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Öğe Analysis of Relationship Between Dioxin-Like and Estrogenic Bioactivity and Genotoxic Changes in Mammary Epithelial Cells with Nutritional Habits of Breastfeeding Mothers(Wiley, 2017) Agus, Sami; Atasayan, Ozge; Sandal, Suleyman; Mete, Fatih; Eyuboglu, Signem; Yilmaz, Bayram[Abstract Not Available]Öğe Analysis of relationship between dioxin-like and estrogenic bioactivity and genotoxic changes inmammary epithelial cells with nutritional habits of breastfeeding mothers(Rıver st, hoboken 07030-5774, nj usa wıley, 111, 2017) Agus, Sami; Atasayan, Ozge; Sandal, Suleyman; Mete, Fatih; Eyuboglu, Signem; Yilmaz, BayramÖğe Biomonitoring of Genotoxic Changes in Exfoliated Human Mammary Epithelial Cells Collected from Lactating Mothers(Wiley-Blackwell, 2015) Agus, Sami; Atasayan, Ozge; Eyuboglu, Signem; Sandal, Suleyman; Yilmaz, Bayram[Abstract Not Available]Öğe Comparison of Bioactivity of Dioxins in Breast Milk with Body Mass Index in Lactating Mothers(Wiley-Blackwell, 2016) Agus, Sami; Atasayan, Ozge; Sandal, Suleyman; Mete, Fatih; Eyuboglu, Signem; Yilmaz, Bayram[Abstract Not Available]Öğe Correlation of spermiogram profiles with DNA damage in sperm cells of infertile men: a comet assay study(Taylor & Francis Ltd, 2011) Tug, Niyazi; Sandal, Suleyman; Ozelgun, Berna; Yilmaz, BayramWe have investigated a relationship between DNA damage in sperm and spermiogram profiles in the infertile men. Twenty-one non-smoking infertile men <40 years of age with no systemic or genetic disease were randomly selected from the pool of infertile couples applied to our clinic. Sperm samples were collected and evaluated according to WHO guidelines. DNA damage of sperm cells was assessed using neutral comet assay. Fifty cells per slide and two slides per sample were scored to evaluate DNA damage. The cells were visually classified into four categories based on DNA migration such as undamaged (UD), little damage (LD), moderate damage (MD) and significant damage (SD). Total comet scores (TCS) were calculated as: 1 x UD + 2 x LD + 3 x MD + 4 x SD. There was a negative correlation between the percentage of slow-and in situ-motion sperm cells in spermiograms and TCS (p < 0.001 and p < 0.05, respectively). The relationship between the percentage of non-motile sperm cells and TCS was negative (p < 0.001). This study provides new evidence that DNA damage in spermatozoa and sperm motility parameters are negatively correlated. We suggest that evaluation of sperm DNA by the neutral comet assay may be valuable to use in fertility research.Öğe Effects of apelin on reproductive functions: relationship with feeding behavior and energy metabolism(Taylor & Francis Ltd, 2017) Tekin, Suat; Erden, Yavuz; Sandal, Suleyman; Onalan, Ebru Etem; Ozyalin, Fatma; Ozen, Hasan; Yilmaz, BayramApelin is an adipose tissue derived peptidergic hormone. In this study, 40 male Sprague-Dawley rats were used (four groups; n=10). Apelin-13 at three different dosages (1, 5 and 50g/kg) was given intraperitoneally while the control group received vehicle the same route for a period of 14 days. In results, apelin-13 caused significant decreases in serum testosterone, luteinizing hormone and follicle-stimulating hormone levels (p<0.05). Administration of apelin-13 significantly increased body weights, food intake, serum low-density lipoprotein and total cholesterol levels (p<0.05), but caused significant decreases in high-density lipoprotein levels (p<0.05). Serum glucose and triglyceride levels were not significantly altered by apelin-13 administration. Significant decreases in both uncoupling protein (UCP)-1 levels in the white and brown adipose tissues and UCP-3 levels in the biceps muscle (p<0.05) were noted. The findings of the study suggest that apelin-13 may not only lead to obesity by increasing body weight but also cause infertility by suppressing reproductive hormones.