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Öğe Chemical and biological characteristics of propolis from Apis mellifera caucasica from the Ardahan and Erzurum provinces of Turkey: a comparative study(Inst Medical Research & Occupational Health, 2021) Arslan, Mehmet; Sevgiler, Yusuf; Guven, Celal; Murathan, Zehra Tugba; Erbil, Nurcan; Yildirim, Deniz; Buyukleyla, MehmetThe aim of this study was to compare the biological activities of ethanolic propolis extracts of Apis mellifera caucasica obtained from Ardahan and Erzurum provinces of Turkey. Samples were tested for antioxidant, anticytotoxic, anticarcinogenic, antibacterial, and antifungal potentials using different techniques. Propolis samples from the two provinces had different mineral and organic compositions related to their geographical origin. The ferric reducing antioxidant power (FRAP) test showed superiority of Ardahan propolis over the Erzurum. Regardless of origin and the presence of mitomycin C in the culture medium, propolis enhanced human peripheral lymphocyte viability, which depended on the duration and propolis concentration. Antiperoxidative activity on MCF-7 breast cancer cells was concentration-dependent. Erzurum propolis showed the highest anticarcinogenic activity at the concentrations of 62.5 mu g/mL and 125 mu g/mL, which dropped at higher concentrations. All propolis samples also showed antibacterial activity against the tested human pathogens similar to ampicillin and penicillin controls, except for Pseudomonas aeruginosa. However, they did not exert any antifungal activity against Candida albicans and Yarrowia lipolytica. In conclusion, propolis samples from both provinces showed promising biological activities, but further research should focus on finding the right concentrations for optimal effect and include the cell necrosis pathway to get a better idea of the anticarcinogenic effects.Öğe Comparative developmental toxicity evaluation of di-n-hexyl phthalate and dicyclohexyl phthalate in rats(Sage Publications Inc, 2017) Ahbab, Muefide Aydogan; Guven, Celal; Kockaya, Evrim Arzu; Barlas, NurhayatTo investigate the effects of di-n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) on the development of fetus and placenta in utero, pregnant rats were exposed to DHP or DCHP at dosages of 0, 20, 100, and 500 mg/kg bw/day, by gavage, on gestational days 6-19. Anogenital distance (AGD) and AGD-body weight(1/3) ratio of female fetuses decreased in all treatment groups in a non-dose-response way. The ossification centers of bones and the intensity of Alizarin red stain of the fetuses decreased in all treatment groups. The white blood cell levels of fetuses in DHP and DCHP exposed groups increased at all dosages. Mean cell hemoglobin, hemoglobin concentrations, and hemoglobin levels of all DHP and DCHP treated male and female fetuses were reduced. Histopathologic changes (hemorrhage in labyrinth, degeneration of spongiotrophoblast, hemorrhage, decreased and irregular vessel formation, and edema in the basal zone) were observed in placentas at high dosages of DHP and DCHP. In contrast, there was no change in weight gain of dams in DHP and DCHP exposed groups compared to control, but resorption rate, reduced fetal weight, delayed ossification, placental disruption, and hematologic parameters clearly indicated that in utero DHP and DCHP exposure resulted in intrauterine growth retardation in rats.Öğe EFFECT OF ELAMIPRETIDE ON MITOCHONDRIAL FUNCTIONS IN MICE WITH OXALATE NEPHROPATHY(Springer, 2022) Dursun, Ismail; Guven, Eylem Taskin; Guven, Celal; Doganyigit, Zuleyha; Guvenilir, Ecma; Memis, Mehmet; Taheri, Serpil[Abstract Not Available]Öğe Effects of Different Ammonia Levels on Tribenuron Methyl Toxicity in Daphnia magna(Springer, 2021) Over, Sevgi Basalan; Guven, Celal; Taskin, Eylem; Cakmak, Arif; Benli, Petek Piner; Sevgiler, YusufThe present study investigates the toxicity of the herbicide tribenuron methyl (TBM) as an anthropogenic agent and ammonia as an abiotic factor on Daphnia magna at environmentally relevant concentrations. These stressors may coexist in surface waters in agricultural regions. To achieve this objective, D. magna were exposed to TBM at a nominal concentration of 0.81 mu g/L in association with a low ammonia (LA) concentration of 0.65 mg/L and a high ammonia (HA) concentration of 1.61 mg/L in acute toxicity tests of 96-h duration and chronic toxicity tests of 21-day duration. The D. magna also were exposed to TBM, HA, and LA singly. The D. magna were analysed for various biomarkers of sublethal toxicity. Glutathione peroxidase (GPx), glutathione S-transferase (GST), cholinesterase (ChE) enzyme activities, and levels of thiobarbituric acid reactive substances (TBARS) and total protein were determined