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Öğe Acute oxidant and inflammatory effects of imidacloprid on the mammalian central nervous system and liver in rats(Academic Press Inc Elsevier Science, 2010) Duzguner, Vesile; Erdogan, SuatImidacloprid is a neonicotinoid insecticide and has been extensively used as a crop pest and pet flea control programme because it's high specificity as an insecticide Imidacloprid toxicity on mammalian tissues has not been adequately evaluated In the present study, potential acute neuro and liver toxic effects of imidacloprid were analyzed in rats as a model of mammalian using antioxidant-oxidant and inflammatory system 10 mu M imidacloprid was administrated intravenously and 2 h post-administration, the rats were sacrificed, liver and brains were surgically removed Exposure to imidacloprid led to significant increases in nitric oxide concentrations in brain, liver and plasma samples The quantitative mRNA transcriptional analyses demonstrated that imidacloprid-elevated production of NO levels due to the induction of NOS in liver, but neither nNOS nor iNOS were induced in brain The oxidant-generating enzymes xanthine oxidase and myeloperoxidase activities in both tissues were elevated and significant lipid peroxidation in liver and plasma was observed The antioxidant catalase, superoxide dismutase and glutathione peroxidase activities were differently responded to imidacloprid administration Significant intracellular glutathione depletion was also measured in both tissues Imidacloprid treatment up-regulated inflammatory cytokmes TNF-alpha, IL-6 and IL-1 beta mRNA transcriptions by 2 5- to 5 2-fold increases in both brain and liver Conversely, anti-inflammatory mediator IL-10 mRNA was down-regulated in both organs These results suggest that imidacloprid cause oxidative stress and inflammation in central nervous system and liver in non-target organisms in rats (C) 2009 Elsevier Inc All rights reservedÖğe Assessing the effects of the neonicotinoid insecticide imidacloprid in the cholinergic synapses of the stellate cells of the mouse cochlear nucleus using whole-cell patch-clamp recording(Elsevier Science Bv, 2010) Bal, Ramazan; Erdogan, Suat; Theophilidis, George; Baydas, Giyasettin; Naziroglu, MustafaImidacloprid (IMI) is widely used systemic insecticide that acts as an agonist on nicotinic acetylcholine receptors (nAChRs). IMI has been reported to be more active against insect nAChRs (EC(50) 0.86-1 mu M) than it is against mammalian nAChRs (EC(50) 70 mu M). The objective of this study was to determine to what extent IMI affects the nAChRs of the stellate cells of mouse cochlear nucleus (CN), using whole-cell patch-clamp recording. Puff application of 1 mu M IMI had no significant effect on the membrane properties of the neurons tested, while a concentration of 10 mu M caused a significant depolarizing shift in the membrane potential and resulted in increases in the fluctuation of the membrane potential and in the frequency of miniature postsynaptic potentials (mpps) within less than a minute of exposure. IMI at concentrations >= 50 mu M caused a significant depolarizing shift in the membrane potential, accompanied by a marked increase in the frequency of action potential. IMI decreased the membrane input resistance and the membrane time constants. Bath application of 50 mu M d-tubocurarine (d-TC) reversibly blocked the depolarizing shift of the resting membrane potential and the spontaneous firing induced by IMI application in Current clamp and blocked the inward Currents through nicotinic receptors induced by IMI application in voltage clamp. Similarly, 100 nM alpha-bungarotoxin (alpha-BgTx) blocked the spontaneous firing induced by IMI (n = 3). The amplitude of the 100 mu M IMI-induced inward current at -60 mV holding potential was 115.0 +/- 16.2 pA (n = 7). IMI at a concentration of 10 mu M produced 11.3 +/- 3.4 pA inward current (n = 4). We conclude that exposure to IMI at concentrations >= 10 mu M for <1 min can change the membrane properties of neurons that have nAChRs and. as a consequence, their function. (C) 2009 Elsevier Inc. All rights reserved.