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Cytochrome P450s are very large and diverse superfamily of hemoproteins found in all domains of life and diverse array of compounds can influence the relative concentrations and/or activities of P450s. Expression of P450s is modulated not only by exposure to various chemicals, but also by some pathophysiological conditions such as diabetes, hypertension and obesity. Six different Cytochrome P450 isoforms namely; 1A1, 2A1, 2E1, 2C11, 3A1, 4A1 were quantified by quantitative Real Time PCR to assess the relative expressions of CYPs mRNA in control and diabetic rat liver tissues. At the same time, effects of resveratrol (RSV) on these isoforms were evaluated. According to results, diabetes enhanced the CYP1A1, CYP2E1 and CYP3A1 gene expression and RSV reduced to these increments toward the control values. Furthermore, while CYP2C11 and CYP4A1 expressions were found to be reduced by diabetes, application of RSV decreased these isoforms’expressions further. Additionally, diabetes and RSV treatment did not alter the CYP2A1&2 expressions significantly.As a result, expressions of cytochrome P450 were altered not only by diabetes but also by exposure to antioxidants such as resveratrol and levels of expressions of each isoforms are important factors determining the biological consequences of xenobiotics and antioxidant defense systems in diabetes

WOS:000843961900001 In this study, antioxidant, antibacterial, cytotoxic, and antioxidant enzyme inhibitory properties of the 7,8-dihydroxy-3-(4-methylphenyl) coumarin were investigated. Its free radical scavenging activity, total antioxidant capacity, and reducing power were as high as standard antioxidants, namely gallic acid and Trolox. It also demonstrated antibacterial effects on tested microorganisms and cytotoxic activity on breast cancer (MCF-7) cells, even though it was non-toxic to hepatocellular carcinoma (HepG2) cells (IC50 for HepG2: 0.553 mM; IC50 for MCF-7: 0.040 mM). 7,8-Dihydroxy-3-(4-methylphenyl) coumarin inhibited catalase enzyme in a dose-dependent manner (IC50 0.12 mM), and the decrease in V-max and K-m values of catalase suggests a mixed-type inhibitory mechanism. Glutathione-S-transferase activities were also suppressed with IC50 3.7 mM for 1-chloro-2,4-dinitrobenzene- and 7.5 mM for glutathione-dependent glutathione-S-transferase activities. While the changes in kinetic parameters indicated a possible competition between 1-chloro-2,4-dinitrobenzene-substrate for glutathione-S-transferase activity, glutathione-dependent glutathione-S-transferase activity is consistent with the mixedtype inhibition model. These results indicated the high antioxidant, antimicrobial, and cytotoxic potential of 7,8-dihydroxy3-(4-methylphenyl) coumarin and inhibitory effects over main antioxidant and detoxification enzymes that might induce oxidative stress and xenobiotic induced apoptosis in cancer cells which would prevent oncogenesis and tumor progression in the liver and breast cancer.

The use of medicinal plants and secondary metabolites increases in treating numerous diseases such as hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death worldwide. Oxidative stress contributes to the development of liver cancer, and promoting antioxidant systems might provide better insights for the treatment. In the present study, the antioxidant potential of Pseudevernia furfuracea (L.) Zopf lichen species were investigated. Besides, effects of major secondary metabolites, olivetoric acid (OA) and physodic acid (PA), which were isolated from P. furfuracea, on hepatic gene expressions of antioxidant enzymes, were evaluated in both cancerous (HepG2) and healthy (THLE2) human liver cells. According to the results, the total phenolic content of P. furfuracea was 71.52 µg/mg and 8.16 µg/mg gallic acid equivalent for ethanolic and aqueous extracts, respectively. Likewise, β-carotene and lycopene contents were also higher in ethanolic extracts. In line with these antioxidant ingredients, DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity of ethanol extract (IC50: 158.79 mg/L) was remarkably high as compared with its aqueous extracts (IC50: 630.33 mg/L). OA and PA strongly augment all antioxidant enzymes’ gene expressions in HepG2 cells, while only gpx expression was upregulated in healthy THLE2 cells. Conversely, these two metabolites suppress cat, sod1, and sod2 expressions in THLE2 cells. These results together suggest that P. furfuracea not only has high antioxidant potential, but its secondary metabolites might also reduce oxidative stress in cancer cells by upregulating antioxidant enzymes, which would prevent oncogenesis and tumor progression in liver cancer., Dünyada kansere bağlı ölümlerin önde gelen nedenlerinden biri olan hepatosellüler karsinom (HCC) gibi çok sayıda hastalığın tedavisinde tıbbi bitkilerin ve sekonder metabolitlerin kullanımı artmaktadır. Oksidatif stres, karaciğer kanseri gelişimine katkıda bulunur ve antioksidan sistemlerin teşvik edilmesi, tedavi için daha iyi bilgiler sağlayabilir. Bu çalışmada, Pseudevernia furfuracea (L.) Zopf likeninin antioksidan potansiyeli araştırılıştır. Ayrıca, P.furfuracea'dan izole edilen ana sekonder metabolitler olan olivetorik asit (OA) ve fisodik asitin (PA) hepatik antioksidan enzimlerin gen ekspresyonları üzerindeki etkileri hem kanserli (HepG2) hem de sağlıklı (THLE2) insan karaciğer hücrelerinde değerlendirilmiştir. Sonuçlara göre, P. furfuracea'nın toplam fenolik içeriği etanolik ve sulu ekstraktlar için sırasıyla 71.52 µg/mg ve 8.16 µg/mg gallik asit eşdeğeri bulunmuştur. Aynı şekilde β-karoten ve likopen içerikleri de etanolik ekstraktlarda daha yüksek olarak belirlenmiştir. Bu antioksidan bileşenlerle uyumlu olarak, etanol özütünün DPPH (2,2-difenil-1-pikrilhidrazil) radikal süpürme aktivitesi (IC50: 158.79 mg/L), sulu ekstraktlar (IC50: 630.33 mg/L) ile karşılaştırıldığında oldukça yüksektir. OA ve PA, HepG2 hücrelerinde tüm antioksidan enzimlerin gen ifade düzeylerini arttırırken, sağlıklı THLE2 hücrelerinde ise sadece gpx ekspresyonu yukarı yönde regüle olmuştur. Bundan farklı olarak, her iki metabolit de THLE2 hücrelerinde cat, sod1 ve sod2 ekspresyonlarını baskılamıştır. Bu sonuçlar P. furfuracea'nın sadece yüksek antioksidan potansiyeline sahip olmadığını, aynı zamanda sekonder metabolitlerinin de karaciğer kanserinde onkogenezi ve tümör ilerlemesini önleyecek antioksidan enzimleri yukarı regüle ederek kanser hücrelerinde oksidatif stresi azaltabileceğini göstermektedir.

Resveratrol, mainly found in grapes, blueberries, raspberries, mulberries, and peanuts, is a naturally synthesized polyphenol that protects against several pathological issues. Increased oxidative stress in cancer cells and suppressed cellular antioxidant systems have been investigated and therefore herbal antioxidants could be used as an auxiliary substance in the treatment of several types of cancer. In this study, we inspected the effects of resveratrol, a powerful antioxidant, in the gene expression and activities of antioxidant enzymes in healthy and cancerous liver cells. After the liver cancer cells (HepG2) and healthy hepatocytes (THLE2) were treated with resveratrol at different doses (25-, 50-, 75- µM) for 48-hours, the gene expression levels of antioxidant enzymes were measured by qRT-PCR and their activities were measured spectrophotometrically. The results showed the suppression of all antioxidant enzymes in the THLE2 cells at all doses of resveratrol but conversely upregulation of those in HepG2 cells. The reduction in gene expression in healthy cells was in line with the suppression of enzymatic activities of catalase and glutathione S-transferase, however, the activity changes in cancer cells were not significant. This differential regulation of antioxidant enzyme systems in healthy and cancerous hepatocytes demonstrates the stimulation of antioxidant enzymes in cancer cells as a protective function against oxidative damage, while decreased expression in healthy cells signifies the reduction of requirement for antioxidants, conversely. Therefore, resveratrol might be effective in cancer treatment through affecting the molecular mechanisms that can reduce cellular stress by activating antioxidant enzymes in cancer cells. Üzüm, yaban mersini, ahududu, dut ve yer fıstığı gibi bitkilerde bulunan resveratrol, çeşitli patolojik sorunlara karşı koruma sağlayan doğal olarak sentezlenmiş bir polifenoldür. Kanser hücrelerinde oksidatif stresin artışı ve hücresel antioksidan sistemlerin baskılanması belirlenmiş olup, bitkisel antioksidanların çeşitli kanser türlerinin tedavisinde yardımcı madde olarak kullanılabileceği öngörülmektedir. Bu çalışmada, güçlü bir antioksidan olan resveratrolün sağlıklı ve kanserli karaciğer hücrelerinde antioksidan enzimlerin gen ekspresyonu ve aktiviteleri üzerindeki etkileri araştırılmıştır. Karaciğer kanseri hücreleri (HepG2) ve sağlıklı hepatositler (THLE2) resveratrol ile farklı dozlarda (25-, 50-, 75- µM) 48 saat süreyle muamele edildikten sonra antioksidan enzimlerin gen ekspresyon seviyeleri qRT-PCR ile, aktiviteleri ise spektrofotometrik olarak ölçülmüştür. Sonuçlar, THLE2 hücrelerindeki tüm antioksidan enzimlerin resveratrolün tüm dozlarında baskılandığını, ancak bunun tersine HepG2 hücrelerinde antioksidan enzimlerin yukarı regülasyonunu göstermiştir. Sağlıklı hücrelerde görülen gen ekspresyonundaki azalma, katalaz ve glutatyon S-transferazın enzimatik aktivitelerinin baskılanmasıyla paralel değiştiği, ancak kanser hücresindeki aktivite değişikliklerinin anlamlı olmadığı belirlenmiştir. Sağlıklı ve kanserli hepatositlerde antioksidan enzim sistemlerinin farklı olarak düzenlemesi, kanser hücrelerinde antioksidan enzimlerin oksidatif hasara karşı koruyucu bir işlev olarak uyarılmasını gösterirken, sağlıklı hücrelerde azalmış ekspresyon, tersine antioksidan ihtiyacının azalmasına işaret etmektedir. Bu nedenle resveratrol, kanser hücrelerinde antioksidan enzimleri aktive ederek hücresel stresi azaltabilecek moleküler mekanizmaları etkileyerek kanser tedavisinde etkili olabilir.