spectrophotometrically. Mitochondrial membrane potential (MMP) was analysed by microscopy with fluorescence staining. Cytochrome c and 5 ' AMP-activated protein kinase (AMPK) were analysed by Western blotting. Morphometric properties were examined microscopically. This is the first study in which AMPK, an indicator of intracellular energy, was measured in D. magna. GST and ChE enzyme activities and TBARS and total protein levels did not change during acute exposures (i.e., 96 h) in all treatments. GPx activity increased in D. magna from the HA + TBM treatment compared with single-exposure groups. The level of cytochrome c protein was elevated in D. magna from the LA and LA + TBM treatments. AMPK protein levels increased in all treatments with daphnids, except in the LA group. MMP was depolarised in D. magna from all treatments, whereas the most notable change was observed in HA + TBM mixture group in chronic exposures. The results show that GST and ChE may not be sensitive biomarkers for evaluating the sublethal toxic effects to D. magna exposed to environmentally relevant concentrations of ammonia and TBM. Acute and chronic exposure to ammonia and TBM probably caused an energetic crisis in D. magna. Therefore, AMPK and MMP are promising biomarkers for these toxicants.Öğe Herbal medicine in diabetes mellitus with cardiovascular diseases(Springer International Publishing, 2019) Kaya, Salih Tunc; Guven, Celal; Taskin, Eylem[No abstract available]Öğe Living with female rats exposed to restraint stress during pregnancy caused depressive-like behavior in male rats and stress-induced apoptosis(Wiley, 2021) Kocahan, Sayad; Akillioglu, Kubra; Sencar, Leman; Sahin, Leyla; Cevik, Ozge Selin; Taskin, Eylem; Guven, CelalObjective Maternal mood disorders such as postpartum depression (PPD) can negatively affect the lives not only of mothers but also of partners. The purpose of this study investigates emotional behavior and hippocampal apoptosis alterations of the male live with a postpartum depressed female. Methods Pregnant rats in the stress group were exposed to restraint stress (RS). The male rats who shared the same cages were not exposed to RS. To explain the consequences of depressive-like behavior and anxiety, animals were exposed to the forced swim test (FST), open-field test (OFT), and elevated plus maze (EPM). The apoptotic cell number was detected by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP biotin nick-end labeling (TUNEL) staining. Results According to FST, PPD caused more immobility, reduced swimming, and climbing compared to control groups in the stressed female and male (p < 0.05). For the crossing number of squares in the center area, the main effect of the group was significant (p < 0.05). Stressed groups have a higher crossing number of squares in the center area compared to control groups. In the OFT, there was a significant increase in the time spent in the center area in the stress female and male group compared to the control female and male group (p < 0.05). For the EPM, time spent in the close arms was increased in the control male and stress male compared to the stress female group (p < 0.05). Female and male rats with PPD demonstrated apoptosis in neuron and glial cells in the hippocampus. Conclusions The present study demonstrates that RS results in PPD in females. Furthermore, it implicates RS as a potential risk factor for the development of postpartum mood disorder in males. Most of the studies on paternal PPD have been done by using self-report questionnaires. Studies on physiological and hormonal changes during the postpartum period among fathers would provide information on biological factors of depression.Öğe Mild regular treadmill exercise ameliorated the detrimental effects of acute sleep deprivation on spatial memory(Elsevier, 2021) Sahin, Leyla; Cevik, Ozge Selin; Cevik, Kenan; Guven, Celal; Taskin, Eylem; Kocahan, SayadVulnerable areas like the hippocampus are sensitive to insults such as sleep deprivation (SD); they are also susceptible to environmental enrichment. Much evidence is accumulating that chronic sleep deprivation causes alterations in the hippocampus that responsible for spatial memory. However, there is conflicting about the differences between acute and chronic SD results. The purpose of this study was to determine the protective effects of mild treadmill exercise on acute SD rats. Four groups were created as control, exercise, sleep deprivation, exercise + sleep deprivation. Multiple platforms method was used to induce REM sleep deprivation (RD) for 48 h. The exercise was applied five days per week for four weeks (5 x 4). For the first and second weeks, the length of the exercise was 15 min in two sessions (5 min interval) followed by 15 min in three, 15 min in four sessions. Morris water maze (MWM) was used as a spatial memory test. Gene level was determined by using the qPCR technique. Malondialdehyde (MDA) content in the hippocampus was measured as an extent of peroxidative damage to lipids by using the ELISA method. 