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Öğe Alteration of enzyme activities and kinetic properties of GST and NQO1 with naturally occurring phenolic compounds(WALTER DE GRUYTER GMBH, 2015) Karakurt, Serdar; Sever, Melike; Celebioglu, Hasan Ufuk; Adali, OrhanObjective: Glutathione S-transferase (GST) and NAD(P)H:quinine oxidoreductase 1 (NQO1) are the enzymes important in cytoprotection and bioactivation of chemicals. This study has addressed effects of polyphenolic compounds; ellagic acid, quercetin, naringenin, resveratrol, rutin and hesperidin on rabbit liver GST and NQO1 enzyme activities. Methods: Cytosolic fractions were obtained from homogenized liver tissues of rabbit by differential centrifugation. After calculating IC50 values of individual enzymes for phenolic compounds, both Lineweaver-Burk and Dixon plots were drawn to determine the effect of phenolics on enzyme activity. Michaelis-Menten constant (K-m), maximum velocity (V-max), and inhibition constant (K-i) were calculated from Lineweaver-Burk and Dixon plots, respectively. Results: Resveratrol was found to be the most potent inhibitor for rabbit hepatic cytosolic GST activity with 75.9 +/- 2.06 mu M IC50 value while naringenin was the least potent one with IC50 value of 260 +/- 1.92 mu M. Hesperidin and quercetin were found to be the most and least potent inhibitors for NQO1 enzyme activity with IC50 values of 2.7 +/- 0.85 mu M and 13.8 +/- 0.91 mu M, respectively. Resveratrol and naringenin inhibited GST activity noncompetitively and mixed type with K-i of 6.2 mu M and 245 mu M, respectively; while both hesperidin with 0.64 mu M K-i value and quercetin with 3.5 mu M K-i value inhibited NQO1 activity in a competitive manner. Conclusion: These results indicate that phenolic compounds may modulate Phase II enzyme, GST and NQO1. Moreover, they can influence the metabolic activation of xenobiotic and toxic compounds metabolized by this enzyme.Öğe Alteration of enzyme activities and kinetic properties of GST and NQO1 with naturallyoccurring phenolic compounds(2015) Karakurt, Serdar; Sever, Melike; Celebioglu, Hasan Ufuk; Adali, OrhanAmaç: Glutatyon S-transferaz (GST) ve NAD(P)H:Kuinon Oksidoreduktaz 1 (NQO1) enzimleri kimyasal moleküllerin biyoaktivasyonunda rol alırken diğer yandan da onların zararlı etkilerine karşı koruma görevi görürler. Bu çalışma ile polifenolik bileşiklerden elajik asit, kuarsetin, naringenin, resveratrol, rutin ve hesperidinin tavşan karaciğer GST ve NQO1 enzim aktiviteleri üzerine etkileri amaçlanmıştır.Metod: Homojenize tavsan karaciğer dokusundan, diferansiyel santrifügasyon ile sitozolik fraksiyonlar elde edilmiştir. Her bir enzime ait fenolik bileşikler için IC50 değerleri hesaplandıktan sonra, fenoliklerin enzim aktiviteleri üzerine etkisini belirlemek icin Lineweaver-Burk ve Dixon grafikleri çizilmiştir. Bu grafiklerden Michaelis-Menten sabiti (Km), maksimum hız (Vmax) ve inhibisyon sabiti (Ki) hesaplanmıştır.Bulgular: Resveratrol, 75.92.06 ?M IC50 değeri ile tavsan karaciğer sitozolik GST aktivitesi için en güçlü inhibitor iken, naringenin 2601.92 ?M IC50 değeri ile en az güçlü inhibitor bulunmuştur. Hesperidin ve quersetin ise NQO1 enzimi için sırasıyla 2.70.85 ?M IC50 değeri ile en fazla ve 13.80.91 ?M IC50 değeri ile en düşük inhibitorler olarak bulunmuştur. Resveratrol ve naringenin GST aktivitesini sırasıyla 6.2 ?M Ki değeriyle yarışmasız ve 245 ?M Ki değeriyle karışık inhibisyon seklinde inhibe etmiştir. Öte yandan 0.64 ?M Kideğeri ile hesperidin ve 3.5 ?M Ki değeri ile quersetin NQO1 enzimini yarışmalı inhibisyon seklinde inhibe etmiştir.Sonuç: Bu bulgular göstermektedir ki fenolik bileşiklerin Faz II enzimlerinden GST ve NQO1'i modüle edebilir. Ayrıca, bu bileşikler bu enzimlerin metabolize ettiği ksenobiyotik ve toksik bileşiklerin metabolik aktivasyonunu etkileyebilir.Öğe Contribution of ellagic acid on the antioxidant potential of medicinal plant Epilobium hirsutum(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2016) Karakurt, Serdar; Semiz, Asli; Celik, Gurbet; Gencler-Ozkan, Ayse Mine; Sen, Alaattin; Adali, OrhanIn the present study, the possible role of ellagic acid (EA) on antioxidant potential of Epilobium hirsutum (EH) in rat liver was investigated. Wistar rats were intraperitoneally treated with 37.5 mg/kg of EH and 10 mg/kg of EA for 9 days. Effects of EH and EA on antioxidant [glutathione peroxidase (GPx) and superoxide dismutases (SOD)] and Phase II [NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs)] enzyme activities, as well as protein and mRNA expressions of those, were investigated. Polyphenolic content of EH was determined by LC-MS/MS analysis. EH and EA injection to rats resulted in a significant increase of NQO1 (3.6-fold and 4.7-fold), GPx (1.45-fold), and SOD (1.34-fold and 1.27-fold) enzyme activities, whereas total GST (46% and 57%) and its isoforms, and GST mu (57% and 72%), and GST theta (60% and 68%) activities were significantly decreased. Western-blot and qRT-PCR analysis showed that NQO1 and GPx protein and mRNA expressions were increased significantly (P < 0.0001), whereas GST mu and GST theta were significantly decreased (P < 0.0001).