Öğe Effects of Peripheral Administration of Kisspeptin on Pubertal Maturation and Serum Leptin Levels in Female Rats(Ortadogu Ad Pres & Publ Co, 2011) Alcin, Ergul; Ozcan, Mete; Ayar, Ahmet; Yilmaz, Bayram; Turkoz, Yusuf; Kelestimur, HalukObjective: The aim of this study was to investigate the effects of exogenous kisspeptin on pubertal maturation in immature female rats. Material and Methods: Wistar female rats were weaned when they were 21 days old. The rats were divided into two groups. Controls (n=10) received saline only (1 ml/kg). Experimental rats (n=9) were intraperitoneally injected with daily 100 nmol kisspeptin-10 between 09.00h-10.00h a.m. starting from the day 26. Body weight and food intake were daily determined, and vaginal opening (VO) was daily monitored starting from day 26. The animals were decapitated when the first diestrus was determined by vaginal smears. Upon decapitation, serum was separated and stored at -20 degrees C until measurement of leptin, luteinizing hormone (LH) and estradiol. Uterus and ovaries were dissected out and weighed. Results: Intraperitoneal injection of 100 nmol kisspeptin-10 did not change median VO ages. There were no differences in food intake, and percentages of body weight change, between control and kisspeptin groups during the experimental period. Kisspeptin administration elicited significant (P<0.01) increases in uterus weight over control values. Serum leptin levels were significantly lower (P<0.05) in kisspeptin-treated group compared to vehicle group. Kisspeptin administration increased (P<0.05) serum LH and estradiol levels. Conclusion: Chronic peripheral administration of kisspeptin-10 does not advance puberty onset as estimated from the date of vaginal opening, but potentiates other conventional indices of maturation of reproductive axis such as elevated uterine weight and increased serum levels of LH and estradiol.Öğe Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention(Springer, 2020) Yilmaz, Bayram; Terekeci, Hakan; Sandal, Suleyman; Kelestimur, FahrettinEndocrine Disrupting Chemicals (EDCs) are a global problem for environmental and human health. They are defined as an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. It is estimated that there are about 1000 chemicals with endocrine-acting properties. EDCs comprise pesticides, fungicides, industrial chemicals, plasticizers, nonylphenols, metals, pharmaceutical agents and phytoestrogens. Human exposure to EDCs mainly occurs by ingestion and to some extent by inhalation and dermal uptake. Most EDCs are lipophilic and bioaccumulate in the adipose tissue, thus they have a very long half-life in the body. It is difficult to assess the full impact of human exposure to EDCs because adverse effects develop latently and manifest at later ages, and in some people do not present. Timing of exposure is of importance. Developing fetus and neonates are the most vulnerable to endocrine disruption. EDCs may interfere with synthesis, action and metabolism of sex steroid hormones that in turn cause developmental and fertility problems, infertility and hormone-sensitive cancers in women and men. Some EDCs exert obesogenic effects that result in disturbance in energy homeostasis. Interference with hypothalamo-pituitary-thyroid and adrenal axes has also been reported. In this review, potential EDCs, their effects and mechanisms of action, epidemiological studies to analyze their effects on human health, bio-detection and chemical identification methods, difficulties in extrapolating experimental findings and studying endocrine disruptors in humans and recommendations for endocrinologists, individuals and policy makers will be discussed in view of the relevant literature.