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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 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 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 Effects of lycopene on plasma glucose, insulin levels, oxidative stress, and body weights of streptozotocin-induced diabetic rats(Tubitak Scientific & Technological Research Council Turkey, 2012) Aydin, Muhsin; Celik, SefaAim: To determine possible therapeutic effects of oral lycopene supplementation on plasma insulin levels, lipid peroxidation, blood glucose levels, and the antioxidant defense system of streptozotocin-induced diabetic rats. Materials and methods: Classical biochemical methods were used to determine plasma malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) levels. Enzyme-linked immunosorbent assay was used to determine plasma insulin levels and reverse transcriptase-polymerase chain reaction was used to determine the levels of brain antioxidant enzymes (SOD, CAT, and GSH-Px). Results: It was found that the diabetes-related increase in blood glucose levels was reduced by supplementation of lycopene over an 8-week period. Plasma NO levels and brain tissue GSH levels were meaningfully reduced in the treatment group compared to the diabetic group. In the hemolysate samples, it was determined that the treatment group's SOD, CAT, and GSH-Px activities significantly increased compared to the diabetic group. In the brain tissue homogenates, CAT and SOD activity did not show a significant change, whereas GSH-Px activity was increased in the treatment group compared to the diabetic group. SOD, CAT, and GSH-Px mRNA transcription levels were suppressed in the diabetic group compared to the control, and this suppression was stopped and increases were significantly induced by the supplementation of lycopene. Conclusion: In this study, the oxidative damage and low insulin levels associated with diabetes were ameliorated with the administration of lycopene. The results of this study indicate that lycopene is an effective nutritional component to alleviate and/or prevent the complications of diabetes, and these findings can be used as a basis for future studies.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 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.