Öğe Beneficial effects of nontoxic ozone on H2O2-induced stress and inflammation(Canadian Science Publishing, 2016) Kucukgul, Altug; Erdogan, Suat; Gonenci, Ramazan; Ozan, GoncaIn this study, the anti-oxidant and anti-inflammatory efficacy of ozone oxidative preconditioning (OOP) were investigated on hydrogen peroxide (H2O2)-induced human lung alveolar cells. In MTT and trypan blue viability tests, while 100 mu mol/L H2O2 caused a 17.3% and 21.9% decrease in the number of living cells, respectively, ozone at 20 mu mol/L regenerated cell proliferation and prevented 9.6% and 11.0% of cell loss, respectively. In addition, H2O2 decreased the transcription levels of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) 5.43-, 2.89-, and 5.33-fold, respectively, while it increased Bax, NF-kappa beta, TNF-alpha, and iNOS expression 1.57-, 1.32-, 1.40-, and 1.41-fold, respectively. Ozone pretreatment, however, increased CAT, GPx, and SOD transcription levels 7.08-, 5.17-, and 6.49-fold and decreased Bax, NF-kappa beta, TNF-alpha, and iNOS transcriptions by 1.25-, 0.76-, 3.63-, and 7.91-fold, respectively. Moreover, intracellular glutathione (GSH) level and SOD activity were decreased by 46.2% and 45.0% in the H2O2 treatment group, and OOP recovered 58.5% and 20.1% of the decreases caused by H2O2. H2O2 also increased nitrite levels 7.84-fold, and OOP reduced this increase by half. Consequently, OOP demonstrated potent anti-oxidant and anti-inflammatory effects on in vitro model of oxidative stress-induced lung injury.Öğe Caffeic acid phenethyl ester (CAPE) exhibits significant potential as an antidiabetic and liver-protective agent in streptozotocin-induced diabetic rats(Academic Press Ltd- Elsevier Science Ltd, 2009) Celik, Sefa; Erdogan, Suat; Tuzcu, MehmetCaffeic acid phenethyl ester (CAPE) was screened for hypoglycemic and liver-protective activity in streptozotocin (STZ)-induced diabetic rats. Diabetes was established by single dose STZ injection (45 mg kg(-1) bw, i.p.) for 48h.CAPE wasinjected atdoses of 10, 20 and 30 mu Mkg(-1) bw day(-1) (i.p.) to the rats in CAPEI, CAPEII and CAPEIII groups 2 days after induction of diabetes and continued for 60 days, thereafter. It was found that diabetes down-regulated the expressions of glucokinase (7.8-fold) and pyruvate kinase (6.4-fold) in comparison to control, however, phoshoenolpyruvate carboxykinase mRNA levels were up-regulated by 2.2-fold. CAPE treatments enhanced the expressions of glucokinase (3.4-14.9-folds), and pyruvate kinase (3.2-12.8-folds) mRNAs in diabetic rats. However, phoshoenolpyruvate carboxykinase mRNA expression was decreased by CAPE to varying degrees (1.2-5.5-fold). CAPE increased (similar to 2-fold) the level of plasma insulin previously decreased by STZ treatment. Here we demonstrate that CAPE significantly decreased the fasting blood levels of glucose, alanine aminotransferase, cholesterol, and triglyceride induced by diabetes. CAPE increased the liver glycogen level lowered by diabetes. In histopathological evaluation of the liver, CAPE treatments were seen to reduce necrosis and anisonucleosis in hepatocytes, and connective tissue elevated in the portal region by diabetes. CAPE exhibits a significant potential as an antidiabetic agent by suppressing hepatic glucose output via inducing mRNA expression of glucokinase and pyruvate kinase, whilst inhibiting phoshoenolpyruvate carboxykinase in diabetes. CAPE also has the ability to decrease the harmful effects of diabetes on the liver of rats. (C) 2009 Elsevier Ltd. All rights reserved.Öğe Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats(Springer, 2008) Celik, Sefa; Erdogan, SuatDiabetic patients reveal significant disorders, such as nephropathy, cardiomyopathy, and neuropathy. As oxidative stress and inflammation seem to be implicated in the pathogenesis of diabetic brain, we aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on oxidative stress and inflammation in diabetic rat brain. Diabetes was induced by a single dose of streptozotocin (45 mg kg(-1), i.p.) injection into rats. Two days after streptozotocin treatment 10 mu M kg(-1) day(-1) CAPE was administrated and continued for 60 days. Here, we demonstrate that CAPE significantly decreased the levels of nitric oxide and malondialdehyde induced by diabetes, and the activities of catalase, glutathione peroxidase, and xanthine oxidase in the brain. However, glutathione levels were increased by CAPE. The mRNA expressions of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, and inducible nitric oxide synthase (iNOS) were remarkably enhanced in brain by diabetes. CAPE treatments significantly suppressed these inflammatory cytokines (about 70% for TNF-alpha, 26% for IFN-gamma) and NOS (completely). Anti-inflammatory cytokine IL-10 mRNA expression was not affected by either diabetes or CAPE treatments. In conclusion, diabetes induces oxidative stress and inflammation in the brain, and these may be contributory mechanisms involved in this disorder. CAPE treatment may reverse the diabetic-induced oxidative stress in rat brains. Moreover, CAPE reduces the mRNA expressions of TNF-alpha and IFN-gamma in diabetic brain; suggesting CAPE suppresses inflammation as well as oxidative stress occurred in the brain of diabetic patients.