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    7-Ethoxyresorufin O-deethylase and glutathione S-transferase activities of rats treated with morin, 7,12-dimethylbenz[a] anthracene and endosulfan
    (Wiley-Blackwell, 2016) Sapmaz, Canan; Fırat, Tülin; Kükner, Aysel; Bozcaarmutlu, Azra
    [No Abstract Available]
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    Aldrin epoxidation in flathead Mullet (Mugil cephalus) : possible involvement of CYP1A and CYP3A
    (Wiley, 2014) Bozcaarmutlu, Azra; Turna, Sema; Sapmaz, Canan; Arınç, Emel; Karakaş, Serpil Yenisoy
    The primary objective of this study was to determine specific cytochrome P450 isozyme(s) involved in the metabolism of aldrin to its toxic metabolite dieldrin in flathead mullet (Mugil cephalus) liver microsomes. To identify the cytochrome P450 isozyme responsible for the aldrin metabolism in mullet liver, the effects of mammalian-specific cytochrome P450 inhibitors and substrates were determined in the epoxidation reaction of aldrin. CYP3A-related inhibitors, ketoconazole, SKF-525A, and cimetidine, inhibited the metabolism of aldrin. The contribution of CYP1A to the aldrin metabolism was shown by the inhibition of 7-ethoxyresorufin-O-deethylase activity in the presence of aldrin. The results indicate that CY1A and CYP3A are the cytochrome P450s involved in aldrin epoxidase activity in mullet. In addition, the suitability of aldrin epoxidase activity for monitoring of environmental pollution was also assessed in the fish samples caught from four different locations of the West Black Sea coast of Turkey.
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    Alkoxyresorufin O-dealkylase activities in rats treated with 7,12-dimethylbenz[a]anthracene and endosulfan
    (Wiley-Blackwell, 2015) Sapmaz, Canan; Fırat, Tülin; Kükner, Aysel; Bozcaarmutlu, Azra
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    Alteration in xenobiotic metabolizing enzyme activities with morin and 7,12-dimethylbenz(a) anthracene in diabetic male rats
    (Wiley-Blackwell, 2015) Sapmaz, Canan; Fırat, Tülin; Kükner, Aysel; Bozcaarmutlu, Azra
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    Assessment of pollution in the west black sea coast of Turkey using biomarker responses in fish
    (Elsevier Sci Ltd, 2009) Bozcaarmutlu, Azra; Sapmaz, Canan; Aygün, Züleyha; Arınç, Emel
    Aim of this study was to determine the extent of pollution in the West Black Sea Coast of Turkey by measuring CYP1A associated EROD activity, phase II enzyme, glutathione S-transferase and antioxidant enzymes, catalase and glutathione reductase activities and immunochemical detection of CYP1A protein level in the liver of mullet. The fish samples were caught from six locations having a varying degree of pollution in the West Black Sea Region of Turkey in August 2005, 2006 and 2007. Mullets caught from Zonguldak Harbour, Eregli Harbour and Guluc Stream's Mouth displayed 6-9-fold higher EROD, 2-4-fold higher glutathione S-transferase and 2-3-fold higher catalase activities than the reference site, Amasra. Total polyaromatic hydrocarbon levels in mullets caught from these locations were also significantly higher (2-4-fold) than Amasra. The results Of this Study indicate that Zonguldak Harbour, Eregli Harbour and Guluc Stream are highly Polluted by polycyclic aromatic hydrocarbons and related contaminants. (C) 2009 Elsevier Ltd. All rights reserved.
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    Biomarker responses in So-luy mullet (Mugil soiuy) to toxic organic pollutants in the west Black sea region of Turkey
    (Elsevier Sci Ltd, 2008) Bozcaarmutlu, Azra; Sapmaz, Canan; Aygün, Züleyha; Arınç, Emel
    The Black Sea has been increasingly threatened by pollutants over the past decades due to uncontrolled shipping, accidental crude oil spills, and discharge of industrial and domestic wastes from coastal settlements. There are few studies concerning biomarker responses to pollutants in the Black Sea. In this study, CYP1A-associated 7-ethoxyresorufin O-deethylase (EROD) activity (induced by polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dioxins) the phase II detoxifying enzyme glutathione S-transferase (GST) and the antioxidant defense enzyme catalase (CAT) were used as biomarkers. Fish were collected in August 2005 by net, from five sites representing a pollution gradient in the West Black Sea Region of Turkey. Mullet collected from the Zonguldak Harbor, a highly urbanized and industrial city in the West Black Sea Region, had 7-fold higher EROD activities than Kefken, a less contaminated site. The mullet samples collected from Sakarya River Mouth, Melen Stream Mouth and Guluc Stream Mouth displayed between 2 and 3 fold higher EROD activities compared to Kefken. GST activities of the samples from the four sites with elevated EROD activities ranged between 2- and 3-fold higher than in fish from Kefken. Likewise CAT activities of samples from these four sites were 4-fold higher than Kefken. In this study, the elevated biomarker responses indicate that Zonguldak Harbour, Sakarya River, Melen and Guluc Stream have tendency to create a local pollution in the Black Sea. Additionally, the pollution status of Zonguldak Harbour was the highest between the sampling sites with regard to toxic organic pollutants. (Supported by TUBITAK (Project No. 104Y083). © 2008 Published by Elsevier Ltd.
