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Öğe Autism: Evaluation of psychological, biochemical and environmental factors(2019) Kar, Fatih; Cihaner, Ömer; Hacıoğlu, Ceyhan; Kanbak, GüngörUnderstanding the abnormal biochemical and psychological mechanisms underlying autism spectrum disorders,identifying the impacts caused by environmental factors, and exciting studies for researchers and clinicians are importantbecause research on our understanding of the main causes of autism is expected to lead to new approaches to diagnosis,treatment and prognosis. This review will focus on the effects of recent studies on biochemical markers and environmentalfactors, including MRI studies in the brain, which focus on the causes and treatment of autism.Öğe Betaine suppresses cell proliferation by increasing oxidative stress-mediated apoptosis and inflammation in DU-145 human prostate cancer cell line(Springer, 2019) Kar, Fatih; Hacıoğlu, Ceyhan; Kaçar, Sedat; Şahintürk, Varol; Kanbak, GüngörProstate cancer is the main cause of cancer-related mortality in men around the world and an important health problem. DU-145 human prostate cancer cells provide an opportunity to investigate prostate cancer. Betaine has a number of anticancer effects, such as inactivation of carcinogens, inhibition of cancer cell proliferation, angiogenesis, and metastasis. However, there is no study investigating the effects of betaine on DU-145 cells. The aim of this study was to evaluate the effects of different concentrations of betaine on the oxidative stress, apoptosis, and inflammation on DU-145 cells. Firstly, we proved the cytotoxic activity of betaine (0 to 150 mg/ml) on DU-145 cells by using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and defined the optimal concentration of betaine. Then, by employing the doses found in MTT, the levels of antioxidant (GSH, SOD, CAT, and TAS) and oxidant (MDA and TOS) molecules, pro-inflammatory cytokines (TNF-a and IL-6), apoptotic proteins (CYCS and CASP3), and DNA fragmentation were measured. Morphological changes and apoptosis were evaluated using H&E technique, Bax and Bcl-2 immunohistochemistry. Results suggested that betaine caused oxidative stress, inflammation, inhibition of cell growth, apoptosis, and morphological alterations in DU-145 cells dose-dependently. Furthermore, treatments with increasing betaine concentrations decreased the antioxidant levels in cells. We actually revealed that betaine, known as an antioxidant, may prevent cell proliferation by acting as an oxidant in certain doses. In conclusion, betaine may act as a biological response modifier in prostate cancer treatment in a dose-dependent manner.Öğe Bexarotene inhibits cell proliferation by inducing oxidative stress, DNA damage and apoptosis via PPAR gamma/ NF-kappa B signaling pathway in C6 glioma cells(Humana Press Inc, 2021) Hacioglu, Ceyhan; Kar, Fatih; Kacar, Sedat; Sahinturk, Varol; Kanbak, GungorGliomas are one of the most aggressive brain tumors with a poor prognosis in the central nervous system. Bexarotene is a third-generation retinoid X receptor agonist that is promising in the treatment of both cancer and neurodegenerative diseases. In this study, we aimed to investigate the cytotoxic and anti-proliferative effects of bexarotene in C6 glioma cells through the PPAR gamma/NF-kappa B pathway. In the study, first cytotoxic bexarotene concentrations for C6 cells were detected, and then apoptosis profile, reactive oxygen species (ROS), total antioxidant (TAS), 8-hydroxy-2 '-deoxyguanosine (8-OHdG) and nuclear factor-kappa B (NF-kappa B) levels in the cells were determined. In addition, peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNA expression analysis was carried out. As a result, we detected concentration- and time-dependent antiproliferative effects of bexarotene on C6 cells. We found that bexarotene treatment decreased NF-kappa B and TAS levels and increased PPAR gamma and 8-OHdG levels in C6 cells. Bexarotene enhanced PPAR gamma expression in a dose-dependent manner when compared to the control group (P < 0.01). Furthermore, we determined that bexarotene-induced apoptotic C6 cells enhanced through Annexin V-FITC/PI staining and caspase-3/-7 activation analyses since phosphatidylserine level on the outer surface of the cell membrane and caspase-3/-7 activities were increased in the cells treated with bexarotene. In conclusion, bexarotene treatment in C6 glioma cells could modulate apoptosis profile, DNA damage, ROS production, and reduction of TAS levels through inhibition of NF-kappa B by enhancing PPAR gamma expression.