pinar erkekoglu - Academia.edu (original) (raw)

Papers by pinar erkekoglu

Turkiye Klinikleri Journal of Pharmacy Sciences, 2017

Alkylanilines are ubiquitous environmental chemicals. Most individuals are subject to lifelong ex... more Alkylanilines are ubiquitous environmental chemicals. Most individuals are subject to lifelong exposure to these compounds and this exposure can cause toxic effects in human bladder. It was shown that other than main compounds, their oxidative metabolites (oor p-phenol derivatives) are cytotoxic. Phenolic metabolite of 3,5-dimethylaniline is 3,5-dimethylaminophenol (3,5-DMAP). It is oxidized to a quinoneimine further metabolite by Phase I enzymes. The aim of this study is to determine whether varying concentrations (2.5, 5, 10, 25, 50, 100 μg/ml) of 3,5-DMAP causes mutagenic effects in bacteria and mammalian cells. To investigate the mutagenicity of 3,5-DMAP in bacteria, “Ames test” was applied. Salmonella typhimurium, TA98 and TA100 strains, were used to determine base-pair and frame shift mutations, respectively (with/ without S9 fraction). To determine the mutagenicity of 3,5-DMAP in mammalian cells, “hypoxanthine phosphoribosyltransferase 1 (HPRT) test” was performed on CHO cell...

Journal of Environmental Pathology, Toxicology and Oncology, 2016

Epithelial-mesenchymal transition (EMT) is a process during which epithelial cells lose their pol... more Epithelial-mesenchymal transition (EMT) is a process during which epithelial cells lose their polarity and ability to adhere. Instead, they gain properties to move, migrate through the extracellular matrix, become invasive, and finally become mesenchymal stem cells. This trans-differentiation is critical for embryo development, wound healing, and stem cell behavior. However, this same phenomenon is also observed in cancer progression. Phthalates and bisphenol A (BPA) are endocrine-disrupting chemicals (EDCs) that are linked to complex human diseases. These chemicals are suggested to disrupt normal hormonal balance (usually by existing estrogenic/antiandrogenic properties) and stimulate the development of reproductive tumors and steroid hormone-dependent cancers, such as breast cancer. Di(2-ethylhexyl) phthalate (DEHP), the most abundant phthalate, was shown to induce DNA damage in human cells via multiple molecular signals that include altered apoptosis and mitotic rate, increased cell proliferation, tumor mobility, and invasiveness of tumor cells. DEHP was also shown to inhibit gap junction intercellular communication and tight junctions and promote EMT. Phthalates may also cause the proliferation and metastasis of cancer cells and tumor progression via up-regulating histone deacetylase 6 (HDAC6). Phthalates can activate peroxisome proliferator activated receptors (PPARs) that may eventually lead to high proliferation of cancer cells. However, in ovarian cells the expression of Snail, Slug, and vimentin was enhanced by the treatment of BPA, whereas E-cadherin was decreased. Mechanistic studies are needed to show the underlying mechanisms of EMT caused by different EDCs.

Pediatrics International, 2015

Selenium is a trace element required for the functioning of immune system. Neonatal sepsis is a s... more Selenium is a trace element required for the functioning of immune system. Neonatal sepsis is a serious condition leading to morbidity and mortality among neonates worldwide. The purpose of this study was to determine the selenium and plasma selenoprotein P (SePP) levels, selenoenzyme activities, and alterations in oxidant/antioxidant status with immune biomarkers in neonates with clinical (n = 27) and proven neonatal sepsis (n = 25). Erythrocyte selenium levels with plasma selenoprotein P (SePP) levels; plasma lipid peroxidation (LP), protein oxidation and total antioxidant capacity and erythrocyte total glutathione (GSH) concentrations; erythrocyte glutathione peroxidase (GPx), thioredoxin reductase (TrxR), catalase (CAT) and total superoxide dismutase (SOD) activities were measured spectrophotometrically/spectrofluorometrically. Besides, plasma interleukin 2 and 6 levels were determined. Erythrocyte selenium and SePP levels were markedly lower both in clinical and proven sepsis vs. Erythrocyte GPx activity was higher only in clinical sepsis group. TrxR activity was markedly lower in proven sepsis. SOD activity and GSH levels were markedly higher both in clinical sepsis and proven sepsis. CAT activity was significantly higher both in clinical sepsis and proven sepsis. LP and protein oxidation levels were significantly higher in both of the groups. Our findings showed that both Se-dependent and Se-independent blood redox systems were altered in sepsis and we can suggest that sepsis causes an imbalance between cellular antioxidant and oxidant state.

