloserine acts via increasing the GluN1 protein expressions in the frontal cortex and decreases the avoidance and risk assessment behaviors in a rat traumatic stress model
    (ELSEVIER SCIENCE BV, 2015) CABADAK, HÜLYA; Saridogan, Gokce Elif; Aykac, Asli; Cabadak, Hulya; Cerit, Cem; Caliskan, Mecit; Goren, M. Zafer
    D-cycloserine (DCS), an FDA approved anti-tuberculosis drug has extensively been studied for its cognitive enhancer effects in psychiatric disorders. DCS may enhance the effects of fear extinction trainings in animals during exposure therapy and hence we investigated the effects of DCS on distinct behavioral parameters in a predator odor stress model and tested the optimal duration for repeated daily administrations of the agent. Cat fur odor blocks were used to produce stress and avoidance and risk assessment behavioral parameters were used where DCS or saline were used as treatments in adjunct to extinction trainings. We observed that DCS facilitated extinction training by providing further extinction of avoidance responses, risk assessment behaviors and increased the contact with the cue in a setting where DCS was administered before extinction trainings for 3 days without producing a significant tolerance. In amygdala and hippocampus, GluN1 protein expressions decreased 72 h after the fear conditioning in the traumatic stress group suggesting a possible down-regulation of NMDARs. We observed that extinction learning increased GluN1 proteins both in the amygdaloid complex and the dorsal hippocampus of the rats receiving extinction training or extinction training with DCS. Our findings also indicate that DCS with extinction training increased GluN1 protein levels in the frontal cortex. We may suggest that action of DCS relies on enhancement of the consolidation of fear extinction in the frontal cortex. (C) 2015 Elsevier B.V. All rights reserved.
  • Publication
    Investigation of the Association Between Dopamine D1 Receptor Gene Polymorphisms and Essential Hypertension in a Group of Turkish Subjects
    (INFORMA HEALTHCARE, 2011) FAK, ALİ SERDAR; Orun, Oya; Nacar, Cevdet; Cabadak, Hulya; Tiber, Pinar Mega; Dogan, Yuksel; Guneysel, Ozlem; Fak, Ali Serdar; Kan, Beki
    Dopamine has been shown to influence blood pressure by regulating renal sodium excretion through direct interaction with the dopamine receptors, especially with the Dopamine D1 receptor (DRD1). To better understand the role of polymorphisms in those effects, we investigated the association between two polymorphic sites in the DRD1 promoter region (A-48G, G-94A) and essential hypertension in the Turkish population. The DRD1 variants were genotyped by restriction fragment length polymorphism (RFLP) analysis. A total of 205 unrelated individuals were enrolled in the study. We found that genotype distributions and allele frequencies of the control and hypertensive subjects were very similar and did not show any significant difference with respect to blood pressure (BP) and hypertension. Contribution of the gene variances in BP or hypertension by sex differences and dependence on body mass index (BMI) were also evaluated. Distribution of genotypes and allele frequencies were found to be in line with previous reports. However, increments detected in hypertensive subjects were far from being statistically significant.
  • Publication
    Contribution of M-1 and M-2 muscarinic receptor subtypes to convulsions in fasted mice treated with scopolamine and given food
    (ELSEVIER SCIENCE BV, 2019) AYDIN OMAY, BANU; Bacanak, Merve Saygi; Aydin, Banu; Cabadak, Hulya; Nurten, Asiye; Goren, Mehmet Zafer; Enginar, Nurhan
    Treatment of fasted mice and rats with the nonselective muscarinic antagonist, scopolamine or atropine, causes convulsions after food intake. This study evaluated the effect of fasting on the expression of M-1 and M-2 muscarinic receptors in the brain regions, the relationship between receptor expression and seizure stages, and the muscarinic receptor subtype which plays a role in the occurrence of convulsions. Mice were grouped as allowed to eat ad lib (fed) and deprived of food for 24 h (fasted). Fasted animals developed convulsions after being treated with scopolamine (60%) or the selective M-1 receptor antagonist pirenzepine (10 mg/kg; 20% and 60 mg/kg; 70%) and given food. Fasting increased expression of M-1 receptors in the frontal cortex and M-2 receptors in the hippocampus, but produced no change in the expression of both receptors in the amygdaloid complex. Food intake after fasting decreased M-1 receptor expression in the frontal cortex and M-1 and M-2 receptor expression in the hippocampus. Seizure severity was uncorrelated with muscarinic receptor expression in the brain regions. Taken together, these findings provide evidence for the role of M-1 muscarinic receptor antagonism and fasting-induced increases in M-1 and M-2 expression possible underlying mechanism in the occurrence of convulsions in fasted animals.