Paper description: Dietary high-fructose causes metabolic disorder and augments the risk of chronic kidney diseases most probably due to oxidative stress. Renal superoxide dismutases are suppressed while catalase is upregulated in fructose-fed rats. Lactobacillus helveticus and Lactobacillus plantarum alleviate dietary fructose-induced changes in biochemical markers of blood and renal antioxidant enzymes . L actobacillus helveticus and L actobacillus plantarum might have a positive influence on renal antioxidant capacity in the dietary fructose-induced metabolic disorder. Abstract: High dietary fructose intake causes a metabolic disorder and augments the risk of chronic kidney disease most likely due to oxidative stress. Probiotics could have antioxidant, antiinflammatory and immunoregulatory properties. The present study examined the influence of Lactobacillus helveticus and Lactobacillus plantarum supplementation on dietary fructose-induced metabolic changes and renal antioxidant/oxidant status of rats. Male Wistar rats were divided into four groups as follows: control; fructose; fructose plus L. helveticus ; fructose plus L. plantarum . Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. The probiotic supplementation was applied by gastric gavage once a day for six weeks. Several metabolic parameters in the plasma, gene and protein expressions of the main antioxidant enzymes in renal tissues of rats were measured. Dietary fructose-induced elevations in plasma insulin, triglyceride, VLDL, creatinine as well as renal urea levels were alleviated after treatment with L. helveticus and L. plantarum . Moreover, L. helveticus and L. plantarum supplementation recovered the changes in renal protein expression level of SOD1, SOD2 and CAT. In conclusion, supplementation with L. helveticus and L. plantarum has an improving effect on specific metabolic parameters and renal antioxidative enzymes in a fructose-induced metabolic disorder. https://doi.org/10.2298/ABS190123008K Received: January 23, 2019; Revised: February 20, 2019; Accepted: February 21, 2019; Published online: February 26, 2019 How to cite this article: Korkmaz OA, Sadi G, Kocabas A, Yildirim OG, Sumlu E, Koca HB, Nalbantoglu B, Pektas MB, Akar F. Lactobacillus helveticus and Lactobacillus plantarum modulate renal antioxidant status in a rat model of fructose-induced metabolic syndrome. Arch Biol Sci. 2019;71(2):265-73.

WOS:000729121600001 Background and Aims: The dietary high-fructose intake might be a risk factor for several metabolic diseases. Kefir, a fermented milk product, has been proposed to have beneficial health effects. In this study, we aimed to investigate the effects of fructose consumption and kefir supplementation on the lipogenesis-related genes including angiopoietin-like protein 8 (angptl8), phosphoinositide 3-kinase (pi3k), mammalian target of rapamycin (mtor), and peroxisome proliferator-activated receptor gamma (ppar gamma) as well as inflammatory factors in the adipose tissue to provide new mechanistic insights into lipogenesis. Methods: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administered by gastric gavage once a day during the final six weeks. Results: There was an upregulation of angptl8 mRNA expression in adipose tissue of rats given fructose. However, expressions of pi3k, mtor, and ppar gamma mRNAs were impaired in the adipose tissue. The increased interleukin (IL)-1 beta levels, but decreased IL-10, were also measured. There was no change in expressions of sirtuin1 (sirt1) and nuclear factor erythroid 2-related factor 2 (nrf2). Kefir supplementation suppressed expression of angptl8, but increased pi3k and mtor in the adipose tissue of high-fructose-fed rats. Conclusion: Activation of gene expression of angptl8, together with the suppression of pi3k, mtor, and ppar gamma, showed that there was an inverse association between these lipogenic genes in the adipose tissue of rats fed with high-fructose. Kefir supplementation has modulatory effects on fructose-induced changes except for ppar gamma expression. These findings showed that dietary fructose and kefir might reciprocally affect the lipogenesis-related genes in the adipose tissue. This study was supported by Gazi University Research Fund with the grant number BAP 02/2018-14.

WOS:000605357000003 Background and Aims: The influence of a high-fructose diet and probiotics on the mate reproductive system and the testicular apoptotic pathway has been poorly documented. In this study, we aimed to investigate the influence of Lactobacillus plantarum and Lactobacillus helveticus supplementation on apoptotic factors such as sirtuin1, caspase3 and bcl-2 on the testicular tissue of high-fructose-fed rats. Methods: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Gene expressions were established by real-time PCR. Protein levels were determined by Western blot analysis. Results: Fructose consumption did not change mRNA expression of SIRT1, but did resulted in a decreased protein level. Dietary fructose reduced bcl-2 mRNA and protein expressions, whereas no changes were observed in the gene and protein expression levels of factor caspase-3. Both Lactobacillus supplementations increased SIRT1 protein expression without changing the mRNA levels in fructose-fed rats. The supplementations with both probiotics produced a significant downregulation on caspase3 mRNA and protein levels. Bcl-2 proetin level increases with both probiotics supplementation white, mRNA level did not show difference in L.plantarum, but increased in L. helveticus supplementation. Conclusion: Treatments with L.plantarum and L.helveticus can reduce testicular apoptosis induced by dietary high-fructose in rats via suppressing caspase3 and promoting sirt1 and bcl-2 protein expressions. This work was supported by the Gazi University Research Fund under Grant [BAP 02/2017-20].

WOS:000492371400038 PubMed:31400747 Synthesis of the 2-amino-4-phenyl-6- (isocoumarin-3-yl) -3-cyanopyridine (APICP) containing both isocoumarin and pyridine ring in its structure was carried out, and this compound was characterized by ATR-FTIR, H-1 NMR, and C-13 NMR spectral techniques. A fluorescence sensor determining Hg2+ and Fe3+ ions in DMSO/HEPES buffer solution (9/1 v/v, 5 mu M, pH 7.0) was developed using the synthesized compound, and the detection limits of the sensor with exquisite selectivity were calculated as 8.12 nM and 5.51 nM for Hg2+ and Fe3+ ions, respectively. Jobs plot method was used to determine the stoichiometry of APICP-Hg2+/Fe3+ complexes as 2:1 and FT-IR and ESI-MS methods confirmed the results. Besides, cell growth inhibitory potentials of the sensor over HepG2 cells and in vivo fluorescent cell imaging experiments were conducted. Findings revealed the relatively low cytotoxic effects of the synthesized sensor (IC50: 0.541 +/- 0.039 mM), and it could be utilized as an intracellular imaging agent for the determination of Fe3+ and Hg2+ ions in biological systems. (c) 2019 Elsevier B.V. All rights reserved. KMU Scientific Research Project Center [30-M-16] The authors are grateful to the KMU Scientific Research Project Center for their support with the project numbers 30-M-16 and to provide the Gaussian 09W and Gaussview 5.0.8 programs.