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    Biomonitoring of the toxic pollutants by using mullet liver enzymes in the West Black Sea region of Turkey
    (Blackwell Publishing, 2006) Bozcaarmutlu, Azra; Aygün, Züleyha; Sapmaz, Canan; Arınç, Emel
    In this study, CYP 1A associated 7-ethoxyresorufin O-deethylase (EROD) activities (indicative of exposure to toxic carcinogenic persistent organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls (PCBs)) were measured in liver microsomes of mullet (Mugil soiuy) in the West Black Sea Region of Turkey.
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    Characterization of aldrin epoxidation in flathead mullet (Mugil cephalus) liver microsomes: Involvement of CYP3A
    (Elsevier Ireland Ltd, 2011) Bozcaarmutlu, Azra; Turna, Sema; Erden, Canan Sapmaz; Yenisoy-Karakaş, Serpil; Arınç, E.
    Toxic organochlorine pesticides, aldrin and its metabolite dieldrin, have been reported to contaminate the aquatic environment highly. In the present study, epoxidation reaction of aldrin to dieldrin was studied in mullet liver microsomes and contribution of cytochrome P450 isozyme(s) was determined by using specific cytochrome P450 inhibitors and substrate. Flathead mullet samples (Mugil cephalus) were caught from the West Black Sea Region of Turkey. Fish liver microsomes were prepared by differential centrifugation. Epoxidation of aldrin to dieldrin was determined by measuring the amount of dieldrin produced using gas chromatography and electron capture detector. Aldrin epoxidation was linear with time up to 60 min and with protein concentration up to 10 mg/mL. Maximal fish liver aldrin epoxidase activity was observed at pH 7.6. Aldrin epoxidase exhibited monophasic kinetics with apparent Km value of 140 μM for aldrin. The enzyme activity was inhibited approximately by 9% and 16% by methanol and DMSO, respectively. On the other hand, aldrin epoxidation was enhanced by about 113% with 2% ethanol in the incubation medium. Ketoconazole (CYP3A inhibitor), potentially inhibited the metabolism of aldrin, tolbutamide (CYP2C substrate), and alpha-naphthoflavone (CYP1A inhibitor) did not show inhibition. The results of this study strongly suggest that CYP3A is the cytochrome P450 isozyme involved in aldrin epoxidation in mullet liver microsomes whereas CYP2C and CYP1A are not involved.
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    Combined use of PAH levels and EROD activities in the determination of PAH pollution in flathead mullet (Mugil cephalus) caught from the West Black Sea coast of Turkey
    (Springer Heidelberg, 2015) Bozcaarmutlu, Azra; Sapmaz, Canan; Kaleli, Gizem; Turna, Sema; Karakaş, Serpil Yenisoy
    The aim of this study was to determine the extent of polycyclic aromatic hydrocarbon (PAH) pollution by measuring PAH levels and 7-ethoxyresorufin-O-deethylase (EROD) activities in flathead mullet (Mugil cephalus) samples caught from the West Black Sea coast of Turkey. The fish samples were caught in August 2008-2011. The levels of 13 PAHs were measured by high-performance liquid chromatography (HPLC) in the liver of fish. Most of the measured PAHs had three rings (low molecular weight). The frequencies of detection of PAHs were higher in fish samples caught from Zonguldak Harbour and Guluc Stream Mouth than those from Sakarya River Mouth, Amasra and Kefken. EROD activities and cytochrome P4501A (CYP1A) protein level were also measured in the fish liver microsomes. Highly elevated EROD activities and CYP1A levels were measured in the mullet samples caught from Zonguldak Harbour and Guluc Stream than those from Amasra and Kefken. The detection of PAHs in the liver of fish samples shows recent exposure to PAHs. The chemical analyses of PAHs and EROD activity results together reflected the extent of PAH pollution in the livers of fish caught from the West Black Sea coast of Turkey. The results indicate that Zonguldak Harbour is the most polluted site in the West Black Sea coast of Turkey.