Öğe Evaluation of antioxidant and antiproliferative activities of 1,2-bis (p-amino-phenoxy) ethane derivative Schiff bases and metal complexes(Wiley, 2019) Parlak, Akif Evren; Cakmak, Haluk; Sandal, Suleyman; Yilmaz, Bayram; Sekerci, Memet; Genc, Zuhal Karagoz; Tuzcu, MehmetIn this study, the effects of the two Schiff base derivatives and their metal complexes were tested for MDA concentration, which is an indicator of lipid peroxidation, antioxidant vitamin A, vitamin E, and vitamin C levels in cell culture. A comparison was performed among the groups and it was observed that MDA, vitamin A, vitamin E, and vitamin C concentrations were statistically changed. According to the results, all compounds caused a significant oxidative stress without Zn complexes. Moreover, Mn(II), Cu(II), Zn(II), and Ni(II) complexes of Schiff bases derived from a condensation of 1,2-bis (p-aminophenoxy) ethane with naphthaldehydes and 4-methoxy benzaldehyde were examined in terms of antitumor activity against MCF-7 human breast cancer and L1210 murine leukemia cells. Furthermore, the derivatives were tested for antioxidative and prooxidative effects on MCF-7 breast cancer cells. The compounds which were tested revealed that there was an antitumor activity for MCF-7 and L 1210 cancer cells. Also, some of the compounds induced oxidative harmful.Öğe Genotoxicity profiles in exfoliated human mammary cells recovered from lactating mothers in Istanbul; relationship with demographic and dietary factors(Elsevier, 2012) Yilmaz, Bayram; Sandal, Suleyman; Ayvaci, Habibe; Tug, Niyazi; Vitrinel, AycaWe have investigated the presence of DNA damage in human mammary epithelial cells collected from healthy lactating mothers (age, 20-35 years) who were resident in the Istanbul area. Breast milk (10 ml) was collected from 30 women between one and two weeks post-partum. Demographic information (parity, breast cancer, occupation, duration of residency in Istanbul, consumption of fish, beef and poultry) was also obtained. Milk samples were diluted 1:1 with RPMI 1640 medium and centrifuged to collect cells. The cells were re-suspended and cell viability was determined by use of 0.4% trypan blue. DNA damage was assessed by use of the comet assay (alkaline single-cell gel electrophoresis). Fifty cells per slide and two slides per sample were scored to evaluate DNA damage. The cells were visually classified into four categories on the basis of extent of migration: undamaged (UD), lightly damaged (LD), moderately damaged (MD) and highly damaged (HD). Total comet scores (TCS) were calculated as: 1x UD + 2x LD + 3x MD + 4x HD. Exfoliated mammary cells of the donors showed high (TCS >= 150 a.u.), moderate and low DNA damage in 10 (33.3%), 8 (26.7%) and 12 (40%) mothers, respectively. There was no significant correlation between TCS for DNA damage and the duration of previous breastfeeding, parity or age. None of the mothers was vegetarian, smoker or on any medication. Meat and chicken consumption did not significantly correlate with the TCS values. Fish consumption was significantly correlated with TCS results (Spearman's rho = 0.39, p < 0.05). No significant correlation was found between the DNA-damage scores and the period of residency in Istanbul, but fish consumption increased as the duration of stay was longer (Spearman's rho = 0.53, p < 0.01). These findings suggest that the primary causes of differences in genotoxicity detected in lactating mothers in Istanbul may be of dietary origin. Our experience also confirms that sampling breast milk from lactating mothers provides a valuable and non-invasive tool to study DNA damage in mammary cells. (c) 2012 Elsevier B.V. All rights reserved.Öğe Investigation of epigenetic changes in exfoliated mammary epithelial cells retrieved from lactating women(Wiley-Blackwell, 2015) Atasayan, Ozge; Agus, Sami; Suakar, Oznur; Eyuboglu, Signem; Bayrak, Omer Faruk; Sandal, Suleyman; Yilmaz, Bayram[Abstract Not Available]Öğe Investigation of obesogenic effects of hexachlorobenzene, DDT and DDE in male rats(Academic Press Inc Elsevier Science, 2022) Al-Obaidi, Zeyad Ayad Fadhil; Erdogan, Cihan Sueleyman; Suemer, Engin; Ozguen, Hueseyin Bugra; Gemici, Burcu; Sandal, Sueleyman; Yilmaz, BayramObesity has become a very important public health problem and is increasing globally. Genetics, individual and environmental factors play roles in the etiology of this complex