Öğe Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells(Wiley, 2023) Hacioglu, Ceyhan; Kar, Fatih; Davran, Fatih; Tuncer, CengizGlioblastoma (GBM) is classified as a stage-IV glioma. Unfortunately, there are currently no curative treatments for GBM. Poly(rC)-binding protein 1 (PCBP1) is a cytosolic iron chaperone with diverse functions. PCBP1 is also known to regulate autophagy, but the role of PCBP1 in ferroptosis, iron-dependent cell death pathway, remains unrevealed in GBM cells. Here, we investigated the effects of borax, a boron compound, on the ferroptosis signaling pathway mediated by PCBP1 and autophagy. The study analyzed cell viability, proliferation, and cell cycle on U87-MG and HMC3 cells to investigate the effects of borax. After determining the cytotoxic concentrations of borax, morphological analyzes and measurement of PCBP1, Beclin1, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPx4) and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were performed. Finally, expression levels of PCBP1, Beclin1, GPx4 and ACSL4, and caspase-3/7 activity were determined. We found that borax reduced U87-MG cell viability in a concentration- and time-dependent manner. Additionally, borax altered cell proliferation and remarkably reduced S phase in the U87-MG cells and exhibited selectivity by having an opposite effect on normal cells (HMC3). According to DAPI staining, borax caused nuclear deficits in U87-MG cells. The result showed that borax in U87-MG cells induced reduction of the PCBP1, GSH, and GPx4 and enhancement of Beclin1, MDA, and ACSL4. Furthermore, borax triggered apoptosis by activating caspase 3/7 in U87-MG cells. Our study indicated that the borax has potential as an anticancer treatment for GBM via regulating PCBP1/Beclin1/GPx4/ACSL4 signaling pathways.Öğe Capsaicin induces redox imbalance and ferroptosis through ACSL4/GPx4 signaling pathways in U87-MG and U251 glioblastoma cells(Springer/Plenum Publishers, 2023) Hacıoğlu, Ceyhan; Kar, FatihGlioblastoma is one of the deadliest malignant gliomas. Capsaicin is a homovanillic acid derivative that can show anti-cancer effects by regulating various signaling pathways. The aim of this study is to investigate the effects of capsaicin on cell proliferation via ferroptosis in human U87-MG and U251 glioblastoma cells. Firstly, effects of capsaicin treatment on cell viability were determined by MTT analysis. Next, cellular-proliferation and cytotoxicity assays were determined by analyzing bromodeoxyuridine (BrdU) and lactate dehydrogenase (LDH) activity, respectively. Following, acyl-CoA synthetase long chain family member 4 (ACSL4), glutathione peroxidase 4 (GPx4), 5-hydroxyeicosatetraenoic acid (5-HETE), total oxidant status (TOS), malondialdehyde (MDA), total antioxidant status (TAS) and reduced glutathione (GSH) levels were determined by ELISA. Additionally, ACSL4 and GPx4 mRNA and protein levels were analyzed. Capsaicin showed a concentration-dependent anti-proliferative effects in U87-MG and U251 cells. Cell viability was decreased in the both cell lines treated with capsaicin concentrations above 50 mu M, while LDH activity increased. Treatment of 121.6, 188.5, and 237.2 mu M capsaicin concentrations for 24 h indicated an increase in ACSL4, 5-HETE, TOS and MDA levels in U87-MG and U251 cells (p < 0.05). On the other hand, we found that capsaicin administration caused a decrease in BrdU, GPx4, TAS and GSH levels in U87-MG and U251 cells (p < 0.05). Besides, ACSL4 mRNA and protein levels were increased in the glioblastoma cells treated with capsaicin, whereas GPx4 mRNA and protein levels were decreased. Finally, capsaicin might be used as a potential anticancer agent with ferroptosis-induced anti-proliferative effects in the treatment of human glioblastoma.Öğe Comparative effects of metformin and Cistus laurifolius L. extract in streptozotocin-induced diabetic rat model: oxidative, inflammatory, apoptotic, and histopathological analyzes(Springer Heidelberg, 2021) Hacioglu, Ceyhan; Kar, Fatih; Kara, Yakup; Yucel, Ersin; Donmez, Dilek Burukoglu; Senturk, Hakan; Kanbak, GungorInterest in phytochemical therapy methods in the treatment of diabetes is increasing day by day. Although the antidiabetic and antioxidant effects of Cistus laurifolius L. (CL) have been mentioned, the systemic effects remain unknown. The present study aims at evaluating the antidiabetic effects of the CL aqueous extract via metformin on streptozotocin (STZ)-induced diabetic