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    Competitive Inhibition of CYP1A1 by flavonoids, quercetin and rutin: Promising agents for cancer prevention
    (Taylor & Francis Inc, 2010) YIlmaz, Duygu; Bozcaarmutlu, Azra; Arınç, Emel
    [No Abstract Available]
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    Decreasing myocardial estrogen receptors and antioxidant activity may be responsible for increasing ischemia- and reperfusion-induced ventricular arrhythmia in older female rats
    (Elsevier Inc., 2021) Bozdoğan, Ömer; Bozcaarmutlu, Azra; Kaya, Salih Tunç; Sapmaz, Canan; Özarslan, Talat Oğulcan; Ekşioğlu, Didem; Yaşar, Selçuk
    Aims: This study aimed to investigate the relationship between ischemia- and reperfusion-induced arrhythmia and blood serum estrogen levels, myocardial estrogen receptor levels, antioxidant enzyme activities, and the effects of the estrogen receptor blocker, fulvestrant (ICI 182 780). Main methods: A total of 102 female Sprague-Dawley rats of different ages (2–3, 6–7, 14–15, and 20–21 months) were used in this study. Myocardial ischemia was produced by ligation of the descending branch of the left anterior descending coronary artery, and reperfusion was produced by releasing this artery. An electrocardiogram (ECG) and blood pressure were recorded for 6 min of ischemia and 6 min of reperfusion. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), estrogen receptor ? (ER?), and estrogen receptor ? (ER?) in myocardial tissue and 17 beta-estradiol (E2) in blood serum were measured via enzyme-linked immunosorbent assay (ELISA). The results were compared using a Mann–Whitney U test, one-way analysis of variance (ANOVA), and a student's t-test. Key findings: It is not the changes in serum estrogen levels but the decreasing myocardial estrogen receptors and antioxidant activities that could be responsible for the occurrence of more severe arrhythmia in response to reperfusion in older female rats. Significance: The death rate due to a heart attack in younger men is higher than in women. However, it equalizes after the menopausal stage in women. In this study, the reason for the increasing sudden post-menopausal death rate in women was investigated experimentally.
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    Determination of organochlorine pesticide concentrations in flathead mullet (Mugil cephalus) caught from the western Black Sea coast of Turkey
    (Springer, 2014) Bozcaarmutlu, Azra; Turna, Sema; Sapmaz, Canan; Karakaş, Serpil Yenisoy
    The objective of this study was to determine the levels of 14 organochlorine pesticides (OCPs) in flathead mullet (Mugil cephalus) caught from the western Black Sea coast of Turkey. The fish samples were caught from five different locations of the western Black Sea coast of Turkey in August 2009. Organochlorine pesticides were extracted from the liver tissues, and then the levels of OCPs were measured using gas chromatography with an electron capture detector. Organochlorine pesticides were detected in all locations. The levels of total OCPs in fish samples ranged between 0.224 and 1.103 mu g g(-1) dry weight in the western Black Sea coast of Turkey. DDT, beta-HCH, and endosulfan I were the dominant OCPs in the fish samples. The levels of DDT in fish samples ranged between 0.081 and 0.186 mu g g(-1) dry weight. The levels of total HCH in fish samples ranged between 0.007 and 0.376 mu g g(-1) dry weight in the western Black Sea coast of Turkey. Although the usage of OCPs was banned in Turkey, the results of this study clearly indicated the presence of OCPs in the western Black Sea coast of Turkey and exposure of living organisms to these chemicals.
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    The effect of co-administration of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rat liver
    (Taylor & Francis Ltd, 2020) Bozcaarmutlu, Azra; Sapmaz, Canan; Bozdoğan, Ömer; Kükner, Aysel; Kılınç, Leyla; Kaya, Salih Tunç; Özarslan, Oğulcan Talat; Ekşioğlu, Didem
    It is possible to use plant-derived antioxidant molecules in the form of dietary supplements. However, dietary supplement-drug interaction pattern has not been well defined for most of these products. The aim of this study was to determine the effects of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rats. Streptozotocin was administered to create experimental diabetes. Resveratrol (5 mg/kg) (R), glibenclamide (5 mg/kg) (G), and berberine (10 mg/kg) (B) were administered individually or in combinations in DMSO by intraperitoneal administration route to the diabetic rats. DMSO was also given to non-diabetic control (C) and diabetic control (D) groups. Livers of rats were taken under anesthesia at the end of the treatment period (12 days). Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), aniline 4-hydroxylase (A4H), erythromycin N-demethylase (ERND), glutathione S-transferase (GST), catalase (CAT), and glutathione reductase (GR) activities were measured in microsomes and cytosols. In addition, histomorphological studies were also performed in the liver tissues. EROD activity of D+R was significantly higher than C and D+R+B. PROD activity of D+R was significantly higher than C, D, D+R+G, D+R+B, and D+R+B+ G. PROD activity of D+B was significantly higher than C and D+R+B. ERND activity of D+R was significantly higher than D+R+G and D+R+B. GST activity of D+R was significantly higher than D+R+G. CAT activity of D+B was significantly lower than C. It is clear that co-administration of resveratrol, berberine, and glibenclamide modifies some of the important xenobiotic metabolizing enzyme activities. Resveratrol and berberine have the potential to cause dietary supplement-drug interaction.