disorder. Recently, several environmental pol-lutants have been suggested to have obesogenic activities. Peroxisome proliferator activating receptor gamma (PPAR gamma), uncoupling protein-1 (UCP1) and their expression in white adipose tissue (WAT) and brown adipose tissue (BAT) play key roles in adipogenesis. UCP3 and irisin were reported to play roles in non-shivering ther-mogenesis. Our primary aim was to investigate obesogenic effects of hexachlorobenzene (HCB), dichlor-odiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) in rats. In addition, thermoregulatory effects of HCB, DDT and DDE were also investigated by analyzing the levels of Ucp3 and irisin. Thirty-two adult male Sprague-Dawley rats were randomly divided into four groups as control, HCB, DDT and DDE. Animals were administered with organochlorine pesticides (OCPs; 5 mg/kg bw) by oral gavage every other day for five weeks. At the end of the experimental period, the animals were sacrificed, BAT and WAT samples were collected to analyze Ppar gamma, Ucp1 and Ucp3 levels. Moreover, skeletal muscle samples were collected to examine Ucp3 and irisin levels. Serum glucose, cholesterol and triglyceride levels were also determined. Body weight and core temperature of the animals were not significantly affected by any of the OCP administration. Serum glucose, cholesterol and triglyceride levels were similar among the experimental groups. Ppar gamma expression was significantly elevated by HCB administration only in WAT (p < 0.05). On the other hand, both Ppar gamma and Ucp1 expressions were diminished in WAT and BAT (p < 0.01) by DDT treatment, while in WAT, DDE signifi-cantly decreased Ppar gamma expression without altering its expression in BAT (p < 0.001). Ucp3 and irisin levels in skeletal muscle were not altered. Our findings show that both DDT and DDE reduce the browning of WAT by suppressing white adipocytes and thus may have obesogenic activity in male rats without altering thermoreg-ulation. In addition, HCB, DDT and DDE-induced alterations in expression of Ppar gamma and Ucp1 in WAT implicates differential regulation of adipogenic processes.Öğe Investigation of Obesogenic Effects of Hexachlorobenzene, Dichlorodiphenyltrichloroethane and Dichlorodiphenyldichloroethylene in a Male Rat Model(Wiley, 2022) Al Obaidi, Zeyad; Erdogan, Cihan Suleyman; Ozgun, Huseyin Bugra; Sumer, Engin; Basol, Burcu Gemici; Sandal, Suleyman; Yilmaz, Bayram[Abstract Not Available]Öğe Kisspeptin-10 elicits triphasic cytosolic calcium responses in immortalized GT1-7 GnRH neurones(Elsevier Ireland Ltd, 2011) Ozcan, Mete; Alcin, Ergul; Ayar, Ahmet; Yilmaz, Bayram; Sandal, Suleyman; Kelestimur, HalukKisspeptins, which are alternatively called as metastin since they were originally identified as products of metastasis suppressor gene KiSS-1, are the natural ligands for the G protein-coupled receptor 54 (GPR54). Kisspeptins are the most potent activators of hypothalamic-pituitary-gonadal (HPG) axis reported to date. The pulsatile pattern of GnRH release, which results in the intermittent release of gonadotropic hormones from the pituitary, has a critical importance for reproductive function but the factors responsible from this release pattern are not known. Therefore, the pattern of kisspeptin-induced intracellular signaling and the role of PKC in the intracellular signaling cascade were investigated by fluorescence calcium imaging using the immortalized GnRH-secreting GT1-7 hypothalamic neurons. Kisspeptin-10 caused a triphasic change characterized by an initial small increase followed by a significant decrease and increase in intracellular free calcium concentrations ([Ca2+](i)). The changes in [Ca2+](i) were significantly attenuated by pre-treatment with protein kinase C inhibitor. The compatibility of appeared mirrored-patterns of kisspeptin-10-induced changes in [Ca2+](i) concentrations in these neurons and GnRH secretion confirm the importance of intracellular calcium flux downstream from GPR54 through PKC signaling pathway. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Öğe Melatonin elicits protein kinase C-mediated calcium response in immortalized GT1-7 GnRH neurons(Elsevier Science Bv, 2012) Kelestimur, Haluk; Ozcan, Mete; Kacar, Emine; Alcin, Ergul; Yilmaz, Bayram; Ayar, AhmetMelatonin is suggested to have effects on hypothalamic-pituitary-gonadal (HPG) axis. The pulsatile pattern of GnRH release, which results in the intermittent release of gonadotropic hormones from the pituitary, has a critical importance for reproductive function but the factors responsible from this release pattern are not known. Calcium is a second messenger involved in hormone release. Therefore, investigation of the effects of melatonin on intracellular free calcium levels ([Ca2+](i)) would provide critical information on hormone release in immortalized GnRH neurons. The pattern of melatonin-induced intracellular calcium signaling was investigated by fluorescence calcium imaging using the immortalized GnRH-secreting GT1-7 hypothalamic neurons. Melatonin caused a significant increase in [Ca2+](i), which was greatly blocked by luzindole, a melatonin antagonist, or attenuated by pre-treatment with protein kinase C inhibitor. This study suggests that melatonin seems to have a direct effect on GnRH neurons. (C) 2011 Elsevier B.V. All rights reserved.Öğe PCB 9 exposure induces endothelial cell death while increasing intracellular calcium and ROS levels(Wiley, 2012) Yilmaz, Bayram; Sandal, Suleyman; Carpenter, David O.Cultured porcine endothelial cells were used to determine the effects of several congeners of polychlorinated biphenyls (PCBs) on cell viability and changes induced by these congeners on levels of intracellular calcium and reactive oxygen species (ROS). Cultured endothelial cells were prepared as a single suspension and run on flow cytometry. Cell viability, intracellular calcium, and ROS concentrations were simultaneously determined by using propidium iodide, Fluo-3, and dihydrorodamine, respectively. The congeners tested included two coplanar tetrachlorinated congeners that have no ortho chlorines, PCBs 77 and 80, a tri-chloro congener which does not have any ortho chlorine, PCB 39, a di-ortho, tetrachlorinated congener, PCB 52, and a mono-ortho congener, PCB 9. PCB 9 was cytotoxic at 5 mu M within 5 min of exposure, and the toxicity increased with time and concentration. None of the other congeners showed consistent cytotoxicity. The cytotoxicity was roughly correlated with elevations in cellular ROS levels, but not with changes in intracellular calcium. To the best of our knowledge, toxicity of lower chlorinated, more volatile congeners such as PCB 9 has not been previously studied. These observations may be taken to explain the elevated risk of cardiovascular disease previously reported among residents living near to hazardous waste sites containing PCBs. (c) 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.Öğe Pinealectomy alters IFN-? and IL-10 levels in primary thymocyte culture of rats(C M B Assoc, 2018) Sahin, Zafer; Sandal, Suleyman; Yilmaz, Bayram; Bulmus, Ozgur; Ozdemir, Gokcen; Kutlu, Selim; Godekmerdan, AhmetMelatonin, produced mainly by the pineal gland, has an immunomodulatory role. However, the effects of the pineal gland and/or melatonin on thymus cytokine levels such as interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-10 are not well known. Twenty-one male Wistar rats (220-250 gr) were randomly divided into three groups (n=7): intact control, sham, and pinealectomy. Primary thymocyte cultures were prepared from each group and dispensed into well plates as Control, DMSO (or vehicle), Sham-pinealectomy, Pinealectomy, Pinealectomy+10 mu M melatonin, and Pinealectomy+100 mu M melatonin. IFN-gamma, IL-4, and IL-10 concentrations were measured in the thymocytes (as nonstimulated and Concanavalin A-stimulated) after 24 h. IFN-gamma levels significantly increased and IL-10 levels significantly decreased in both media prepared from pinealectomized rats. There was no significant difference between the groups in terms of IL-4. In the pinealectomy+100 mu M melatonin group, IFN-gamma and IL-10 levels did not differ from the pinealectomy group. However, the dose of 100 mu M melatonin caused a decrease in levels of IFN-gamma in both thymocyte media and an increase in the concentration of IL-10 in Concanavalin A-stimulated thymocytes. In conclusion, pineal gland and or melatonin affect IFN-gamma and IL-10 levels in the thymus gland.