Öğe Caffeic acid phenethyl ester suppresses oxidative stress in Escherichia coli-induced pyelonephritis in rats(Springer, 2007) Celik, Sefa; Gorur, Sadik; Aslantas, Ozkan; Erdogan, Suat; Ocak, Sabahattin; Hakverdi, SibelAlthough oxidative damage is known to be involved in inflammatory-mediated tissue destruction, modulation of oxygen free radical production represents a new approach to the treatment of inflammatory diseases. Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, has antioxidant, anti-inflammatory and antibacterial properties. For that reason, we aimed to investigate the efficiency of CAPE administration in preventing oxidative damage in pyelonephritis (PYN) caused by Escherichia coli. In this study, 35 Wistar rats were grouped as follows: control, PYN 24 h, PYN 48 h, PYN 72 h, CAPE 24 h, CAPE 48 h and CAPE 72 h. E. coli (1 x 10(9) c.f.u.) were inoculated into the rats in both PYN and CAPE groups via urethral catheterization. Ten mu M/kg-body weight CAPE was injected to the rats in all CAPE groups 24 h before E. coli infection, and injections were repeated at 24-h intervals. Rats were sacrificed 24 h, 48 h and 72 h after infection in both PYN and CAPE groups. Malondialdehyde (MDA) and nitric oxide (NO) levels were significantly increased in kidneys of PYN groups. The activities of the antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XO) were also elevated by E. coli. However, CAPE administration reduced MDA and NO levels, as well as XO activity, although it increased SOD and GSH-Px activities. Histopathological examination showed that CAPE reduced the inflammation grade induced by E. coli. In conclusion, CAPE administrations decrease the oxidative damage occurring in PYN and therefore could be used for medical management of bacterial nephropathy.Öğe Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene(Portland Press Ltd, 1997) Bolger, Graeme B.; Erdogan, Suat; Jones, Randy E.; Loughney, Kate; Scotland, Grant; Hoffmann, Ralf; Wilkinson, IanWe have isolated and characterized complete cDNAs for two isoforms (HSPDE4D4 and HSPDE4A5) encoded by the human PDE4D gene, one of four genes that encode cAMP-specific rolipram-inhibited 3',5'-cyclic nucleotide phosphodiesterases (type IV PDEs; PDE4 family). The HSPDE4D4 and HSPDE4D5 cDNAs encode proteins of 810 and 746 amino acids respectively. A comparison of the nucleotide sequences of these two cDNAs with those encoding the three other human PDE4D proteins (HSPDE4D1, HSPDE4D2 and HSPDE4D3) demonstrates that each corresponding mRNA transcript has a unique region of sequence at or near its 5'-end, consistent with alternative mRNA splicing. Transient expression of the five cDNAs in monkey COS-7 cells produced proteins of apparent molecular mass under denaturing conditions of 68, 68, 95, 119 and 105 kDa for isoforms HSPDE4D1-5 respectively. Immunoblotting of human cell lines and rat brain demonstrated the presence of species that co-migrated with the proteins produced in COS-7 cells. COS-cell-expressed and native HSPDE4D1 and HSPDE4D2 were found to exist only in the cytosol, whereas HSPDE4D3, HSPDE4D4 and HSPDE4D5 were found in both cytosolic and particulate fractions. The IC50 values for the selective PDE4 inhibitor rolipram for the cytosolic forms of the five enzymes were similar (0.05-0.14 ?M), whereas they were 2-7-fold higher for the particulate forms of HSPDE4D3 and HSPDE4D5 (0.32 and 0.59 ?M respectively), than for the corresponding cytosolic forms. Our data indicate that the N-terminal regions of the HSPDE4D3, HSPDE4D4 and HSPDE4D5 proteins, which are derived from alternatively spliced regions of their mRNAs, are important in determining their subcellular localization, activity and differential sensitivity to inhibitors.Öğe Chronic exposure to imidacloprid induces inflammation and oxidative stress in the liver & central nervous system of rats(Academic Press Inc Elsevier Science, 2012) Duzguner, Vesile; Erdogan, SuatImidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor (nAChR) in insects, and potentially in mammals. In the present study, oxidant and inflammatory responses to chronic exposure of imidacloprid was studied in rats. Wistar rats were randomly allocated into two groups as control and imidacloprid-exposed group (n = 10 rat/each group). 