Phase I-II detoxification and antioxidant enzymes are responsible for the detoxification and elimination of activated carcinogens, acting as important biomarkers for chemoprevention. Among them, cytochrome P450s plays a prominent role in the metabolic activation of xenobiotics. The herb Salicornia freitagii ( SF ) (Amaranthaceae) is known for its anticancer, antioxidant, antidiabetic and antiinflammatory activities. In this study, we determined the bioactive phenolics in the SF methanol extract and investigated its antiproliferative potential in HT-29 human colon cancer cells. We also investigated the modulation of some phase I and II enzyme (CYP 1A1, 1A2, 2E1, GSTP1 and GPx) mRNA expression and enzymatic activities by the SF extract and its major bioactive phenolic compounds. LC/MS-MS analysis showed that the main phenolic compounds of the methanolic SF extract are vanillic acid (48 µg/100g) and p-coumaric acid (10.8 µg/100g). SF extract, vanillic acid and p-coumaric acid exhibited high antiproliferative activities in HT-29 cells, with IC 50 values of 81.79µg/mL, 98.8 µM and 221.6 µM, respectively. The mRNA expression levels of CYP1A2 and CYP2E1 were decreased, while those of GSTP1 and GPx in HT-29 cells were increased after application of either the SF extract or vanillic acid. The SF extract by itself also increased the activities of GPx and GSTP1 enzymes 1.68- and 1.49-fold, respectively. Our data indicate that the SF extract and its major bioactive compound, vanillic acid, could exert a modulatory effect on the expression of enzymes that are involved in xenobiotic activation and detoxification pathways in the gastrointestinal tract. For this reason, SF can be considered as a natural source of chemopreventive agents. https://doi.org/10.2298/ABS160825118A Received: August 25, 2016; Revised: October 8, 2016; Accepted: October 13, 2016; Published online: November 3, 2016 How to cite: Altay A, Irtem Kartal D, Sadi G, Guray T, Yaprak AE. Modulation of mRNA expression and activities of xenobiotic metabolizing enzymes, CYP1A1, CYP1A2, CYP2E1, GPx and GSTP1 by the Salicornia freitagii extract in HT-29 human colon cancer cells. Arc Biol Sci. 2017;69(3):439-48.

Bu çalışmada yeni sentezlenen karbonat iyonu sensörü DHMC, Hg2+ ve Fe3+ sensörü APICP ve tiyol grubu sensörü PDI/Arg bileşiklerinin antioksidan, antibakteriyel ve sitotoksik etkileri araştırılmıştır. Ayrıca bu bileşiklerin antioksidan enzimler üzerine etkileri ve canlı hücre sistemlerinde çeşitli iyonların ve fonksiyonel grupların tanımlanmasında kullanılabilirlikleri araştırılmıştır. İncelen üç bileşik içerisinde antioksidan özellikleri en yüksek olan bileşiğin DHMC olduğu, DPPH radikal süpürücü etkiler ve toplam antioksidan kapasite sonuçlarından anlaşılmaktadır. APICP bileşiğinin toplam antioksidan kapasitesinin DHMC bileşiği ile benzerlik gösterdiği, PDI/Arg molekülünün ise yüksek ölçüde indirgeme potansiyeline sahip olduğu bulunmuştur. Antimikrobiyel etkilerinin incelendiği çalışmalarda DHMC bileşiğinin test edilen mikroorganizmaların hepsi üzerinde kuvvetli etkisi olduğu, APICP bileşiğinin ise S.aureus, B.subtilis ve Salmonella gibi mikroorganizmalar üzerinde antibakteriyel etkiye sahip olduğu belirlenmiştir. Gerçekleştirilen enzim kinetiği çalışmaları, DHMC, APICP ve PDI/Arg bileşiklerinin CAT enzimini karışık inhibisyon mekanizmasıyla doz bağımlı bir şekilde baskıladığını göstermiştir. Ayrıca, DHMC ve APICP bileşiklerinin CDNB bağımlı GST enzim aktivitesinde birer yarışmalı inhibitör, PDI/Arg bileşiğinin ise yarışmasız (non-competatif) inhibitör olduğu belirlenmiştir. İncelenen bileşiklerin hepsi, bütün konsantrasyonlarında GSH bağımlı GST aktivitesi için Vmax değerini azaltırken, görece GSH Km değerini arttırmıştır. Bu sonuçlar üç bileşiğin de GSH bağımlı GST aktivitesini karışık tip yarışmasız inhibisyon mekanizması (uncompetatif) ile baskıladığını göstermektedir. HepG2 ve MCF-7 hücreleri üzerine gerçekleştirilen sitotoksisite çalışmalarında PDI/Arg bileşiğinin oldukça yüksek sitotoksik etki (HepG2 için IC50:0,307 mM; MCF-7 için IC50: 0,016 mM) gösterdiği bulunmuştur. Çalışma kapsamında ayrıca biyosensör olarak kullanılabilecek bileşiklerin hücre içerisindeki çeşitli iyonların ve fonksiyonel grupların in vivo tayininde kullanılabilme potansiyelleri floresan hücre görüntüleme çalışmalarıyla ilk defa ortaya çıkarılmıştır. In this study, antioxidant, antibacterial and cytotoxic properties of newly synthesized carbonate ion sensor DHMC, Hg2+ and Fe3+ sensors and thiol group sensors PDI/Arg compounds were investigated. In addition, the effects of these compounds on antioxidant enzymes and their utility in the identification of various ions and functional groups in living cell systems were determined. DHMC has the highest antioxidant properties among the three compounds examined according to DPPH radical scavenging and total antioxidant capacity results. The total antioxidant capacity of the APICP compound was found to be similar to that of the DHMC. Besides PDI/Arg molecule had a high reduction potential among the three compounds. In studies investigating antimicrobial effects, DHMC has a strong effect on all microorganisms tested, and APICP has an antibacterial effect on S. aureus, B. subtilis and Salmonella. Enzyme kinetics studies have shown that DHMC, APICP and PDI/Arg compounds suppress CAT enzyme in a dose-dependent manner with mixed inhibition mechanism. In addition, DHMC and APICP compounds were found to be competitive inhibitors of CDNB-dependent GST enzyme activity and PDI/Arg were non-competitive inhibitors. All of the compounds examined decreased Vmax for GSH-dependent GST activity at all concentrations, while increasing relative Km value for GSH. These results show that all three compounds suppress GSH-dependent GST activity by a mixed-type uncompetitive inhibition mechanism. Cytotoxicity studies on HepG2 and MCF-7 cells showed that the PDI/Arg compound exhibited a very high cytotoxic effect (IC50: 0.330 mM for HepG2; IC50: 0.016 mM for MCF-7). Additionally, the potential of the biosensor compounds for in vivo determination of various ions and functional groups in the cell has been revealed for the first time by fluorescent cell imaging studies. 91

Background and Objectives: The excess consumption of fructose in the diet may cause metabolic syndrome, which is associated with an increased risk of kidney disease. There is limited data on probiotic treatment in high-fructose-induced metabolic syndrome. The present study aims to investigate whether the supplementation of Lactobacillus plantarum (L. plantarum) and Lactobacillus helveticus (L. helveticus) could provide an improving effect on the renal insulin signaling effectors, inflammatory parameters, and glucose transporters in fructose-fed rats. Materials and Methods: The model of metabolic syndrome in male Wistar rats was produced by fructose, which was given as 20% solution in drinking water for 15 weeks. L. plantarum and L. helveticus supplementations were given by gastric gavage from 10 to 15 weeks of age. Results: High-fructose consumption in rats reduced renal protein expressions of insulin receptor substrate (IRS)-1, protein kinase B (AKT), and endothelial nitric oxide synthase (eNOS), which were improved by L. plantarum and partially by L. helveticus supplementations. Dietary fructose-induced elevations in renal tissue levels of tumor necrosis factor &alpha, (TNF-&alpha, ), interleukin (IL)-1&beta, IL-6, and IL-10, as well as expression of IL-6 mRNA, were attenuated, especially in L. plantarum treated rats. The increased renal expression of sodium-glucose cotransporter-2 (SGLT2), but not that of glucose transporter type-5 (GLUT5), was suppressed by the treatment with L. plantarum. Conclusion: Suppression in insulin signaling pathway together with the induction of inflammatory markers and upregulation of SGLT2 in fructose-fed rats were improved by L. plantarum supplementation. These findings may offer a new approach to the management of renal dysregulation induced by dietary high-fructose.

Paper description: Changes in dynamic thiol/disulfide homeostasis in generalized vitiligo was confirmed. Native and total thiol contents were significantly lower in vitiligo patients. Disulfide/native thiol and disulfide/total thiol ratios were higher in vitiligo patients. Thiol/disulfide homeostasis was shifted toward disulfide formation. Progressivity of the disease strongly regulated the thiol/disulfide homeostasis. Abstract: Vitiligo is a multifactorial disorder commonly associated with hypo-/depigmentation in the skin and may influence both children and adults psychologically because of the notable leopard-skin-like appearance. This study was designed to investigate the thiol/disulfide homeostasis in patients with generalized vitiligo and to determine its relationship with some of the demographical characteristics. Seventy-six generalized vitiligo patients and 67 healthy individuals were included in the study. Blood serum native thiol, disulfide and total thiol concentrations, together with some hematological parameters, were determined. Results demonstrated that native and total thiol contents, and their ratios, were significantly lower in vitiligo patients. Disulfide/native thiol and disulfide/total thiol ratios were significantly higher in the patient group. Progressivity of the disease strongly regulated the thiol/disulfide homeostasis in such a way that active vitiligo patients had reduced native and total thiol levels but increased disulfide/native thiol and disulfide/total thiol ratios. Moreover, there was a statistically significant negative correlation between both duration of the vitiligo and native and total thiol contents. As these results clearly demonstrated that thiol/disulfide homeostasis was shifted toward disulfide formation in patients with generalized vitiligo, determining the dynamic nature of thiol/disulfide homeostasis can be used to monitor disease progression. https://doi.org/10.2298/ABS181003047P Received: October 3, 2018; Revised: October 8, 2018; Accepted: October 9, 2018; Published online: October 10, 2018 How to cite this article: Pektas G, Pektas SD, Oztekin A, Oztekin C, Neselioglu S, Erel O, Sadi G. Dynamic thiol/disulfide homeostasis in serum of patients with generalized vitiligo. Arch Biol Sci. 2019;71(1):55-62.