Toxicology Letters, 2010

Abstracts / Toxicology Letters 196S (2010) S37-S351 S163 4 weeks, weighted 30-45 g were used (n =... more Abstracts / Toxicology Letters 196S (2010) S37-S351 S163 4 weeks, weighted 30-45 g were used (n = 10). Tail venous blood of mice were taken at 1, 7 and 14th days of the experiment. For the half dose, statistical significance have been found when the results of 1st and 14th days of the experiment compared (p < 0.01). Similar significances have been observed when the results of 1st and 7th days of the experiment compared (p < 0.01). In the double doses, statistical significance have been found when the results of 1st and 7th (p < 0.01) and 1st and 14th (p < 0.05) days of the experiment compared as well. Obtained results also compared with the results of the control group. We have not found any differences between the dose groups and control group in the consideration of 1st day of the experimental results (p > 0.05). On the other hand significant differences have been observed when ×2 dose-treated group is compared with control group by 7th day (p < 0.01).

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2015

Di(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer for synthetic polymers, is known to h... more Di(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer for synthetic polymers, is known to have endocrine disruptive potential, reproductive toxicity, and induces hepatic carcinogenesis in rodents. Selenium (Se) is a component of several selenoenzymes which are essential for cellular antioxidant defense and for the functions of mammalian reproductive system. The present study was designed to investigate the effects of DEHP exposure on trace element distribution in liver, testis, and kidney tissues and plasma of Se-deficient and Se-supplemented rats. Se deficiency was produced by feeding 3-week old Sprague-Dawley rats with ≤0.05mg Se/kg diet for 5 weeks, and supplementation group were on 1mg Se/kg diet. DEHP treated groups received 1000mg/kg dose by gavage during the last 10 days of feeding period. Se, zinc (Zn), copper (Cu), iron (Fe) and manganese (Mn) levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). Se supplementation caused significant increases...

Biological Trace Element Research, 2009

Considering the potential adverse effects of selenium and iodine deficiencies, and taking into ac... more Considering the potential adverse effects of selenium and iodine deficiencies, and taking into account the widespread but often careless use of pyrethroid insecticides and their possible endocrine-disrupting effects, this study was undertaken to investigate the effects of fenvalerate on thyroid hormone parameters in both healthy and selenium-and/or iodine-deficient rats. Fenvalerate exposure had no effect on the TT4 levels of healthy controls but caused significant increases both in iodine deficiency (ID) and selenium plus iodine deficiency (ISeD), and a significant decrease in selenium deficiency (SeD). Dramatic increases in TT3 of all groups were observed by fenvalerate. Moreover, it caused insignificant decrease of thyroid stimulating hormone in healthy controls, no effect in SeD, and significant elevation in ID and ISeD. These results, thus, showed that the widely used pyrethroid insecticide fenvalerate has the potential to change significantly thyroid hormone parameters both in normal and deficiency states, and consequences of its thyroid status modifying effect might be of critical importance particularly in sensitive individuals and patients with thyroid dysfunction.

Journal of Environmental Pathology, Toxicology and Oncology, 2012

This study was designed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on thyro... more This study was designed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on thyroid hormone levels and oxidant/antioxidant parameters in the rat and to evaluate the effects of selenium status. Selenium deficiency was produced by feeding 3-week-old Sprague-Dawley rats with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 mg selenium/kg body weight for 5 weeks, and the supplementation group received a diet of 1 mg selenium/kg body weight. DEHP-treated groups received the compound at a dose of 1000 mg/kg by gavage during the last 10 days of the feeding period. Levels of thyroid hormone levels as well as selenoenzyme (glutathione peroxidase 1, thioredoxin reductase), catalase, and superoxide dismutase (SOD) activity and thiobarbituric acid reactive substance (TBARS) were measured. Total thyroxine (TT4) levels decreased significantly with DEHP exposure (~25%), whereas TT3 level was not altered. The TT4 lowering effect of DEHP exposure was not affected by selenium deficiency but was observed when animals exposed to DEHP received a selenium supplement. DEHP was found to alter the antioxidant status and induce oxidative stress in rat thyroid by increasing SOD activity (~30%) and TBARS levels (~35%). The effects of DEHP were much more pronounced in selenium-deficient rats, as evidenced by significant increases in SOD activity (~65%) and TBARS levels (~55%) compared with the control levels. Thus, these results show the thyroid-disrupting effect of DEHP in rats and protection by selenium.