1 mg/kg/BW/day imidacloprid was administrated orally by gavage for 30 days. After exposure, rats were euthanized and liver and brain samples were surgically removed for analyses. Imidacloprid application caused a significant increase in nitric oxide production in brain (p < 0.05) and liver (p < 0.001). The quantitative analyses of mRNA confirmed the finding that imidacloprid induced the mRNA transcriptions of the three isoforms of nitric oxide synthases (iNOS, eNOS, nNOS) in brain and two isoforms (iNOS, eNOS) in the liver. Exposure to imidacloprid caused significant lipid peroxidation in plasma, brain (p < 0.001) and liver (p < 0.003). While the superoxide-generating enzyme xanthine oxidase activity was elevated in both tissues (p < 0.001), myeloperoxidase activity was increased only in the liver (p < 0.001). Antioxidant enzyme activities showed various alterations following exposure, but a significantly depleted antioxidant glutathione level was detected in brain (p < 0.008). Evidence of chronic inflammation by imidacloprid was observed as induction of pro-inflammatory cytokines such as TNF-alpha, IL-1 beta, IL-6, IL-12 and IFN-gamma in the liver and brain. In conclusion, chronic imidacloprid exposure causes oxidative stress and inflammation by altering antioxidant systems and inducing pro-inflammatory cytokine production in the liver and central nervous system of non-target organisms. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.Öğe Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production(Elsevier Sci Ltd, 2010) Erdogan, Suat; Tosyali, Eda; Duzguner, Vesile; Kucukgul, Altug; Aslantas, Ozkan; Celik, SefaBrucella species are able to survive and replicate within the phagocytic cells and cause chronic infections in domestic animals and humans. Modulation of programmed cell death by Brucella spp. may be one of the reasons of the chronicity of the infection. In this study, whether cisplatin treatment, an apoptotic anticancer agent, would enhance the host resistance against Brucella melitensis-infected human macrophage-like cells was investigated. The infection neither induced inflammation nor oxidative stress. But, Brucella caused a decrease in infected macrophage viability of 36% at 48 h postinfection (p.i.) as compared with uninfected cells. Treatment of infected macrophages with 20 mu M cisplatin for 48 h caused a large increase in nitric oxide (NO) levels in a time-dependent manner via induction of iNOS transcription. Cisplatin also enhanced glutathione peroxidase, myeloperoxidase and xanthine oxidase activities, providing evidence of generation of reactive free radicals. N-acetylcysteine was able to decrease cisplatin-induced NO, and prevented the agent-induced apoptosis, similar to effects found in L-NAME (N(G)-nitro-L-arginine methyl ester) treatment. Cisplatin stimulated inflammation through the induction of TNF-alpha and IL-12 secretion, and down-regulated Brucella-stimulated IL-10 transcription. The number of infected cells and their viability were decreased by 80% at 48 h p.i. by cisplatin in comparison with infected cells. Similar to this result, cisplatin treatment resulted in reduced intracellular CFU of B. melitensis being reduced by 80% at 48 h p.i. These findings demonstrate that pharmacological agents such as cisplatin may be considered to influence immune responses and apoptosis to help decrease Brucella-infected cell number. (C) 2009 Elsevier Ltd. All rights reserved.Öğe Effect of lycopene administration on plasma glucose, oxidative stress and body weight in streptozotocin diabetic rats(Taylor & Francis Ltd, 2008) Duzguner, Vesile; Kucukgul, Altug; Erdogan, Suat; Colik, Sefa; Sahin, KazimTo evaluate the role of lycopene, a carotenoid antioxidant, on streptozotocin (STZ)-induced diabetic rats, 12 female rats received a single intraperitonial injection of STZ at a dose of 45 mg/kg body weight of which 6 were given 10 mg/kg lycopene orally (test group) once daily for 21 days. The administration of STZ caused a significant increase in plasma glucose and decrease in body weight. The supplementation of lycopene significantly reduced diabetic plasma glucose level by 25% and prevented body weight loss starting from 14(th) day of lycopene administration. Although tissue lipid peroxidation and nitric oxide (NO) levels were unchanged, lycopene administration significantly reduced diabetes-elevated lipid peroxidation and NO in plasma. It was concluded that lycopene supplementation may be valuable for correcting hyperglycemia and preventing diabetic complications caused by lipid peroxidation and free radicals.Öğe The effects of increased cAMP content on inflammation, oxidative stress and PDE4 transcripts during Brucella melitensis infection(Elsevier Sci Ltd, 2008) Erdogan, Suat; Aslantas, Ozkan; Celik, Sefa; Atik, EsinCyclic AMP (cAMP) is a key intracellular second messenger which at increased levels has been shown to have anti-inflammatory and tissue-protective effects. Its concentration is determined by the activities of both adenylate cyclase (AC) and the phosphodiesterase (PDE) enzymes. The aim of this study was to compare the effects of increased cAMP and glucocorticoid dexamethasone administration on B. melitensis-induced lipid peroxidation, Brucella suppressed antioxidant enzyme activities and PDE4 transcripts in rats. Intracellular cyclic AMP level was elevated by two different approaches; activation of AC and inhibition of PDE activities. Rats were inoculated with B. melitensis for seven days then a single dose of nonselective PDE inhibitor 3-isobutyl-1-methylxanthine.