Bu çalışmada, Staurogyne repens (Nees) Kuntze'in doku kültürü teknikleri ile çoklu ve hızlı üretimi hedeflenmiştir. S. repens'in yüzey sterilizasyonu için farklı süre ve konsantrasyonlarda hidrojen peroksit (H2O2) kullanılmıştır. Maksimum steril-canlı eksplantlar, 20 dakikalık uygulama süresi ile %5,5'lik H2O2'den elde edilmiştir. Steril bitkilerden boğum eksplantları izole edilmiş ve in vitro çoğaltım çalışmalarında kullanılmıştır. Boğum eksplantları sitokininleri (BAP, TDZ ve KIN) ve oksini (IAA) farklı dozlarda ve kombinasyonlarda içeren Murashige ve Skoog (MS) temel besin ortamında altı hafta süre ile kültüre alınmıştır. Eksplant başına maksimum sürgün sayısı (16,11 adet) 1,25 mg/LBAP içeren MS besin ortamında elde edilmiştir. En uzun sürgünler (2,82 cm) 1,50 mg/L KIN eklenmiş kültür ortamında tespit edilmiştir. Rejenere sürgünlerin in vitro köklendirilmesi için kültür ortamlarına farklı konsantrasyonlarda (0,25-1,00 mg/L) IAA ve NAA ilave edilmiştir. Sürgün başına en fazla kök sayısı (14,88 adet) ve en uzun kökler (1,22 cm) 0,25 mg/L IAA eklenmiş MS besin ortamında kaydedilmiştir. Köklendirilen sürgünler dış koşullara alıştırılması için akvaryuma aktarılmıştır. Dört hafta sonunda bitkilerin akvaryum şartlarına başarıyla adapte olduğu gözlenmiştir. Bu tez çalışması, akvaryum bitkisi S. repens'in doku kültürüyle çoklu ve hızlı üretimini sunmaktadır. Bu çalışma sonuçları ileride bu bitkinin ticari amaçlı üretimine yardımcı olabilir. In this study, multiple and rapid propagations of Staurogyne repens (Nees) Kuntze by tissue culture techniques was aimed. Hydrogen peroxide (H2O2) was used at different time periods and concentrations for surface sterilization of S. repens. Maximum sterile and alive explants were obtained from 5.5% H2O2 with 20 min application time. Nodal explants were isolated from the sterile plants and used for in vitro propagation studies. The nodal explants were cultured in Murashige and Skoog (MS) nutrient medium containing cytokinins (BAP, TDZ and KIN) and auxin (IAA) in different doses and combinations for six weeks. The maximum number of shoots per explant (16.11) was obtained in MS nutrient medium containing 1.25 mg/L BAP. The longest shoots (2.82 cm) were detected in culture medium supplemented with 1.50 mg/L KIN. IAA and NAA were added to the culture media at different concentrations (0.25-1.00 mg/L) for in vitro rooting of the regenerated shoots. Maximum number of roots per shoot (14.88) and the longest roots (1.22 cm) were recorded in MS nutrient medium supplemented with 0.25 mg/L IAA. Rooted shoots were transferred to the aquarium to acclimate them to the external conditions. After four weeks, the plants were successfully adapted to the aquarium conditions. The results of this study mignht be helpful in the commercial production of this plant in the future. 63

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants (cat, sod, gpx, and gst) and the components of the insulin signaling pathway (insulin Rβ, irs-1, pi3k, akt, mtor) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups, (1) control/vehicle, (2) control/20 mg/kg resveratrol, (3) diabetic/vehicle, (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes’ gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nfκb. Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components.

The study presents first report of Agrobacterium mediated genetic transformation in Rice paddy herb (Linmophila aromatica). A. tumefaciens strain C58C1 harboring pBin19 Plasmid containing β-glucuronidase (GUS) and neomycin phosphotransferase II (nptII) gene, under the control of 35S promoter and NOS terminator was used. Shoot tip explants were inoculated for 30 min followed by co-cultivation for 72 h and selected on agar semi solidified MS medium containing 100 mg/l Kanamycin and 1.0 mg/l BA; whereas total number of 78 putative transgenic shoots were obtained. The shoots were rooted on MS medium containing 1.0 mg/l IBA and 100 mg/l Kanamycin where 43 plants survived and rooted. Expression of GUS gene in the putative transgenics was confirmed by histochemical GUS assay. Visible localised gus expression was noted in a few cells and callus tissues of 4 plantlets that were photographed using compound light microscope.

Diabetes mellitus is a chronic inflammatory disease characterized by high blood glucose levels due to the absence of secretion of insulin or its inefficient use in the body. In this study, we investigated how resveratrol administration affects the renal functions and pro-inflammatory signaling pathway components in streptozotocin-induced diabetes in male Wistar rats. Rats were randomly divided into four groups: (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20 mg/kg resveratrol. In addition to renal glucose, lipid, angiopoietin-1 (ANG-1), asymmetric dimethylarginine (ADMA), erythropoietin (EPO), malondialdehyde (MDA) and neutrophil gelatinase-associated lipocalin (NGAL) content, the gene expressions of pro-inflammatory markers, including inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), nuclear factor (erythroid-derived 2) like-2 (Nrf2), and the protein contents of interleukins-1β,6,8 (IL-1β,6,8) and tumor necrosis factor-α (TNF-α) were analyzed using qRT-PCR and ELISA, respectively. The rats in the diabetes group demonstrated significantly lower terminal body weight and renal ANG-1, but significantly higher renal glucose, cholesterol, triglyceride, ADMA and MDA concentrations. Diabetes triggered inflammation in kidney tissues, reflected as an increase in NGAL level. The renal inflammation observed in the diabetes group was associated with significant upregulation of components of the pro-inflammatory pathway, iNOS, NF-κB, Nrf2, IL-1β, IL-6, IL-8 and TNF-α. To some extent, resveratrol administration reversed the diabetes-induced changes in renal tissues, suggesting that resveratrol partially protected from diabetes-induced renal failure due to its restorative activities in tissue inflammation. DOI: 10.2298/ABS151105031K Key words: Diabetes; resveratrol; inflammation; kidney; NGAL Received: November 5, 2015; Revised: November 12, 2015; Accepted: November 12, 2015; Published online: April 1, 2016 How to cite this article: Koca Halit B., Pektas Mehmet B., Koca Selcen, Pektas Gokhan, Sadi Gokhan. Diabetes-induced renal failure is associated with tissue inflammation and neutrophil gelatinase-associated lipocalin: Effects of resveratrol. Arch Biol Sci. 2016;68(4):747-52.