Öğe Pinealectomy alters ıfn-gamma and ıl-10 levels in primary thymocyte culture of rats(C m b assoc, 34 boulevard solferıno, 86000 poıtıers, france, 2018) Sahin, Zafer; Sandal, Suleyman; Yilmaz, Bayram; Bulmus, Ozgur; Ozdemir, Gokcen; Kutlu, Selim; Godekmerdan, Ahmet; Kelestimur, HalukMelatonin, produced mainly by the pineal gland, has an immunomodulatory role. However, the effects of the pineal gland and/or melatonin on thymus cytokine levels such as interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-10 are not well known. Twenty-one male Wistar rats (220-250 gr) were randomly divided into three groups (n=7): intact control, sham, and pinealectomy. Primary thymocyte cultures were prepared from each group and dispensed into well plates as Control, DMSO (or vehicle), Sham-pinealectomy, Pinealectomy, Pinealectomy+10 mu M melatonin, and Pinealectomy+100 mu M melatonin. IFN-gamma, IL-4, and IL-10 concentrations were measured in the thymocytes (as nonstimulated and Concanavalin A-stimulated) after 24 h. IFN-gamma levels significantly increased and IL-10 levels significantly decreased in both media prepared from pinealectomized rats. There was no significant difference between the groups in terms of IL-4. In the pinealectomy+100 mu M melatonin group, IFN-gamma and IL-10 levels did not differ from the pinealectomy group. However, the dose of 100 mu M melatonin caused a decrease in levels of IFN-gamma in both thymocyte media and an increase in the concentration of IL-10 in Concanavalin A-stimulated thymocytes. In conclusion, pineal gland and or melatonin affect IFN-gamma and IL-10 levels in the thymus gland.Öğe Pro-oxidant and antiproliferative effects of the 1,3,4-thiadiazole-based Schiff base and its metal complexes(Taylor & Francis Ltd, 2011) Turan, Nevin; Topcu, M. Fatih; Ergin, Zuhal; Sandal, Suleyman; Tuzcu, Mehmet; Akpolat, Nusret; Yilmaz, BayramAdverse biological activities of Schiff base (SB) derivatives are well known. In this study, the ligand and its metal complexes have been synthesized and characterized by IR, H-1-NMR spectra, elemental analyses, magnetic susceptibility, UV-Vis spectra, and thermogravimetry/differential thermal analysis. From the elemental analyses data, the complexes were proposed to have the general formula [Mn(L)(2) H2O)(2)], [Co(L)(2) H2O)(2)], and [Ni-2(L)(H2O)(4)(Cl)(3)]. From the magnetic moment and UV-Vis spectra data, it was found that the geometrical structures of these complexes are octahedral. In the in vivo experiment, adult male rats were injected subcutaneously with a new SB (L) and its [Mn(L)(2)(H2O)(2)], [Co(L)(2)(H2O)(2)], and [Ni-2(L)(H2O)(4)(Cl)(3)] complexes (25 mg/kg body weight) and were then sacrificed 16 days later. Effects of these compounds on serum antioxidant vitamins (i.e., vitamins A, E, and C) and malondialdehyde (MDA) levels were measured in blood serum, liver, and kidney tissues. In an in vitro experiment, antiproliferative effects of these compounds were assessed on the human breast carcinoma MCF-7 and murine leukemia L1210 cell lines. Serum MDA and vitamins A, E, and C levels did not change by the treatments. However, in the kidney and liver tissues, MDA levels were higher, whereas vitamin levels were lower in treatment groups, compared to the control group. All compounds inhibited cell proliferation of MCF-7 and L1210 cancer cell lines in a dose- and time-dependent manner. In conclusion, SB derivatives tested in the current study induced oxidative stress in vivo and exhibited antiproliferative effects in an in vitro culture system.