(IBMX), the adenylate cyclase activator forskolin and dexamethasone were administrated to each infected group, and animals were challenged for 48 h. Brucella-induced lipid peroxidation was significantly reduced by the cAMP elevating agents as well as dexamethasone administration in plasma, liver and spleen. The antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased by the pathogen. Whilst suppressed GSH-Px activity was reversed by cAMP elevating agents, SOD activity was not restored. Superoxide generating enzyme xanthine oxidase activity was not altered at the end of the infection period. Brucella infection increased plasma IL-12 level and this effect was also suppressed by the cAMP elevating agents, whereas TNF-alpha, IFN-gamma and IL-10 levels were unchanged. Intracellular cAMP levels are entirely hydrolyzed by cAMP-specific PDE 4 isozymes (PDE4s) in inflammatory and immunocompetent cells. Brucella reduced mRNA transcript levels for PDE4A by 40%, though PDE4B and 4D transcriptions were being unaffected in spleen. It was concluded that B. melitensis infection decreased activity of the antioxidant defence system, induced lipid peroxidation and suppressed PDE4A transcription. Administration of cAMP elevating agents exhibited similar affect with dexamethasone on lipid peroxidation, IL-12 production and antioxidant enzyme activities in Brucella infection. (C) 2007 Elsevier Ltd. All rights reserved.Öğe Evaluation of oxidative stress and inflammation in long term Brucella melitensis infection(Springer, 2006) Melek, Ismet M.; Erdogan, Suat; Celik, Sefa; Aslantas, Ozkan; Duman, TaskinThe Brucella genus is able to cause chronic infection in a wide range of mammals including humans. Oxidative events, lipid peroxidation and inflammatory response against Brucella infection have not yet been well elucidated in vivo. We have investigated oxidative/antioxidative status and nitric oxide production in plasma, brain, liver and spleen during a 60 day period of B. melitensis infection in a rat model. In addition, inducible nitric oxide synthase (iNOS), IL-10, IL-12, IFN-gamma and TNF-alpha mRNA transcriptions were analyzed by semiquantitative reverse transcriptase PCR (RT-PCR) in brain samples. Animals were infected with B. melitensis and sacrificed at 7th, 15th, 30th, 45th and 60th day of post-inoculation. Malondialdehyde (MDA), as an indicator of lipid peroxidation, and nitric oxide (NO) concentrations were significantly increased after Brucella inoculation and began to decline to basal levels from 45th day in plasma, liver and spleen. However, iNOS transcription was not induced during the infection period in brains. In contrast, MDA level was increased in brain during the late phase of infection without any change in NO production. The infection did not alter the antioxidant enzyme activities in the tissues; although significantly increased catalase activity was observed between days 30 and 45 in the liver. Transcription analyses demonstrated that IL-10, IL-12 and IFN-gamma mRNA level were not induced in the brain. Only TNF-alpha mRNA was weakly up-regulated in brain 30 days after pathogen inoculation. The results obtained in this study demonstrate that B. melitensis induces lipid peroxidation and NO production in the liver and spleen in the early days of infection, but that these levels subsequently decline. Moreover, Brucella does not appear to induce antioxidant enzyme activities and inflammation during two months of infection. However, the pathogen does stimulate cerebral lipid peroxidation in the late phase of infection without causing significant inflammation.