48 h RD impaired long-term spatial memory significantly. Mild, regular treadmill exercise ameliorated the detrimental effects of acute sleep deprivation on memory. There was no significant difference in MDA between groups. Hippocampal gene expression did not show any changes in all groups. Lack of correlation between memory impairment and levels of genes in the hippocampus is likely to be related to the differences in behavioral and genetic mechanisms.Öğe Oxidative and apoptotic effects of fluoxetine and its metabolite norfluoxetine in Daphnia magna(Inst Medical Research & Occupational Health, 2020) Over, Sevgi Basalan; Guven, Celal; Taskin, Eylem; Sevgiler, YusufThe aim of this study was to investigate the oxidative and apoptotic potential of fluoxetine, a widely used antidepressant in Turkey and the world. and of its metabolite norfluoxetine on a model non-target organism, Daphnia magna to see how exposure to this group of antidepressants (specific serotonin reuptake inhibitors) could affect the aquatic environment in which they end up. Juvenile D. magna specimens were chronically exposed to fluoxetine and norfluoxetine alone and in combination at concentrations found in the aquatic environment (0.091 and 0.011 mu g/L, respectively) and to their 10-fold environmental concentrations for 21 days. Another group of 17-day-old animals were subacutely exposed to 100-fold environmental concentrations for four days. After exposure, we measured their glutathione peroxidase (GPx) and cholinesterase (ChE) activities, thiobarbituric acid-reactive substances (TBARS), and total protein content spectrophotometrically, while mitochondrial membrane potential (MMP) was analysed by fluorescence staining, and cytochrome c and ERK1/2 protein content by Western blotting. This is the first-time cytochrome c and ERK1/2 were determined at the protein level in D. magna. We also measured their carapace length, width. and caudal spine length microscopically. At environmental concentrations fluoxetine and norfluoxetine caused an increase in ChE activity and brood production. They also caused a decrease in juvenile carapace length, width, and caudal spine length and depolarised the mitochondrial membrane. At 10-fold environmental concentrations. GPx activity, lipid peroxidation levels. cytochrome c. and ERK1/2 protein levels rose. The most pronounced effect was observed in D. inagna exposed to norfluoxetine. Norfluoxetine also decreased brood production. Similar effects were observed with subacute exposure to 100-fold environmental concentrations. However, total protein content decreased. All this confirms that fluoxetine and norfluoxetine have oxidative and apoptotic potential in D. magna. Daphnia spp. have a great potential to give us precious insight into the mechanisms of environmental toxicants, but there is still a long way to go before they are clarified in these organisms.Öğe Silencing HMGB1 expression inhibits adriamycin's heart toxicity via TLR4 dependent manner through MAPK signal transduction(Imprimatur Publications, 2020) Taskin, Eylem; Guven, Celal; Kaya, Salih Tunc; Sariman, Melda; Emrence, Zeliha; Ekmekci, Sema Sirma; Abaci, NeslihanPurpose: Adriamycin (APR) is a commonly used anti-cancer drug. ADR has toxic effects on cardiomyocytes and leads to heart failure. However, the underlying mechanism(s) by which ADR causes heart failure is still not clarified exactly. The aim of present study is to investigate whether ADR-induced heart failure is mediated via HMGB1/TLR4 to initiate the apoptosis through MAPK/AMPK pathways. Methods: H9c2 cell line was used to create four groups as a control, HMGB1 inhibition, ADR, ADR+HMGB1 inhibition. Silencing HMGB1 was performed with specific small interfering RNA. ADR was used at 2 mu M concentration for 36 and 48 hours. Protein and genes expressions, apoptosis was measured. Results: Although ADR decreased AMPK, pAMPK, ERK1/2, pERK1/2, p38, JNK protein expression, ADR+HMGB1 inhibition led to change those protein expressions. The effect of silencing of HMGB1 prevented apoptosis induced by ADR in the cells. HMGB1 caused changes a kind of posttranscriptional modification on the TLR4 receptor. This posttranscriptional modification of TLR4 receptor led to decreased AMPK protein level, but phosphorylated-AMPK. This alternation of AMPK protein caused enhancing of JNK protein, resulting from the decline of p38 and ERK protein levels. Eventually, JNK triggered apoptosis by a caspase-dependent pathway. The number of TUNEL positive and active caspase 8 cells at ADR was high, although HMGB1 silencing could decrease the cell numbers. Conclusions: Inhibition of HMGB1 might prevent the lose of the cardiac cell by inhibition of apoptotic pathway, therefore HMGB1 plays an essential role as amplifying on ADR toxicity on the heart by TLR4.