Toxicology Mechanisms and Methods, 2014

Many of the environmental, occupational and industrial chemicals are able to generate reactive ox... more Many of the environmental, occupational and industrial chemicals are able to generate reactive oxygen species (ROS) and cause oxidative stress. ROS may lead to genotoxicity, which is suggested to contribute to the pathophysiology of many human diseases, including inflammatory diseases and cancer. Phthalates are ubiquitous environmental chemicals and are well-known peroxisome proliferators (PPs) and endocrine disruptors. Several in vivo and in vitro studies have been conducted concerning the carcinogenic and mutagenic effects of phthalates. Di(2-ethylhexyl)-phthalate (DEHP) and several other phthalates are shown to be hepatocarcinogenic in rodents. The underlying factor in the hepatocarcinogenesis is suggested to be their ability to generate ROS and cause genotoxicity. Several methods, including chromosomal aberration test, Ames test, micronucleus assay and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation test and Comet assay, have been used to determine genotoxic properties of phthalates. Comet assay has been an important tool in the measurement of the genotoxic potential of many chemicals, including phthalates. In this review, we will mainly focus on the studies, which were conducted on the DNA damage caused by different phthalate esters and protection studies against the genotoxicity of these chemicals.

Toxicon, 2010

This study has been undertaken to investigate the regional and seasonal variability in ochratoxin... more This study has been undertaken to investigate the regional and seasonal variability in ochratoxin A (OTA) exposure of healthy population living in Black Sea and Mediterranean regions of Turkey by measuring serum OTA concentrations. The mean serum concentrations of OTA were determined to be 0.137 ng/mL (0.0306-0.887 ng/mL) and 0.312 ng/mL (0.028-1.496 ng/mL) in all samples for winter and summer, respectively by enzyme-linked immunosorbent assay (ELISA). The differences between mean values of OTA in all serum samples collected in summer and winter were statistically significant. The highest OTA concentration was determined in the children living in Black Sea Region in summer. The mean daily intake levels of OTA in all samples were estimated as 0.182 ng/kg b.w./day and 0.408 ng/kg b.w./day in winter and summer, respectively. The results showed that the mean serum concentrations of OTA in healthy population in both regions were found not to be exceeded 1 ng/mL in agreement with the distribution reported in most European countries and that the daily intake levels of OTA were calculated below the tolerable daily intake levels given by regulatory authorities. However, overall results suggest that Turkish population living in these regions is continuously exposed to OTA and that the exposure levels are also elevated in summer period compared to winter.

Toxicon, 2013

Ochratoxin A (OTA), one of the most prevalent mycotoxins in the world, has nephrotoxic and hepato... more Ochratoxin A (OTA), one of the most prevalent mycotoxins in the world, has nephrotoxic and hepatotoxic properties. Lycopene is an important carotenoid and has a high singlet-oxygen and free-radical scavenging capacity. This study was designed to investigate the possible protective effects of lycopene against the genotoxicity of OTA in rat tissues using the alkaline comet assay. Male Sprague-Dawley rats were used in the experiments. OTA (0.5 mg/kg b.w./day) was administered by gavage for 14 days, whereas lycopene was applied on the last 7 days or for 14 days of the feeding period, with OTA treatment. OTA caused marked increases in tail length, tail moment, and tail intensity vs. control both in the kidney and liver cells, but not in the lymphocytes. Lycopene administration alone for 7 and 14 days did not provide any significant change in DNA damage of the lymphocytes, renal and hepatic cells vs. controls. However, lycopene for both 7 and 14 days, with OTA exposure in renal and hepatic cells, supplied significant decreases in tail length, tail moment, and tail intensity vs. OTA-exposed rats. The effect of 14 days supplementation seemed to be more protective, particularly against hepatic cells. These results suggest that lycopene may protect hepatic and renal tissue from OTA-induced DNA damage.