Öğe Expression, intracellular distribution and basis for lack of catalytic activity of the PDE4A7 isoform encoded by the human PDE4A cAMP-specific phosphodiesterase gene(2004) Johnston, Lee Ann; Erdogan, Suat; Cheung, York Fong; Sullivan, Michael; Barber, Rachael; Lynch, Martin J.; Baillie, George S.PDE4A7 is an isoform encoded by the human PDE4A cAMP-specific phosphodiesterase gene that fails to hydrolyse cAMP and whose transcripts are widely expressed. Removal of either the N-or C-terminal unique portions of PDE4A7 did not reconstitute catalytic activity, snowing that they did not exert a chronic inhibitory effect. A chimera (Hyb2), formed by swapping the unique N-terminal portion of PDE4A7 with that of the active PDE4A4C form, was not catalytically active. However, one formed (Hyb1) by swapping the unique C-terminal portion of PDE4A7 with that common to all active PDE4 isoforms was catalytically active. Compared with the active PDE4A4B isoform, Hyb1 exhibited a similar Km value for cAMP and IC50 value for rolipram inhibition, but was less sensitive to inhibition by Ro-20-1724 and denbufylline, and considerably more sensitive to thermal denaturation. The unique C-terminal region of PDE4A7 was unable to support an active catalytic unit, whereas its unique N-terrninal region can. The N-terminal portion of the PDE4 catalytic unit is essential for catalytic activity and can be supplied by either highly conserved sequence found in active PDE4 isoforms from all four PDE4 subfamilies or the unique N-terminal portion of PDE4A7. A discrete portion of the conserved C-terminal region in active PDE4A isoforms underpins their aberrant migration on SDS/PAGE. Unlike active PDE4A isoforms, PDE4A7 is exclusively localized to the P1 particulate fraction in cells. A region located within the C-terminal portion of active PDE4 isoforms prevents such exclusive targeting. Three functional regions in PDE4A isoforms are identified, which influence catalytic activity, subcellular targeting and conformational status.Öğe Inhibition of cigarette smoke induced-inflammation and oxidative damage by caffeic acid phenethyl ester in A549 Cells(BRNSS Publication Hub, 2016) Kucukgul, Altug; Erdogan, SuatIntroduction: The main objective of this study was to evaluate the effect of antioxidative and antiapoptotic effects and underlying molecular mechanisms of caffeic acid phenethyl ester (CAPE) on human lung epithelial cells exposed to cigarette smoke (CS). Materials and Methods: Human alveolar epithelial A549 cells were exposed to CS and treated with various concentrations of CAPE for 24 h, and their effective concentrations were identified by cell viability assay (MTT). Antioxidant and anti-inflammatory effect of CAPE on nuclear erythroid related factor-2 (Nrf2) and nuclear factor-?? (NF-??) protein levels were analyzed by Western blotting. Furthermore, caspase 8 gene expression level was analyzed by reverse transcription-quantitative polymerase chain reaction. Results: Low concentration CAPE pretreatment rescued 52% of CS-exposed A549 cells from death. CS upregulated gene expression level of caspase 8 by 4.28 fold. However, 2.5 ?M CAPE pretreatment increased caspase 8 level by 52%. CS exposure also elevated NF-?? (p65) protein level by 70%, however, CAPE pretreatment significantly reversed this activation. While CS exposure decreased Nrf2 protein levels by 48% as compared with the control group, CAPE pretreatment increased Nrf2 protein level two folds approximately according to CS group. Discussion: CAPE markedly decreased inflammatory transcription factor NF-kB and increased antioxidant response element Nrf2 protein expression levels in CS-exposed human alveolar cells. According to the data obtained from this study, CAPE could be used as a strategic alternative to support treatment of inflammatory and oxidative stress-induced lung diseases.Öğe Inhibition of Cigarette Smoke Induced-inflammation and Oxidative Damage by Caffeic Acid Phenethyl Ester in A549 Cells(Asian Journal Pharmaceutics, 2016) Kucukgul, Altug; Erdogan, SuatIntroduction: The main objective of this study was to evaluate the effect of antioxidative and antiapoptotic effects and underlying molecular mechanisms of caffeic acid phenethyl ester (CAPE) on human lung epithelial cells exposed to cigarette smoke (CS). Materials and Methods: Human alveolar epithelial A549 cells were exposed to CS and treated with various concentrations of CAPE for 24 h, and their effective concentrations were identified by cell viability assay (MTT). Antioxidant and anti-inflammatory effect of CAPE on nuclear erythroid related factor-2 (Nrf2) and nuclear factor-kappa beta (NF-kappa beta) protein levels were analyzed by Western blotting. Furthermore, caspase 8 gene expression level was analyzed by reverse transcription-quantitative polymerase chain reaction. Results: Low concentration CAPE pretreatment rescued 52% of CS-exposed A549 cells from death. CS upregulated gene expression level of caspase 8 by 4.28 fold. However, 2.5 mu M CAPE pretreatment increased caspase 8 level by 52%. CS exposure also elevated NF-kappa beta (p65) protein level by 70%, however, CAPE pretreatment significantly reversed this activation. While CS exposure decreased Nrf2 protein levels by 48% as compared with the control group, CAPE pretreatment increased Nrf2 protein level two folds approximately according to CS group. Discussion: CAPE markedly decreased inflammatory transcription factor NF-kB and increased antioxidant response element Nrf2 protein expression levels in CS-exposed human alveolar cells. According to the data obtained from this study, CAPE could be used as a strategic alternative to support treatment of inflammatory and oxidative stress-induced lung diseases.