Craterellus cornucopioides (L.) Pers which is alsoknown as trumpet of death or horn of plenty, is a wild edible macrofungus. Thisstudy was conducted to elucidate the potential health beneficial properties of C. cornucopioides. Bioactive ingredients(phenolics, flavonoids, β-carotene and lycopene) and DPPH radical scavengingactivities were determined. Additionally, cell growth inhibitory effects on HepG2 cells togetherwith some bacteria were evaluated. Accordingly, water and methanol extractscontains 37.71±1.42 μg/mg and 13.78±1.60 μg/mg phenolic contents, respectively.Similarly, methanolic extracts have higher β-caroten and lycopene content ascompared to aqueous extracts.In parallel with these antioxidants, methanolic extracts have also higher DPPHscavenging activity (IC50: 5.26±0.67 mg/ml). Besides, water extractshave higher flavonoid contents (2.13±0.06 μg/mg) then the methanolicextracts. C. cornucopioides hasalso an important cell growth inhibitory effects on HepG2 cell (IC50:18.41±1.10 mg/ml for aqueous extracts and IC50: 3.14±1.07 mg/ml formethanolic extracts). Moreover, both extracts were effective on six differentbacteria tested. As a result, this study indicates that C. cornucopioides could reduce thecellular oxidative stress because of its high antioxidant ingredients, inhibitthe growth of pathogen microrganisms and have some degree of cell growthinhibitory potential at least to the HepG2 cells.Pers which is (L.) Craterellus cornucopioides, Ölüm trompetiveya bolluk boynuzu olarak da bilinen Craterelluscornucopioides (L.) Pers, yenilebilir bir makrofungustur. Bu çalışma Craterellus cornucopioides (L.) Pers mantarınınsağlık açısından yararlı özelliklerini açığa çıkarmak amacıyla yapılmıştır. Çalışmadailgili mantarın biyoaktif içerikleri (fenolikler, flavonoidler, β-karoten velikopen) ve DPPH radikal süpürücü aktiviteleri belirlenmiştir. Ek olarak, HepG2hücreleri ve bazı bakteri türleri üzrine hücre büyümesini baskılayıcı etkilerideğerlendirilmiştir. Buna göre, su ve metanol ekstraktları sırasıyla 37.71±1.42μg/mg ve 13.78±1.60 μg/mg fenolik içeriğe sahiptir. Benzer şekilde, metanolekstraktları sulu ekstrelere kıyasla daha yüksek β-karoten ve likopen içeriğinesahiptir. Bu antioksidanlara paralel olarak, metanol ekstraktları da DPPHsüpürme aktivitesine daha fazla sahiptir (ICso: 5.26±0.67 mg/ml). Ayrıca su ekstraktları,metanol ekstraklarına göre daha yüksek flavonoid içeriğine (2.13±0.06 μg/mg)sahiptir. C. cornucopioides, HepG2hücresi üzerinde de önemli bir hücre büyümesi engelleyici etkiye sahiptir (IC50:su ekstratları için 18.41±1.10 mg/ml ve metanol ektraktları için IC50:3.14±1.07 mg/ml). Buna ek olarak, her iki ekstrakt da test edilen altı farklıbakteri türü üzeine etkili olmuştur. Sonuç olarak, bu çalışma C. cornucopioides'in yüksek antioksidanbileşenleri nedeniyle hücresel oksidatif stresi azaltabildiğini, patojenmikroorganizmalarının büyümesini inhibe edebileceğini ve en azından HepG2hücrelerine bir miktar hücre büyümesi inhibitör potansiyeline sahip olduğunugöstermektedir.

Gerçekleştirilen bu çalışmada farklı LED ışık kaynakları altında gerçekleştirilen hidropriming uygulamalarının Aspir bitkisinin (Carthamus tinctorius L.) tohum çimlenme, büyüme ve gelişmesi üzerine etkileri araştırılmıştır. Ayrıca hidropriming ve farklı ışık kaynaklarının etkileri biyokimyasal olarak incelenmiştir. Aspir tohumlarında oksidan/antioksidan biyobelirteçler (fenolikler, flavonoidler, β-karoten, likopen, toplam antioksidan kapasite (TAK), toplam oksidan kapasite (TOK), indirgeme gücü, DPPH radikal yakalama aktivitesi ve antioksidan enzim aktiviteleri) incelenerek tohumlarda meydana gelen biyokimyasal değişimler ortaya çıkarılmış ve fizyolojik değişimlerle ilişkilendirilmiştir. Çalışma sonuçları, ekim öncesi hidropriming uygulama süresi artıkça Aspirin köklenme ve gelişiminin belirli oranlarda baskılandığını göstermiştir. Karanlık ortamda ve farklı ışık kaynakları altında gerçekleştirilen hidropriming uygulamalarının genel olarak tohum antioksidan madde içeriğini (flavonoid, β-karoten, likopen, TAK, DPPH radikal yakalama aktivitesi, indirgeme gücü) yükselttiği, tohum oksidan kapasitesinde de kısmi bir artışa neden olduğu belirlenmiştir. TOK düzeyinde belirlenen artış, toplam fenolik madde içeriğindeki azalmayla açıklanmıştır. Ayrıca, ana antioksidan enzimlerinin Aspir tohum biyokimyasal içeriklerinin değişimiyle adaptif cevapla düzenlendikleri ortaya çıkarılmıştır. Bulgular, farklı ışık kaynakları altında gerçekleştirilen hidropriming uygulamalarının Aspir tohum antioksidan kapasitesini arttırarak tarımsal verimliliği arttırmada kullanılabilecek yöntemlerin araştırıldığı diğer çalışmalara öncül olabilecek niteliktedir. Effects of hydropriming applications under different LED lights on seed germination, growth and development of safflower plants (Carthamus tinctorius L.) were investigated in this study. Moreover, biochemical effects of hydropriming and light sources were also studied. Oxidant and antioxidant biomarkers (phenolics, flavonoids, β-carotene, lycopene, total antioxidant species (TAS), total oxidant species (TOS), reducing power, DPPH radical scavenging activity and antioxidant enzyme activities) were evaluated in safflower in order to reveal the interrelations between physiological and biochemical alterations. The results demonstrated that increasing the time of hydropriming suppreses the root growth and development of safflower plants upto some extent. In general, hydropriming applicaions in dark and under different light sources were found to amplify the seeds' antioxidant components (flavonoids, β-carotene, lycopene, TAS, DPPH scavenging activity and reducing power) together with an partial increase in seeds total oxidants. The rise in total oxidant status could be associated with a decline in total phenolic compounds. Furthermore, the main antioxidant enzymes were found to be regulated with an adaptive response to biochemical alterations in safflower seeds. The results of this study will direct the further studies concerning agricultural yields of safflower plants, since antioxidant capacity were found to be augmented in response to hydropriming applications carried out under different light sources. 71

WOS:000359821400003 PubMed:25238689 The increased consumption of high-fructose corn syrup (HFCS) may contribute to the worldwide epidemic of fatty liver. In this study, we have investigated whether HFCS intake (20 % beverages) influences lipid synthesis and accumulation in conjunction with insulin receptor substrate-1/2 (IRS-1; IRS-2), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1) and inducible NOS (iNOS) expressions in liver of rats. Resveratrol was tested for its potential efficacy on changes induced by HFCS. Animals were randomly divided into four groups as control, resveratrol, HFCS and resveratrol plus HFCS (resveratrol + HFCS). HFCS was given as 20 % solutions in drinking water. Feeding of all rats was maintained by a standard diet that enriched with or without resveratrol for 12 weeks. Dietary HFCS increased triglyceride content and caused mild microvesicular steatosis in association with up-regulation of fatty acid synthase and sterol regulatory element binding protein (SREBP)-1c in liver of rats. Moreover, HFCS feeding impaired hepatic expression levels of IRS-1, eNOS and SIRT1 mRNA/proteins, but did not change iNOS level. Resveratrol promoted IRS, eNOS and SIRT1, whereas suppressed SREBP-1c expression in rats fed with HFCS. Resveratrol supplementation considerably restored hepatic changes induced by HFCS. The improvement of hepatic insulin signaling and activation of SIRT1 by resveratrol may be associated with decreased triglyceride content and expression levels of the lipogenic genes of the liver. Gazi University Research FundGazi University [BAP 02/2011-39, 02/2012-48] This study was supported by grants from Gazi University Research Fund (BAP 02/2011-39 and 02/2012-48).