Öğe The Identification of Intracellular Signalling Pathway Through DHMGB1/TLR2 Axis on Myocardial Ischemia/Reperfusion Injury-Induced Apoptosis(Wiley, 2022) Guven, Eylem Taskin; Guven, Celal; Kaya, Salih Tunc; Keles, Ayse Ikinci; Destegul, Dilek; Pelit, Aykut; Gunay, Ismail[Abstract Not Available]Öğe The role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity(Pergamon-Elsevier Science Ltd, 2019) Taskin, Eylem; Guven, Celal; Kaya, Salih Tunc; Sahin, Leyla; Kocahan, Sayad; Degirmencioglu, Arife Zuhal; Gur, Fatih MehmetAims: Doxorubicin, an anticancer drug, has a toxic effect on many tissues such as heart, pancreas, liver, kidney, and testis. The aim of current study is to investigate whether melatonin would be protective in doxorubicin-induced beta (beta) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-kappa B signaling pathway. Main methods: Human pancreatic beta cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10 mu M), doxorubicin (2 mu M) and the combination of melatonin with doxorubicin. Following 24-h treatment, Mitogen-activated protein kinase (MAPKs), Toll like receptors (TLRs) including TLR2 and TLR4, pro-and anti-apoptotic protein expression levels were determined by western blotting. Total antioxidant (TAS), oxidant status (TOS) and oxidative stress index (OSI) of the cells as well as superoxide dismutase (SOD) levels were determined. Active caspase-8 activity was measured and TUNEL staining was performed to study apoptotic pathways. Mitochondrial membrane potential (MMP), some protein expressions and F-actin distribution were analyzed. Key findings: Doxorubicin caused to depolarize MMP, resulting in enhancing apoptosis by activation of caspase-8 via MAPKs/NF-kappa B pathway via elevation of TOS and decreasing TAS. Also, doxorubicin destroyed F-actin distribution and elevated TLR2 and some apoptotic proteins, including Bax. However, co-treatment of melatonin with doxorubicin could reverse depolarization of MMP and inhibition of apoptosis through MAPK/NF-kappa B signaling by decreasing TOS and increasing TAS. The co-treatment reversed the alternations of TLR2, TLR4, MAPKs and apoptotic protein expressions induced by doxorubicin. Significance: Melatonin could be a good candidate against pancreatic beta cell toxicity-induced by doxorubicin through TLR2/TLR4/MAPK/NF-kappa B pathways.Öğe Thymoquinone improves testicular damage and sperm quality in experimentally varicocele-induced adolescent rats(Wiley, 2021) Gur, Fatih Mehmet; Timurkaan, Sema; Taskin, Eylem; Guven, Celal; Gur, Hatice Emel; Senturk, Meryem; Dastan, SevgiThe aim of this study was to investigate the protective and therapeutic effects of thymoquinone against the negative effects of varicocele on testicular tissue and sperm morphology. Five groups were formed by random selection from a total of 40 adult male Wistar rats (n = 8). Thymoquinone (5 mg/kg/day) was administered intraperitoneally to the varicocele-dimethyl sulfoxide-olive oil-thymoquinone (VT) group and the sham-thymoquinone group. At the end of the 60th day, all groups were anaesthetised and the left testis was removed from the body quickly. One half of the testis tissue, which was divided into two, was separated for biochemical and Western blot analysis, while the other half were fixed in Bouin's fixative. As a result of biochemical, molecular and histopathological analyses, a statistically significant increase was found in the varicocele group testicular tissues in the malondialdehyde level, apoptotic index, Bax expression, cytochrome c expression and Bax/Bcl-2 ratio compared with the sham group. In addition, histopathological changes characterised by partial or complete degeneration of the germinal epithelium were observed in the seminiferous tubules in the same group. Total oxidant status level and sperm count with abnormal morphology increased in varicocele group, whereas total antioxidant status level decreased. In the VT group, all of the biochemical, molecular and histopathological changes detected in the varicocele group were statistically significantly reduced. When the findings obtained in this study are evaluated, it can be said that thymoquinone has the potential to be used as a preventive and therapeutic pharmacological agent in the medical treatment of varicocele. Although the exact mechanism of action of thymoquinone has not been fully elucidated, the findings obtained in this study support the view that thymoquinone showed a cytoprotective effect by reducing apoptosis, oxidative stress and lipid peroxidation.