Öğe Low concentration of oleic acid exacerbates LPS-induced cell death and inflammation in human alveolar epithelial cells(Taylor & Francis Inc, 2017) Kucukgul, Altug; Erdogan, SuatPurpose: The current study aimed to investigate in vitro effects of oleic acid on lipopolysaccharide (LPS)-induced acute lung injury in the human lung epithelial cells (A549). Materials and Methods: The cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests. Selected gene expression levels were analyzed by Real-Time Quantitative-Polymerase Chain Reaction (RT-qPCR). Results: 24hours of LPS (100ng/mL) exposure decreased the cells' viability by 44.6% compared to untreated control. Low concentration (2.5nM) of oleic acid slightly suppressed the cell survival by 9.1% analyzed 24hours after incubation. However, oleic acid pretreatment before LPS exposure significantly increased cell survival loss to 63.9%. LPS exposure decreased the expressions of catalase (CAT) and glutathione peroxidase (GPx) mRNA levels by 2.8 and 2.5 fold, respectively. Moreover, pretreatment of the cells with oleic acid strengthened LPS-decreased expressions of CAT and GPx genes by 3.5 and 6.7 fold, respectively. The mRNA expressions of superoxide dismutase (SOD), induced nitric oxide synthase (iNOS), interleukin-1 beta, IL-12, COX-2, caspase-3 and caspase-8 were increased by 2.4, 2.2, 2.2, 2.3, 3.0, 2.6, and 2.5 fold, respectively, by LPS, and oleic acid pretreatment significantly potentiated the effect of LPS. Conclusion: Oleic acid worsens LPS-induced cell death by potentiating oxidative stress and inflammation in A549 lung epithelial cells.Öğe The Neuroprotective Effect of Caffeic Acid Phenethyl Ester on Global Ischemia-Reperfusion Injury in Rat Brains(Kafkas Univ, Veteriner Fakultesi Dergisi, 2014) Altug, Muhammed Enes; Melek, Ismet M.; Erdogan, Suat; Duzguner, Vesile; Ozturk, Atakan; Kucukgul, AltugThe aim of this study was to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE) on phosphodiesterase 4 (PDE4) mRNA isoenzymes, oxidant and antioxidant defence in ischemia/reperfusion (I/R) injured rat brains. Twenty-one rats were randomly divided into three equal groups: sham-control, ischemia/reperfusion (I/R) and I/R+CAPE. Rats in sham-control group underwent only surgical intervention without bilateral common carotid artery occlusion. Ischemia/reperfusion was induced by bilateral common carotid artery occlusion with atraumatic clips for 30 min, followed by artery reopening. The I/R+CAPE group was subjected to the same surgical procedure as I/R group, but CAPE was administered intraperitoneally at the dose of 15 mu mol kg(-1) twice, 1 h before occlusion and at 12th h of reperfusion. The rats were sacrificed 24 h after I/R. The cAMP concentration was analyzed by ELISA and PDE4 isozyme mRNA transcriptions were evaluated by qRT-PCR methodology in the brain cortex. Ischemia-induced NO production was significantly attenuated by CAPE in the cerebral cortex. CAPE significantly enhanced GSH-Px activity, while SOD, CAT and XO activities non-significantly changed, as compared to the I/R group. CAPE significantly decreased PDE4A and PDE4B transcripts, without changing cAMP levels compared to I/R group. Ischemia-induced neurologic deficit scores were reduced by CAPE. These results suggest that CAPE slightly modulates the antioxidant defense system and NO release in rat brain during global cerebral ischemia/reperfusion injury. In addition, CAPE treatments produce the neuroprotective effect by reducing the levels of some PDE4 transcriptions.Öğe Oral administration of lycopene reverses cadmium-suppressed body weight loss and lipid peroxidation in rats(Springernature, 2007) Rencuzogullari, Nadir; Erdogan, SuatCadmium (Cd) exposure has been recognized to result in a wide variety of cellular responses, including oxidative stress and body weight loss. The aim of the present study was to examine the effect of lycopene supplementation on the antioxidant defense system, lipid peroxidation (LPO) level, nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) production, and body weight in Cd-exposed rats. Animals were divided into four groups (n = 7): control, Cd-treated, Cd plus lycopene-treated, and lycopene-treated. Cadmium (as CdCl2) was administrated orally for 20 days (6.6 mg kg(-1) day(-1)), and lycopene (10 mg kg-1 day(-1)) was similarly administered. Lycopene administration