Toxicology Mechanisms and Methods, 2010

Toxicology Letters, 2012

Abstracts / Toxicology Letters 211S (2012) S43-S216 cardiomyopathy hamsters (Bio14.6) at 6 weeks ... more Abstracts / Toxicology Letters 211S (2012) S43-S216 cardiomyopathy hamsters (Bio14.6) at 6 weeks of age (n = 6, each group). Results and conclusion: At 6 weeks of age, there are no significant differences in the heart weight and left ventricular function monitored by echocardiography among three strains. However, plasma cardiac troponin T concentration is significantly increased in TO-2 compared with control hamsters at 6 weeks of age. 2D Oxyblot analysis detected 18 proteins with increased carbonyl level in cardiomyopathy hamster compared with control hamster. We found that the carbonyl modification of succinyl-CoA:3-ketoacidcoenzyme A transferase 1 was markedly increased in both TO-2 and Bio 14.6. In addition, the carbonylated levels of citrate synthase and dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex were significantly increased in both two cardiomyopathy hamsters. Oxidative damage to the proteins related ATP synthesis, including citric acid cycle and electron transport system, in the heart may lead to the left ventricular dysfunction, which contributes to pathogenesis of cardiomyopathy.

Toxicology Letters, 2006

metal contaminations should seriously be taken into concern. It is essential to take special care... more metal contaminations should seriously be taken into concern. It is essential to take special care throughout the entire process of manufacturing foods for infants and young children, as the fragility of them requires an increased safety. We suggest that contaminations with metals, especially aluminum should be routinely monitored in foods for babies in order to reduce food-borne hazards in infants and young children. In 2000, EU approval was given for the addition of phytosterols to yellow fat spreads based on a comprehensive toxicology dataset. Results from a post-launch monitoring (PLM) programme showed that phytosterol intakes were lower than originally predicted. Based on these findings a second Novel Foods application was made to extend the approval to include other product types such as milk and yoghurt. A novel approach was required to produce a risk assessment demonstrating that these additional sources of phytosterols in the diet would not lead to safe levels being exceeded. Food consumption data for the three different product types (spreads, milk and yoghurt) were obtained from National dietary surveys where these were available in countries such as the UK and the Netherlands. Individual dietary records were then used to model the intake of phytosterols from the three different products. It was assumed that all milk, yogurt and spread consumed was replaced with phytosterolcontaining products, taking into account not only the total amount of the product type consumed but also which of the products types are eaten in combination For the majority of EU countries detailed dietary survey data were not publicly available. However, it was possible to obtain consumer purchase data for these product types for some countries which could also used to calculate the intake of the different food products. As before, a worst case scenario was used to estimate phytosterol intake by assuming that all milk, yogurt and spread consumed was replaced with phytosterol-containing products. The accuracy of this data was assessed by comparing the individual intakes estimated from the National dietary surveys in UK and Netherlands with values estimated from the consumer purchase data collected in these countries. Overall, the intake modelling demonstrated that phytosterols could be added to different product types without intakes exceeding safe levels identified in toxicology studies. Novel Foods approval was granted for the use of phytosterols in milk and yoghurt type products. A sensitive and specific in house method using onestep clean up procedure based on gel permeation chromatography was developed. The method is suitable for determination of benzo(a)pyrene in edible oil. The main improvements compared with previous conventionale procedures are that analyte peak does not overlap with matrix peaks and that the one-step procedure of purification is rapid and simple with clearly improved analytical performance. The quantitative analysis was performed by highperformance liquid chromatograph with fluorescence detector and confirmation was based on the GC-MS. The mean recovery rate of benzo(a)pyrene studied at three concentration levels (n = 9) was 101% (R.S.D. 2.06%). No matrix effect was detected for different oils (olive, sunflower and rape oil). The limit of detection of benzo(a)pyrene by fluorescence was 0.1 g/kg (R.S.D. 5.54%) and the limit of quantification was 0.2 g/kg (R.S.D. 2.19%).