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    Effect of co-administration of endosulfan and morin on biomarker enzyme activies in rat liver
    (Wiley-Blackwell, 2014) Sapmaz, Canan; Fırat, Tülin; Kükner, Aysel; Bozcaarmutlu, Azra
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    Effect of mercury, cadmium, nickel, chromium and zinc on kinetic properties of NADPH-cytochrome P450 reductase purified from leaping mullet (Liza saliens)
    (Pergamon-Elsevier Science Ltd, 2007) Bozcaarmutlu, Azra; Arınç, Emel
    Information on the mechanism of metal ion inhibition of NADPH-cytochrome P450 reductase is limited. The purpose of the present paper was to elucidate in vitro effect of Hg(+2), Cd(+2), Ni(+2), Cr(+3) and Zn(+2) ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase was purified from detergent-solubilized liver microsomes from leaping mullet (Liza saliens). All of the metal ions caused inhibition of the enzyme activity except Zn(+2). At 50 mu M metal concentration, Hg(+2) inhibited the cytochrome P450 reductase activity completely (100%), while, at the same concentrations, Cd(+2), Cr(+3) and Ni(+2) caused 66%, 65% and 37% inhibition, respectively. At 50 mu M metal concentration, Zn(+2) had no apparent effect on cytochrome P450 reductase activity. The IC(50) values of HgCl(2), CrCl(3), CdCl(2) and NiCl(2) were estimated to be 0.07 mu M, 24 mu M, 33 mu M and 143 mu M, respectively. Of the metal ions tested, Hg(+2) exhibited much higher inhibitory effect at lower concentrations, so it was evidently a more potent inhibitor than the others. All four metal ions displayed noncompetitive type of inhibition mechanism for the purified reductase as analyzed by Dixon plot. K(i) values of Hg(+2), Cr(+3), Cd(+2) and Ni(+2) were calculated from Dixon plots as 0.048 mu M, 18 mu M, 73 mu M and 329 mu M, respectively. (c) 2006 Elsevier Ltd. All rights reserved.
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    Effect of morin on cytochrome P450-dependent monooxygenase activities in 7,12-dimethylbenz[a]anthracene treated rats
    (Wiley-Blackwell, 2014) Sapmaz, Canan; Fırat, Tülin; Kükner, Aysel; Bozcaarmutlu, Azra
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    Effect of total isoflavones found in soybean on vitellogenin production in common carp
    (2009) Türker, Hakan; Bozcaarmutlu, Azra
    Balık diyetlerinde temel protein kaynağı olan balık ununun yerine soya fasulyesi yemi yaygın olarak kullanılmaktadır. Fakat soya fasulyesinin fitoestrojenik özellikleri balıklarda üremeyi etkileyeceğinden, diyetlerde soya fasulyesi bazlı yemlerin kullanılması endişe oluşturmaktadır. Bu çalışmanın amacı çeşitli konsantrasyonlarda hazırlanan toplam isoflavon içeren soya fasülyesi özütleri ile sazangil balıklarında vitellojenin proteini üretimi arasında bir ilişkinin olup olmadığını belirlemektir. Beş farklı dozda (içerdikleri toplam isofavon oranlarına göre 0, 250, 500, 1.000 ve 10.000 mg/kg) hazırlanan ticari soya fasulyesi özütleri fitoestrojen konsantrasyonlarının vitellojenin sentezine etkisini belirlemek için dişi ve erkek sazanda, Cyprinius carpio L., test edilmiştir. Bütün balık grupları içinde özütlerin büyümeye etkisinde herhangi bir farklılık bulunamamıştır. Soya özütlerinin bütün konsantrasyonları erkeklerde GSI değerini düşürmüş, fakat dişilerin GSI değerinde 500 mg/kg soya özütü konsantasyonuna kadar arttırmış daha sonra da yüksek dozlarda da düşürmüştür. Bu da plazma içindeki vitellojenin seviyesinin inhibisyonu ve indüklenmesi ile ilişkilendirilmiştir. GSI ve vitellojenin değerindeki değişikliklerin, fitoestrojenlere maruz kalan bireyleri belirleyebilecek hassas bir belirteç olduğunu ortaya çıkarmıştır. Daha yüksek dozlardaki isoflavonlar her iki cinsiyetteki balıklar için daha fazla vitellojenin üretmiştir. Bu çalışma sonucunda fitoestrojen içeren soya fasulyesi özütleriyle hazırlanan yemlerle beslenen her iki cinsiyetteki balıkların vitellojenin üretiminin indüklenmesi açıkça gösterilmiştir. GSI değerleri ve yüksek oranda vitellojenin üretimi, fitoestrojen içeren soya fasulyesinin balıkların endokrin sistemlerinde tahrip edici etkisi olduğunu işaret etmiştir. Balık yemlerinin hazırlanmasında, endokrin bozucu etkiye sahip olan soya fasulyesi ürünlerinin kullanımı dikkate alınması gereken bir husus olmalıdır.