Bu çalışmada, Lepista nuda, Lycoperdon molle, Craterellus cornucopioides, Leucoagaricus leucothites, Laccaria laccata ve Armillaria mellea'nın in vitro sitotoksik, antioksidan ve antimikrobiyal aktiviteleri araştırılmıştır. Mantarların biyoaktif içerikleri (toplam fenolik, toplam flavonoid, β-karoten ve likopen içeriği), DPPH serbest radikal yakalama ve indirgeme gücü aktiviteleri test edilmiştir. En yüksek toplam fenolik asit miktarı her iki ekstrede de L. molle (Su; 57,12 µg/mg, metanol; 59,52 µg/mg) olarak belirlenmiştir. En yüksek β-karoten içeriğini su ekstresinde L. molle (3,990±0,091 µg/mg) ve metanol ekstresinde L. nuda (7,697±0,164 µg/mg) göstermiştir. En yüksek likopen içeriği ise su ekstresinde C. cornucopioides (2,492±0,009 µg/mg), metanol ekstresin de L. nuda'da (6,643±0,135 µg/mg) belirlenmiştir. Flavonoid miktarının en fazla olduğu tür metanol ekstresinde C. cornucopioides (1,83 µg/mg), su ekstresinde ise L. molle (4,061 µg/mg)'dir. DPPH yakalama aktivitelerine göre en yüksek etkiyi L. molle'nın metanol ekstresi göstermiştir. Antimikrobiyal test sonuçlarına göre en fazla etki L. nuda'nın su ekstresinde, HepG2 hücre canlılığı üzerine en yüksek etkiyi ise L. laccata türünün su ekstresi göstermiştir. Sonuç olarak çalışılan türlerin tamamının belirli oranlarda antioksidan özelliğe sahip olduğu, L nuda'nın su ekstresinin bütün mikroorganizmalar üzerinde olmamakla beraber en yüksek antimikrobiyal etkiyi gösterdiği ortaya çıkarılmıştır. HPLC ile gerçekleştirilen analizlerde mantar türlerinin hepsinde en yüksek oranda bulunan fenolik asitlerin p-kumarik asit ve gallik asit oldukları, L. molle metanol ve su ekstresinde p-kumarik asit, L. leucothites ekstrelerinde ise gallik asit yüksek oranda tespit edilmiştir. Sonuç olarak bu çalışmada incelenen mantar türlerinin insan vücudunda çeşitli metabolik faaliyetler sonucu meydana gelen hücre hasarını azaltabilecekleri ve zararlı mikroorganizmaları inhibe edebilecekleri belirli oranlarda HepG2 ve MCF-7 gibi hücrelere karşı sitotoksik etkiye sahip oldukları belirlenmiştir Antioxidant, antibacterial and in vitro cytotoxic protperties of Lepista nuda, Lycoperdon molle, Craterellus cornucopioides, Leucoagaricus leucothites, Laccaria laccata and Armillaria mellea was evaluated in this study. Bioactive ingredients of macrofungi (total phenolics, total flavonoids, β-carotene and lycopene), DPPH radical scavenging activities and reducing powers were determined. L. molle (water; 57,12 µg/mg, methanol; 59,52 µg/mg) were determined to have highest phenolic contents. Highest β-caroten contents were present in the aqueous extracts of L. molle (3,990±0,091 µg/mg) and methanolic extracts of L. nuda (7,697±0,164 µg/mg). Water extracts of C. cornucopioides (2,492±0,009 µg/mg) and methanolic extratcs of L. nuda (6,643±0,135 µg/mg) contains the top levels of lycopene contents among the others.Water extracts of C. cornucopioides (1,83 µg/mg) and methanolic extracts of L. molle (4,061 µg/mg) contains the largest amount of flavonoid as compared to other macrofungi. L. molle methanol extracts revealed the highest DPPH radical scavenging activities. Water extracts of L. nuda was the most effective agaist microorganisms and L. laccata was the most cytotocic macrofungi against HepG2 cell growth. As a result, all the studied macrofungi has some degree of antioxidant potential and antibacterial activities of L. nuda was superior over the other species. HPLC analysis revealed that p-coumaric acid and gallic acid were the most predominatig phenolics in studied macrofungi and both aqueous and methanolic extracts of L. molle contains very high p-coumeric acid levels. Besides, high amount of gallic acid were determined in both extracts of L. leucothites. In summary, this study revealed that aforementioned macrofungi species would reduce the cellular damages as a result of free radicals, inhibit the growth of pathogen microrganisms and have some degree of cell growth inhibitory potential at least to the certain cell lines such as HepG2 and MCF-7. 115

The effects of high-fructose diet on adipose tissue insulin signaling and inflammatory process have been poorly documented. In this study, we examined the influences of long-term fructose intake and resveratrol supplementation on the expression of genes involved in insulin signaling and the levels of inflammatory cytokines and sex hormones in the white adipose tissues of male and female rats. Consumption of high-fructose diet for 24 weeks increased the expression of genes involved in insulin signaling includingIR,IRS-1,IRS-2,Akt,PI3K,eNOS,mTOR, andPPARγ, despite induction of proinflammatory markers, iNOS, TNFα, IL-1β, IL-18, MDA, and ALT, as well as anti-inflammatory factors, IL-10 and Nrf2 in adipose tissues from males and females. Total and free testosterone concentrations of adipose tissues were impaired in males but increased in females, although there were no changes in their blood levels. Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well asiNOS,Nrf2, andPI3KmRNA, in adipose tissues of both genders. Dietary fructose activates both insulin signaling and inflammatory pathway in the adipose tissues of male and female rats proposing no correlation between the tissue insulin signaling and inflammation. Resveratrol has partly modulatory effects on fructose-induced changes.

İnsülin hormonunun yokluğu veya yetersizliği sonucu oluşan, karbonhidrat, yağ ve protein metabolizmasını etkileyen diyabet, pek çok dokuda harabiyet meydana getirmektedir. Kuvvetli bir antioksidan ve anti-inflamatuar molekül olan resveratrol, çeşitli hastalıkların önlenmesinde veya tedavisinde kullanım potansiyeline sahip bir bileşiktir. Bu çalışma, diyabetin böbrek dokularında meydana getirdiği oksidatif stres ve inflamasyon durumunun ortaya çıkarılması ve bu değişimlerin, antioksidan enzimleri (cat, sod, gpx ve gst) ve insülin sinyal iletimini (insülin Rβ, irs-1, pi3k, akt, mtor) nasıl etkilediklerini ortaya çıkarmaya yönelik gerçekleştirilmiştir. Ayrıca resveratrolün bu parametreler üzerine etkileri araştırılmıştır. Çalışmada erkek eşit yaşta Wistar sıçanları; diyabetik (n=12), kontrol (n=12), resveratrol verilmiş diyabetik (n=9), resveratrol verilmiş kontrol (n=12) olmak üzere dört gruba ayrıldıktan sonra iki grupta diyabet, streptozotocin'in (55 mg/kg) intraperitoneal yoldan enjekte edilmesiyle oluşturulmuştur. Diyabet oluşumunun bir hafta ardından 20 mg/kg resveratrol, ilgili gruplara günlük tek doz olarak 3 hafta boyunca enjekte edilmiştir. Diyabetin böbrek dokularında meydana getirdiği oksidatif stres ve inflamasyon durumu; lipid peroksidasyonu son ürünü MDA ve IL-6, IL-8, TNF-α gibi proinflamatuar sitokinlerin anlamlı (p

WOS:000379980500006 PubMed:26079852 Context: Oxidative stress has been implicated in the progression of pathogenesis in diabetes mellitus and leads to a variety of deformations in the central nervous system. Recent studies have provided several insights on therapeutic uses of resveratrol in diabetic complications.Objective: The present study determines if resveratrol ameliorates oxidative stress and molecular changes in the brain frontal cortex of streptozotocin-induced diabetic rats.Materials and methods: Rats were divided into four groups: control, diabetic, resveratrol-treated control, and resveratrol-treated diabetic. After diabetes induction, resveratrol (20mg/kg) was given intraperitoneally once daily for 4 weeks. In addition to enzymatic activities, gene and protein expression of brain antioxidant enzymes were utilized by qRT-PCR and Western blot, respectively.Results: The results indicated a significant elevation in total oxidant species (1.22-fold) and malonedialdehyde (1.38-fold) contents in diabetic rat brain cortex tissues. In addition, significant augmentation in the activities of catalase (1.38-fold) and superoxide dismutase (3-fold) was witnessed with the gene and protein expression levels reflecting a transcriptional regulation. Resveratrol treatment significantly normalized diabetic malonedialdehyde and oxidized glutathione levels and strengthens the action of all antioxidant enzymes. Recovery of the diabetes-associated changes reflects the reduction of oxidative conditions by resveratrol and reveals the decrease in the requirement for the activation of antioxidant defense systems in the brain tissues of diabetic rats.Discussion and conclusion: Potent antioxidant and neuroprotective properties of resveratrol against diabetes-induced oxidative damage were demonstrated and the results support the conduct of new studies searching for the molecular mechanism of diabetes-induced changes in brain tissues. TUBITAK Research FundTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T159]; Karamanoglu Mehmetbey UniversityKaramanoglu Mehmetbey University [BAP-08-YL-13] The authors report that they have no conflicts of interest. This study was supported by grants from TUBITAK Research Fund (112T159) and Karamanoglu Mehmetbey University (BAP-08-YL-13).

WOS:000356600100002 PubMed: 26109775 Background: Mushrooms have been valued for their nutritive content and as traditional medicines; several important medicinal properties of mushrooms have been recognized worldwide. Objective: The purpose of this study was to elucidate the cell growth inhibitory potential of four edible mushrooms; Coprinus comatus (O.F. Mull.) Pers. (Agaricaceae), Tricholoma fracticum (Britzelm.) Kreisel (Tricholomataceae), Rhizopogon luteolus Fr. and Nordholm (Rhizopogonaceae), Lentinus tigrinus (Bull.) Fr. (Polyporaceae) on hepatocellular carcinoma (HepG2) cells in conjunction with their antioxidant and antibacterial capacities. Materials and Methods: Five different extracts of edible mushrooms were obtained using water, methanol, acetone, n-hexane and chloroform as solvent systems for cytotoxic, antioxidant and antibacterial properties. Results: C. comatus showed substantial in vitro cytotoxic activity against HepG2 cell lines with all extracts especially with chloroform 50% inhibition (IC50 value of 0.086 mg/ml) and acetone (IC50 value of 0.420 mg/ml). Chloroform extract of C. comatus had maximum amount of beta-carotene (25.94 mu g/mg), total phenolic content (76.32 mu g/mg) and lycopene (12.00 mu g/mg), and n-hexane extract of L. tigrinus had maximum amount of flavonoid (3.67 mu g/mg). While chloroform extract of C. comatus showed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) capturing activity (1.579 mg/ml), the best result for metal chelating activity was obtained from methanolic extract (0.842 mg/ml). Moreover, all tested mushrooms demonstrated antibacterial activity and n-hexane extract of L. tigrinus and acetone extracts of T. fracticum were the most active against tested microorganism. Conclusion: These results indicate that different extracts of investigated mushroom have considerable cytotoxic, antioxidant and antibacterial properties and may be utilized as a promising source of therapeutics. Karamanoglu Mehmetbey University Scientific Research FundKaramanoglu Mehmetbey University [37-M-12] The authors are grateful to Karamanoglu Mehmetbey University Scientific Research Fund for financial support (37-M-12), Conflict of Interest: None declared.