significantly suppressed Cd-induced LPO in plasma and kidney homogenates. Lycopene also reversed Cd-decreased body weight compared to the control. Cadmium treatment had diverse effects on the antioxidant enzyme activities. Although antioxidant superoxide dismutase activity was unchanged, glutathione peroxidase activity was decreased, and catalase activity was elevated in kidney homogenates of Cd-administrated group. However, lycopene treatment reversed Cd-changed enzyme activities to the control level. Xanthine oxidase activity and TNF-alpha concentration were not altered by Cd administration, indicating that superoxide anion production and inflammation were not stimulated. Cadmium did not change NO levels in kidney homogenates but decreased those in plasma, and this effect was not prevented by lycopene supplementation. The result suggests that consumption of adequate levels of lycopene may be useful to prevent heavy-metal-induced LPO and body weight loss.Öğe Preventive effect of rolipram, a phosphodiesterase 4 enzyme inhibitor, on oxidative renal injury in acute ascending pyelonephritis model in rats(Elsevier Science Inc, 2008) Goeruer, Sadik; Celik, Sefa; Hakverdi, Sibel; Aslanta, Oezkan; Erdogan, Suat; Aydin, Muhsin; Ocak, SabahattinOBJECTIVES To evaluate the effects of rolipram, a phosphodiesterase 4 enzyme inhibitor, on Escherichia coli-induced renal oxidative damage in an acute pyelonephritis (PYN) rat model. METHODS A total of 35 male Wistar albino rats were randomly divided into 7 groups (n = 5) as follows: control (uninfected), PYN 24 hours, PYN 48 hours, PYN 72 hours, PYN + rolipram 24 hours, PYN + rolipram 48 hours, and PYN + rolipram 72 hours. Ascending PYN was induced in the study groups by E. coli inoculation into the bladder, and the urethras were then occluded by collodium for 4 hours. Rolipram injections (1 mg/kg) were started before bacterial inoculation and repeated at 24-hour intervals in the PYN + rolipram groups until death. The rats were killed at the indicated times. Malondialdehyde and nitric oxide levels and superoxide dismutase and catalase activities were determined in kidney homogenates. Histopathologic examinations were also performed. RESULTS Tissue malondialdehyde and nitric oxide levels and superoxide dismutase and catalase activities were significantly increased in the kidneys from the PYN groups. However, rolipram administration reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. The histopathologic examinations demonstrated that rolipram treatment reduced the inflammation grade in the kidney specimens. CONCLUSIONS The results of our study have shown that rolipram has a protective effect on renal tissue from E. coli-induced oxidative injury. Therefore, phosphodiesterase 4 inhibitors might be a novel therapeutic option for the prevention and/or management of acute PYN.Öğe Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity in rats(Wiley, 2007) Ocak, Sabahattin; Gorur, Sadik; Hakverdi, Sibel; Celik, Sefa; Erdogan, SuatThe objective of this study was to compare the beneficial effects of caffeic acid phenethyl ester (CAPE), vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity. Thirty rats were randomly devided into six groups: (i) control; (ii) vancomycin, 200 mg/kg administrated via intraperitoneal route; (iii) vancomycin plus CAPE - vancomycin with 10 mu mol/kg CAPE; (iv) vancomycin plus vitamin C - vancomycin (intraperitoneally) with 200 mg/dl vitamin C in drinking water; (iv) vancomycin plus vitamin E - vancomycin with 1000 mg/kg body weight vitamin E (intramuscularly); and (vi) vancomycin plus N-acetylcysteine - vancomycin with 10 mg/kg body weight (intraperitoneally) of N-acetylcysteine. Vancomycin treatments were started I day after the first administrations of these agents and continued for 7 days. At the end of the experiments, catalase activity was significantly decreased by vancomycin in kidney homogenates (P < 0.05). Vitamin E, vitamin C, N-acetylcysteine and CAPE administrations decreased the blood urea nitrogen levels increased by vancomycin, although significant differences were detected only in the vitamins E and C groups (P < 0.05). Increased renal malondialdehyde and nitric oxide levels by vancomycin were significantly suppressed by agents used in the study (P < 0.05). Histopathological examination demonstrated prominent damages in the vancomycin-treated group. Vitamin E was the most beneficial agent on vancomycin-induced tubular damage, followed by vitamin C, N-acetyleysteine and CAPE treatments, respectively. The data suggest that vitamin E, as well as vitamin C, N-acetyleysteine and CAPE, could be useful for reducing the detrimental effects on vancomycin-induced toxicity in kidneys.