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    Effect of Total Isoflavones Found in Soybean on Vitellogenin Production in Common Carp
    (Kafkas Univ, Veteriner Fakultesi Dergisi, 2009) Turker, Hakan; Bozcaarmutlu, Azra
    Soybean meal is used most extensively as a replacement to fishmeal as the main protein source in fish diets. However. there is concern about the effect of soybean-based diets on reproductive development of the fish because of the phytoestrogenic properties of soybean. The objective of the present study was to determine whether a relationship exists between the concentration of soybean extract containing total isoflavones in diet and the production of vitellogenin protein in cyprinid fish. Five different doses (0, 250, 500, 1,000, and 10,000 mg/kg based on total isoflavones content) of commercial soybean extract were tested to determine the effect of pyhtoestrogens concentration on vitellogenin synthesis in female and male carp. Cyprinius carpio L. There were no significant differences in the growth of fish between any of the groups All concentrations of soybean extract lowered male gonadosomatic index (GSI). but female GSI was increased in diets including up to 500 mg/kg soybean extract, and then decreased at higher doses. This was associated by an inhibition and induction, respectively. in plasma vitellogenin levels. Changes in GSI and vitellogenin appeared to be sensitive marker for detecting phytoestrogens exposure. Higher concentrations of isoflavones resulted in a higher amount of vitellogenin produced in both male and female fish. Our results clearly showed that exposure to phytoestrogens found in soybean extract significantly induces vitellogenin production in both males and females, in a dose-response manner. GSI and high vitellogenin production indicated that phytoestrogens found in soybean disrupt the endocrine system of fish. The endocrine disruptor effect of soybean products must be considered in fish meal preparation.
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    Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and drug metabolism and potentiation of carcinogenic activity of N-nitrosodimethylamine in kidney and lung
    (Pergamon-Elsevier Science Ltd, 2007) Arınç, Emel; Arslan, Şevki; Bozcaarmutlu, Azra; Adalı, Orhan
    There are limited number of studies regarding the influence of diabetes on the regulation of cytochrome P450s and associated drug metabolizing enzyme activities especially in extrahepatic tissues such as kidney. However, there is almost no such study in lung. Alloxan-induced diabetes did not change CYP2B4 expression as measured with immunoblot analysis and associated enzyme, benzphetamine N-demethylase, activity in rabbit kidney and lung. Induction of cytochrome P4502E1 by diabetes was identified by immunochemical detection on Western blots in the lung and kidney microsomes of rabbits. In parallel to CYP2EI induction, aniline 4-hydroxylase and p-nitrophenol hydroxylase activities were markedly increased in diabetic rabbit lung and kidney. CYP2B4 and CYP2E1 dependent drug metabolism did not show any tissue variation in diabetic rabbit. These findings are in contrast to those of rats, mice and hamster. The results of the present work, in combination with those of the previous work [Arinc, E., Arslan, S., Adali, O., 2005. Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver. Arch. Toxicol. 79, 427433], indicate the existence of species-dependent response of GYP-dependent drug metabolizing enzymes to diabetes. A procarcinogen and food contaminant, N-nitrosodimethylamine (NDMA), is converted to its carcinogenic form after it is activated with NDMA N-demethylase. In the current study, a statistically significant increase of liver, kidney and lung NDMA N-demethylase activity associated with CYP2E1 was shown in diabetic rabbit. Thus, it is expected that, the risk of nitrosamine induced carcinogenesis will be greater in liver, kidney and lung of the diabetic subjects. (c) 2006 Elsevier Ltd. All rights reserved.