S.absconditiflora Türkiye de yetişen ve bitki çayı olarak da tüketilen endemik Salvia türlerinden bir tanesidir. Yaprakları üzerindeki yüksek miktardaki damarlardan dolayı S.absconditiflora çok aktif bileşiklere sahiptir.S.absconditiflora'nın su ve metanol ekstrelerinin antioksidan kapasitelerine DPPH ve ABTS metodu ile bakıldı. Toplam fenolik ve flavanoid içerikleri spektroskopik teknik ile belirlendi. HPLC ve LC-MS/MS analizleri ile S.absconditiflora'nın içerisindeki bazı fenolik bileşiklerin varlığı 10 farklı standart kullanılarak belirlendi. Haziran su ekstresi en yüksek radikal yakalama kapasitesi gösterdi. Toplam flavanoid içeriği toplam fenolik içeriğinin 1/3'ü olarak belirlendi. Nisan metanol ekstresinin 108.77 mg GAE/g ekstre ile en yüksek toplam fenolik içeriğe sahip olduğu bulundu. S.absconditiflora 'nın ve 2 ana aktif bileşeninin sitotoksik etkileri HepG2 hücre hattı üzerinde XTT kolorimetrik ve tripan mavisi boyası ile incelendi. IC50 değeri 48 ve 72 saat uygulamaları ile tripan mavisi sayımı ile belirlendi.CYP enzimleri arasında, ilaç metabolizmasında rol alan en önemli beş enzim, CYP3A4, CYP2D6, CYP2C9, CYP2C19, ve CYP1A2 olarak bilinir ve bu enzimlerin gen ifadelerine bakıldığında Salvia su ekstresinin bu enzimlerin gen ifadelerinin hepsini arttırdığı görüldü. Sadece CYP1A2, CYP2D6 ve CYP2E1 gen ifadelerinin metanol ekstresi ile uyarıldığı, bununla birlikte, CYP2C9, CYP2C19 ve CYP3A4 gen ifadelerinin, metanol ekstresi uygulandığında inhibe edildiği bulundu. CYP3A4 enzimi tüm CYP enzim reaksiyonları içinde en önemli enzimdir. S.absconditiflora metanol ekstresinin CYP3A4 üzerindeki bu inhibe edici özelliği, karaciğerde, olası bitki-ilaç etkileşimine neden olabilir ve birlikte kullanılan ilacın biyoyarılanımını arttırarak toksik etkiye sebep olabilir. S.absconditiflora metanol ekstresinin inhibe edici etkisinin, içerisinde bol miktarda bulunan flavonoidler tarafından sağlanabileceği düşünülmektedir.GST Mu enzimlerinin hepsinin (M1-M5) gen ifadelerinin metanol ekstresi ile 3 ile 18 kat düştüğü görüldü. GSTM1 ve GSTM2 gen ifadeleri su ekstresi ile 1.5 kat düşerken, GSTM3 ve GSTM4 gen ifadelerinin su ekstresi ile 1.5 kat arttığı görüldü. Su ve metanol ekstrelerinin her ikiside de GST P1 gen ifadesini düştüğü gözlemlendi.Bu çalışmada kullanılan panel sonuçlarına göre, CYP enzimleri üzerine en güçlü etkiye S.absconditiflora metanol ekstresinin sahip olduğu bulundu. Diğer yandan, su ekstrelerinin CYP aktiviteleri üzerinde daha az etkisi olduğu görüldü.Çoğu kişi, S.absconditiflora yapraklarını çiğ ya da haşlanmış olarak tüketmektedir. Bu çalışmanın bulgularına bakıldığında su ekstrelerinin bitki-ilaç etkileşimleri dikkate alındığında güvenli olabileceğini düşünülmektedir S.absconditiflora is one of the endemic Salvia species grown in Turkey, which is consumed as a herbal tea. Because of the presence of high amounts of vesicles on their leaves, it is very rich in bioactive compounds. S.absconditiflora water and methanol extracts were studied for their antioxidant capacity by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ABTS free radical scavenging assay. Total phenolic and total flavonoid contents were quantified by spectrophotometric methods, HPLC and LC-MS/MS analyses and the results revealed the presence of several compounds and their quantities were calculated by using 10 different standards. June water extracts showed the highest % Radical Scavenging Activity against DPPH radical. Total flavonoid content was found as one third of the total phenolic content. April methanol extracts had the highest TPC (180.77 mgGAE/ g of dried extract) and June methanol extracts had highest TFC (21.8 mg QE/ g of dried extract).Cytotoxic effects of S.absconditiflora extracts and two standards, as main phenolic components, were examined in human hepatocyte carcinoma cell line, HepG2, via XTT colorimetric and Trypan Dye Exclusion cell viability assays. IC50 values in HepG2 cell line, after 48 and 72 hour incubations were determined. Effects of S.absconditiflora water and methanol extracts on the gene expressions of several Phase I and II enzymes were further investigated. Among CYP450 enzymes, only five accounts for major drug metabolism, namely CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP1A2 and water extracts induce the gene expression of all these CYP enzymes. Only CYP1A2, CYP2D6 and CYP2E1 gene expressions were induced with methanol extract. However, CYP2C9, CYP2C19 and CYP3A4 gene expressions were found to be inhibited with methanol extracts. CYP3A4 is the most important enzyme as its involved in almost all CYP450 mediated reactions. This inhibitory potential of S.absconditiflora methanol extract toward CYP3A4 could have potential herb-drug interaction in liver and might increase the bioavailability of co-adminestered drug and lead to toxicity. Inhibitory effect of methanol extract but not the water extract suggested that flavonoids, which exist abundantly in the methanol extract of S.absconditiflora may be responsible for this inhibition.Gene expression of all GST Mu enzyme (M1-M5) was inhibited by 3-18 fold with methanol extracts whereas water extracts inhibited M1 and M2 by 1.5 fold and induce M3 and M4 by again 1.5 fold. Both water and methanol extracts decreased the gene expression of GSTP1. According to our panel results we conclude that, the methanol extract of S.absconditiflora shows the most potent effects on CYP enzymes. On the other hand, the aqueous, water extract shows negligible effects on CYP activities. Since most individuals consume the leaves of S.absconditiflora either raw or boiled with water, the findings of this study suggest that the water extract may be safe considering the herb-drug interactions 168