Öğe In vivo examination of the effects of hydroxycinnamic acid on xenobiotic metabolizing and antioxidant enzymes(INST BIOLOSKA ISTRAZIVANJA SINISA STANKOVIC, 2017) Semiz, Asli; Celik-Turgut, Gurbet; Karakurt, Serdar; Akca, Hakan; Arslan, Sevki; Adali, Orhan; Sen, AlaattinIn the last decade, hydroxycinnamic acids (HCA) have gained increasing attention from researchers due to their antioxidant potential. The aim of this study was to examine in detail the impact of dietary HCA on particular types of P450 and also selected phase II and antioxidant enzymes in Wistar rat. HCA (10 mu M/kg/day, i.p.) was administered for ten continuous days. Examination of the activities and mRNA and protein levels revealed that CYP2B, 2C6 and 3A enzyme activities were not altered significantly, with Western blot and qRT-PCR results corroborating this result. While treatment with HCA led to a significant reduction in CYP1A1/CYP1A2-associated enzyme activities, CYP1A1 protein, and mRNA levels were found to be unchanged. Aromatase (CYP19) activity, as well as protein and mRNA levels, were significantly reduced with HCA treatment. On the other hand, the NAD(P) H: quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferases (GSTs) activities were increased significantly. Also, HCA treatment significantly increased the GST-mu and GST-theta mRNA levels.Öğe Inhibitory action of Epilobium hirsutum extract and its constituent ellagic acid on drug-metabolizing enzymes(SPRINGER FRANCE, 2016) Celik, Gurbet; Semiz, Asli; Karakurt, Serdar; Gencler-Ozkan, Ayse Mine; Arslan, Sevki; Adali, Orhan; Sen, AlaattinEpilobium hirsutum (EH) is a medicinal plant for treating various diseases. Despite its wide usage, there is no available information about its potential influences on drug metabolism. The present study was undertaken to determine the in vivo effects of EH on hepatic CYP2B, CYP2C, CYP2D, and CYP3A enzymes that are primarily involved in drug metabolism. Male Wistar rats were injected intraperitoneally with EH water extract (EHWE) and ellagic acid (EA) at a daily dose of 37.5 and 20 mg/kg, respectively, for 9 days and hepatic drug-metabolizing enzymes were assessed at activity, protein and mRNA levels. Erythromycin N-demethylase activity was inhibited by 53 and 21 % in EHWE- and EA-treated rats, respectively. Benzphetamine N-demethylase and 7-benzyloxy-resorufin-O-debenzylase activities were decreased by 53 and 43 %, and 57 and 57 % in EHWE-and EA-treated rats, respectively. Moreover, protein levels of CYP2B1, CYP2C6, CYP2D2, and CYP3A1 also decreased by 55, 15, 33, and 82 % as a result of EHWE treatment of rats, respectively. Similarly, CYP2B1, CYP2C6, CYP2D2, and CYP3A1 protein levels decreased by 62, 63, 49, and 37 % with EA treatment, respectively. qRT-PCR analyses also showed that mRNA levels of these enzymes were significantly inhibited with bothEHWE and EA treatments. In conclusion, inhibition of drug clearances leading to drug toxicity because of the lowered activity and expression of drug-metabolizing enzymes might be observed in the people who used EH as complementary herbal remedy that might be contributed by its EA content.Öğe Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes(BENTHAM SCIENCE PUBL LTD, 2016) Karakurt, Serdar; Adali, OrhanThe aim of this study was to investigate the effects of plant phenolic compound tannic acid (TA) on proliferative, metastatic, invasive properties of prostate cancer (PCa) cells; PC-3 and LNCaP, as well as drug metabolizing and antioxidant enzymes. Characterization of TA was done by using FT-IR and NMR. TA dose dependently inhibited the proliferation of PC-3 and LNCaP cells with IC50 values 35.3 mu M and 29.1 mu M, respectively. Wound healing assay showed that TA significantly inhibited (92.7%) migration of PCa cells (p<0.0001). In addition, TA was found to have anti-invasive potential on PC-3 cells and it inhibited (80.9%, p<0.0001) invasion of PC-3 cells into matrigel. Only 17.8% of PC-3 cells can form colony in the 0.7% agarose after treatment of cells with TA at the IC50 value concentration. Furthermore, flow cytometry analyses with Annexin V-APC and 7-AAD staining demonstrated that TA increases early apoptosis rate of PC-3 cells by 25.8% and LNCaP cells by 20.9%. Besides, Western blot and qRT-PCR analyses also demonstrated that TA regulates protein and mRNA expressions of CYP17A1, CYP3A4, CYP2B6, NQO1, GSTM1 and GSTP1 enzymes. The results obtained from this study show that TA might be a good candidate for combinational therapy and highly effective strategic molecule for reducing the occurrence of PCa.