  • Publication
    Evidence for the presence of muscarinic M-2 and M-4 receptors in guinea-pig gallbladder smooth muscle
    (WILEY, 1998) KARAALP, ATİLA; Oktay, S; Cabadak, H; Iskender, E; Goren, Z; Caliskan, E; Orun, O; Aslan, N; Karaalp, A; Tolun, A; Ulusoy, NB; Levey, AI; El-Fakahany, EE; Kan, B
    1 The affinities of 10 selective muscarinic receptor antagonists against [H-3]-quinuclidinyl benzilate (QNB) binding were determined to characterize the muscarinic receptors present in guinea-pig gallbladder smooth muscle. The highest correlation was obtained for the comparison between the pK(i) values for the gallbladder smooth muscle and M-2 sites. Pirenzepine revealed two binding sites with affinities indicating the presence of muscarinic M-2 receptors in abundance and a minor population of an additional site(s). 2 Carbachol produced gallbladder contractions, stimulated phosphoinositide (PI) hydrolysis and inhibited cAMP formation concentration-dependently with pD(2) values of 6.12 +/- 0.11, 5.18 +/- 0.33 and 7.19 +/- 0.15, respectively. 3 Pirenzepine, 4-DAMP, HHSiD, pF-HHSiD, AF-DX 116, methoctramine, AQ-RA 741, guanylpirenzepine and AF-DX 384 showed competitive antagonism against carbachol-induced gallbladder contractions. There was no correlation between the pA(2) values for the gallbladder and pK(i) values for the M-2 sites, whereas significant correlations were found for the M-1, M-3 and M-4 sites, the best correlation being between the pA(2) values for the gallbladder and M-4 subtypes. 4 Finally, the presence of both m(2) and m(4) receptor proteins were demonstrated by Western blot analysis. It is concluded that guinea-pig gallbladder smooth muscle has both muscarinic M-2 and M-4 receptors, which are coupled to adenylate cyclase inhibition and PI hydrolysis. 5 Although it seems likely that Mt receptors do not play a primary role in carbachol-induced guinea-pig gallbladder contraction, the characterization of the muscarinic subtypes which mediate these contractile responses needs further evidence.
  • Publication
    M-2, M-3, and M-4 muscarinic receptors are expressed in the guinea pig gallbladder
    (TAYLOR & FRANCIS LTD, 2009) CABADAK, HÜLYA; Cabadak, Hulya; Cuadra, Adolfo E.; El-Fakahany, Esam E.; Kan, Beki
    Aim: The identity of muscarinic acetylcholine receptors (mAchR) involved in cholinergic-mediated contraction of the guinea pig gallbladder has been a matter of debate. Different groups have suggested the involvement of M-1, M-2, M-3, or M-4 receptor subtypes in the contraction of this tissue. The objective of this study was to identify the mAchR subtypes expressed in the guinea pig gallbladder by RT-PCR. Methods: Total RNA prepared from frozen guinea pig gallbladder tissue was amplified by using specific primers for the M-1-M-4 receptor subtypes. Results: M-2, M-3, and M-4 transcripts were detected in the following rank order: M-4 > M-2 > M-3. We were unable to demonstrate the expression of the M, receptor subtype in this tissue. Conclusions: Our results are in agreement with our previous binding and functional data.
  • Publication
    Muscarinic receptor-mediated nitric oxide release in a K562 erythroleukaemia cell line
    (2009) AYDIN OMAY, BANU; Cabadak H., Küçükibrahimoǧlu E., Aydin B., Kan B., Gören M.Z.
    1 In the present study we have investigated the expression of muscarinic receptors in K562 erythroleukaemic cells and the effects of muscarinic agonist and antagonists on extracellular citrulline levels in these cells, as a marker of nitric oxide (NO) generation. 2 Muscarinic acetylcholine receptors (M 1-M5) play key roles in regulating many diverse physiological processes. Recent studies suggest that muscarinic receptors mediate some cellular events in haematopoietic cells. Multiple subtypes of muscarinic receptors are expressed in different human cells. NO, a free radical and a signaling molecule, is involved in the regulation of many physiological functions and derived from certain nitric oxide synthases (NOS), which are related to muscarinic receptors. 3 In this study, the presence of M2, M3 and M4 subtypes in K562, an erythroleukaemic cell line, was demonstrated by using the reverse transcriptase-polymerase chain reaction. Moreover, the generation of NO induced by carbachol, a non-selective muscarinic agonist, was investigated by using high-performance liquid chromatography to measure changes in extracellular l-citrulline levels. 4 We found that carbachol enhanced l-citrulline production in K562 erythroleukaemic cells. The effect of carbachol on l-citrulline production was antagonized by atropine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), while tropicamide had little effect. These results suggest that the muscarinic receptor M 3 subtype may mediate NO signaling in K562 erythroleukaemic cells. © 2009 Blackwell Publishing Ltd.
  • Publication
    The role of intracellular pathways in the proliferation of human K562 cells mediated by muscarinic receptors
    (PERGAMON-ELSEVIER SCIENCE LTD, 2013) AYDIN OMAY, BANU; Aydin, Banu; Kan, Beki; Cabadak, Hulya
    Muscarinic acetylcholine receptors (mAChRs) are members of the superfamily of G protein coupled receptors (GPCRs). Muscarinic receptors are relatively abundant in the central nervous system and in the peripheral parasympathetic nervous system. Several studies have suggested that muscarinic receptors also mediate some cellular events in hematopoietic cells. K562 erythroleukemia cells contain muscarinic receptors M-2, M-3 and M-4, and activation of muscarinic receptors changes cell proliferation. We examined the effects of several compounds on cell proliferation in K562 erythroleukemia cells. These included a muscarinic receptor agonist carbachol (CCh), a protein kinase inhibitor staurosporine; the phospholipase C inhibitor U73122, the MEK 1-2 inhibitor UO126, the PI3-kinase inhibitor wortmannin, the Ca2+ chelators BAPTA/AM and 2-aminoethoxy-diphenylborate (2APB). In addition, we also investigated muscarinic receptor mediated protein kinase C (PKC) expression in K562 cells. CCh caused a decrease in DNA synthesis in K562 cells supplemented with 1% fetal bovine serum after starvation. Pre-treatment of K562 cells with U73122 and BAPTA/AM antagonized the inhibitory effect of CCh, suggesting that phospholipase C and intracellular calcium are involved in CCh-mediated inhibition of proliferation in K562 cells. Our data also suggest that the regulatory roles of protein kinase C and the MAPK/ERK pathways in K562 cell proliferation are independent of cholinergic activation. (C) 2013 Elsevier Ltd. All rights reserved.