WOS:000353332000097 PubMed: 25905778 This study was conducted to elucidate the genome-wide gene expression profile in streptozotocin induced diabetic rat liver tissues in response to resveratrol treatment and to establish differentially expressed transcription regulation networks with microarray technology. In addition to measure the expression levels of several antioxidant and detoxification genes, real-time quantitative polymerase chain reaction (qRT-PCR) was also used to verify the microarray results. Moreover, gene and protein expressions as well as enzymatic activities of main antioxidant enzymes; superoxide dismutase (SOD-1 and SOD-2) and glutathione Stransferase (GST-Mu) were analyzed. Diabetes altered 273 genes significantly and 90 of which were categorized functionally which suggested that genes in cellular catalytic activities, oxidation-reduction reactions, co-enzyme binding and terpenoid biosynthesis were dominated by up-regulated expression in diabetes. Whereas; genes responsible from cellular carbohydrate metabolism, regulation of transcription, cell signal transduction, calcium independent cell-to-cell adhesion and lipid catabolism were down-regulated. Resveratrol increased the expression of 186 and decreased the expression of 494 genes in control groups. While cellular and extracellular components, positive regulation of biological processes, biological response to stress and biotic stimulants, and immune response genes were up-regulated, genes responsible from proteins present in nucleus and nucleolus were mainly down-regulated. The enzyme assays showed a significant decrease in diabetic SOD-1 and GST-Mu activities. The qRT-PCR and Western-blot results demonstrated that decrease in activity is regulated at gene expression level as both mRNA and protein expressions were also suppressed. Resveratrol treatment normalized the GST activities towards the control values reflecting a post-translational effect. As a conclusion, global gene expression in the liver tissues is affected by streptozotocin induced diabetes in several specific pathways. The present data suggest the presence of several processes which contribute and possibly interact to impair liver functions in type 1 diabetes, several of which are potentially amenable to therapeutic interventions with resveratrol. Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T159] Funding was provided by Scientific and Technological Research Council of Turkey (TUBITAK-http://www.tubitak.gov.tr/en) with grant number of 112T159. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Bu çalışmada, Gaziantep yöresinde yetişen on makromantar türünün (Schizophyllum commune Fr., Lentinus tigrinus (Bull.) Fr., Coprinus comatus (O.F. Müll.) Pers., Rhizopogon luteolus Fr. & Nordholm, Volvopluteus gloiocephalus (DC.) Vizzini, Contu & Justo, Lactarius deliciosus (L.) Gray, Bovista plumbea Pers., Tricholoma terreum (Schaeff.) P. Kumm., Ramaria flava (Schaeff.) Quél. ve Agrocybe molesta (Lasch) Singer) antioksidan ve antimikrobiyal aktiviteleri araştırılmıştır. Mantarların biyoaktif içerikleri (toplam fenolik, toplam flavonoid, β karoten ve likopen içeriği), DPPH serbest radikal yakalama, metal şelatlama ve indirgeme gücü aktiviteleri test edilmiştir. En yüksek β-karoten (10,7 μg/mg), likopen (8,1 μg/mg) ve flavonoid (3,9 μg/mg ) değeri Bovista plumbea'nın su ekstresinde, en yüksek toplam fenolik içerik 27.52 μg/mg değerinde yine aynı türün metanol ekstresinde belirlenmiştir. EC50 değerlerine göre en yüksek DPPH yakalama aktivitesini (1,903 mg/mL) Ramaria flava'nın metanol ekstresi göstermiştir. DPPH yakalama aktivitelerine göre en yüksek etkiyi her iki ekstrede de Ramaria flava türü göstermiştir. Yüzdelik metal şelatlama aktivitelerine göre en yüksek etkiyi su ekstresinde Coprinus comatus, metanol ekstresinde ise Tricholoma terreum göstermiştir. Test edilen mantar türlerinin su ekstresinde Bovista plumbea'nın, metanol ekstrelerinde ise Ramaria flava'nın diğer türlere kıyasla yüksek seviyede indirgeme gücü aktivitesi gösterdiği belirlenmiştir. Antimikrobiyal test sonuçlarına göre en fazla etki Ramaria flava'nın metanol ekstresinde gözlenirken, her iki ekstrede de Rhizopogon luteolus hiç etki göstermemiştir. Sonuç olarak çalışılan türlerin tamamının belirli oranlarda antioksidan özellik taşıdığı, S. commune, L.tigrinus, C. comatus, V. gloiocephalus, L. deliciosus, B. plumbea, T. terreum, R. flava ve A. molesta türlerinin ise antimikrobiyal etkiye sahip olduğu ortaya çıkarılmıştır. Bu çalışma ile incelenen, mantar türlerinin insan vücudunda çeşitli metabolik faaliyetler sonucu meydana gelen hücre hasarını azaltabilecekleri ve zararlı mikroorganizmaları inhibe edebilecekleri belirlenmiştir.Anahtar Kelimeler: Makromantarlar, Antioksidan Etki, Antimikrobiyal Etki In this study, the antioxidant and antimicrobial activities of ten macrofungi species (Schizophyllum commune Fr., Lentinus tigrinus (Bull.) Fr., Coprinus comatus (O.F. Müll.) Pers., Rhizopogon luteolus Fr. & Nordholm, Volvopluteus gloiocephalus (DC.) Vizzini, Contu & Justo, Lactarius deliciosus (L.) Gray, Bovista plumbea Pers., Tricholoma terreum (Schaeff.) P. Kumm., Ramaria flava (Schaeff.) Quél. and Agrocybe molesta (Lasch) Singer) growing in Gaziantep province were investigated. Bioactive content of macrofungi (total phenolic content, total flavonoid content, β carotene and lycopene content), DPPH free radical scavenging, metal chelating and reducing power activities were tested. The highest β-carotene (10,7 µg/mg), lycopene (8,1 µg/mg) and flavonoid (3,9 µg/mg) contents were found in water extracts of Bovista plumbea and the highest total phenolic content of 27,52 µg/mg value was also determined for its methanol extracts. According to EC50 values, the highest DPPH radical scavenging activity (1.903 mg/mL) was shown by the methanol extract of Ramaria flava. In terms of DPPH radical scavenging activities, the highest activity was presented by Ramaria flava for both extracts. Metal chelating activity of water extract of Coprinus comatus has the highest effect but Tricholoma terreum had the highest effect for methanol extract. Among the tested fungal species, aqueus extracts of Bovista plumbea has the highest reducing power, while the methanol extracts of Ramaria flava had the highest reducting power, compared to other species. According to antimicrobial test results, maximum effect was observed in the methanol extract of Ramaria flava, while no effect was observed for both extract of Rhizopogon luteolus. As a result, all of the studied taxa were found to have have antioxidant properties, and S. commune, L. tigrinus, C. comatus, V. gloiocephalus, L. deliciosus, B. plumbea, T. terreum, R. flava and A. molesta were found to have antimicrobial activity. With this study, it is presented that the studies species may reduce cell damage occuring as a result of various metabolic activities, and may inhibit harmful microorganisms. 71

Diyabetin beyin fonksiyonları üzerine hayati etkilerinin olduğu ve çeşitli beyin bölgelerini etkileyerek öğrenme ve hafıza fonksiyonlarında bozukluklar ortaya çıkardığı son yıllarda yapılan çalışmalarla gösterilmiştir. Bu çalışma; beyin antioksidan enzimlerinin diyabet ile nasıl değişim gösterdiğini ve resveratrolün diyabetin neden olduğu değişimleri düzenleyici etkilerini ortaya çıkarmak için gerçekleştirilmiştır. Erkek Wistar sıçanlarında diyabet; streptozotocin'nin (55mg/kg) intraperitonial yoldan enjekte edilmesiyle oluşturulmuştur. Bir hafta ardından, resveratrol günlük 20mg/kg olmak üzere yirmi dört gün boyunca verilmiş ve beyin dokularında antioksidan enzimlerin gen ve protein ekspresyon düzeyleri ile aktivitelerinin ölçümleri moleküler ve biyokimyasal teknikler kullanılarak belirlenmiştir.Sonuçlar beyin dokularında CAT, GPx, SOD-1 ve GST (Mu ve Pi) enzimlerinin gen ekspresyon düzeylerinin diyabet ile anlamlı bir şekilde yükseldiğini göstermiştir. Western blot ve aktivite ölçümlerine göre gen ifadesindeki bu artışlar, aynı zamanda çoğu enzimin protein ve aktivite düzeyinde de artış meydana getirmiştir. mRNA, protein ve aktivitedeki bu artış, diyabetik beyin dokularında antioksidan enzimlerin genellikle transkripsiyon düzeyinde düzenlendiğini göstermektedir. Resveratrol; GPx, SOD-1 ve GST (Mu ve Pi) enzimlerinde diyabet ile meydana gelen gen ifadesi değişimlerini tekrar kontrol düzeylerine yaklaştırmıştır. İfade düzeyleri artan bu genlerin resveratrol ile tekrar kontrol düzeylerine yaklaşması; diyabetin neden olduğu oksidatif stresin, beyin dokularında resveratrol ile azaltıldığını ve dolayısı ile enzim aktivasyonu için gen ifade düzeyini yükseltmeye gerek kalmadığını göstermektedir. Sonuç olarak bu çalışma ile resveratrol gibi kuvvetli bir antioksidan molekülün diyabetin neden olduğu olası değişimleri iyileştirici veya düzenleyici etkileri ortaya çıkarılmış ve diyabetin neden olduğu moleküler değişiklikleri inceleyen diğer çalışmalara yön verebilecek sonuçlar elde edilmiştir.Anahtar Kelimeler: Diyabet, Resveratrol, Antioksidan Enzimler, Gen Ekspresyonu Recently, it has been shown that diabetes has detrimental effects on brain functions. It has negative outcomes on learning capabilities and memory functions by affecting different regions of brain. This study was designed to demonstrate how diabetes changes the antioxidant enzyme status in brain tissues and how resveratrol mediates these diabetes induced alterations. Diabetes was induced in male Wistar rats by streptozotocin (55kg/mg) injection to intraperitonial cavity. After one week, resveratrol were administered as 20mg/kg daily injections throughout twenty four days. Then, gene and protein expression levels and activity status of the antioxidant enzymes were measured from brain tissues with molecular and biochemical techniques.According to results; gene expression levels of CAT, GPx, SOD-1 and GST (Mu and Pi) enzymes were found to be up-regulated in diabetic brain tissues. Western blot results and activity measurements showed that most of these enzymes' protein and activity levels were also augmented reflecting that antioxidant enzymes were regulated in diabetic brain tissues at the level of transcription. Application of resveratrol to diabetic animals restored the enhanced antioxidant enzyme status towards the control values. Restoration of these genes to the control levels indicates that diabetes induced oxidative stress were lowered with resveratrol application. Therefore, there was no need for the induction of brain antioxidant enzymes with resveratrol in diabetes.As a result, in this study it has been revealed that a strong antioxidant molecule such as resveratrol may restore or modulate the changes induced by diabetes in brain tissues. By this way, the results have been put forward to orient the new studies searching for molecular mechanism of diabetes induced changes in brain tissues. Keywords: Diabetes, Resveratrol, Antioxidant Enzymes, Gene Expression 104