rats. Forty male Wistar albino rats were divided into five groups of eight animals each: control, diabetic group (55mg/kg STZ), STZ+125mg/kg CL, STZ+250mg/kg CL, and STZ+100mg/kg metformin. The effects of CL and metformin on oxidative, apoptotic, and inflammatory pathways were comparatively investigated. In addition, nuclear factor-kappa B (NF kappa B), tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-1 beta expressions analysis were carried out. CL treatment resulted in a significant improvement in blood glucose levels, lipid profile, pancreatic markers, and liver and kidney function tests. A 250mg/kg CL treatment decreased by 67.9%, 31.6%, 66.8%, 28.3%, and 31.4% in the total oxidant capacity, NF kappa B, TNF-alpha, IL-1 beta, caspase3, and cytochrome c levels, respectively, compared to the diabetic group. Additionally, CL treatments showed a dose-dependent reduction in NF kappa B, TNF-alpha, and IL-1 beta expression levels. A 250mg/kg CL treatment exhibited a greater increase (by 9.6%) in total antioxidant capacity than metformin. CL treatment provided histologically more improvement in the brain, heart, pancreas, spleen, liver, kidney, and testicular tissues compared to the metformin group. Our results suggest that the single treatment of CL aqueous extract at the low doses may have stronger short-term anti-diabetic effects than metformin. Therefore, further studies are needed regarding the long-term hypoglycemic effect or treatment of CL aqueous extract.Öğe Concanavalin A induces apoptosis in a dose-dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells(Wiley, 2021) Kar, Fatih; Kacar, Sedat; Hacioglu, Ceyhan; Kanbak, Gungor; Sahinturk, VarolGlioma is the most common brain tumor. C6 rat glioblastoma cells provide the possibility to the scientist to study brain cancer. Concanavalin A (Con A) has a lot of antitumoral effects, especially over oxidative stress. In the present study, it was aimed to decide the impacts of various doses of Con A on C6 glioblastoma cells regarding cytotoxicity, thiol/disulfide homeostasis, apoptosis, and inflammation. We detected the cytotoxic activity of Con A (from 7.8 to 500 mu g/ml) in C6 cells by utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and determined the toxic concentration of Con A. Once the optimal doses were found, the thiol-disulfide homeostasis, levels of total antioxidant and oxidant status (TAS and TOS), malondialdehyde (MDA) and glutathione (GSH), pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), apoptotic proteins as cytochrome c (CYCS), and caspase 3 (CASP3) were measured. Apoptotic and morphological changes in the C6 cells were examined with an inverted microscope and flow cytometry technique. Dose-dependent Con A triggered oxidative damage in the C6 cells, affecting the inflammatory pathway, so reducing proliferation with apoptotic proteins and morphological changes. But especially, Con A increased disulfide formation by disrupting the thiol/disulfide balance in C6 cells. This study revealed that Con A, known as carbohydrate-binding protein, generated oxidative damage, inflammation, and apoptosis in a dose-dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells.Öğe Concentration-Dependent Effects of Zinc Sulfate on DU-145 Human Prostate Cancer Cell Line: Oxidative, Apoptotic, Inflammatory, and Morphological Analyzes(Humana Press Inc., 2019) Hacıoğlu, Ceyhan; Kaçar, Sedat; Kar, Fatih; Kanbak, Güngör; Şahintürk, VarolZinc takes part in several of cellular signaling pathways, containing defense against free radicals, apoptosis, and inflammation. However, interaction between zinc and prostate cancer progression is poorly understood. Therefore, zinc treatment in DU-145 human prostate cancer cells was investigated. First, zinc sulfate (ZnSO4) concentrations with antiproliferative effect were determined using MTT assay. Then, ZnSO4-induced oxidative damage was evaluated by malondialdehyde (MDA) levels, glutathione (GSH) levels, total oxidant status (TOS) levels, and total antioxidant status (TAS) levels. Apoptotic effects of ZnSO4 were determined by measuring biochemical and immunohistochemical parameters including caspase 3 (CASP3), cytochrome C (CYC), Bcl-2-associated X protein (Bax), and B cell CLL/lymphoma 2 (Bcl-2) levels. Inflammatory effects of ZnSO4 were investigated by measuring interleukin-6 (IL-6) levels and tumor necrosis factor-alpha (TNF-?) levels. Finally, morphological analysis was performed using hematoxylin-eosin staining. We found that ZnSO4 caused a concentration-dependent increase in oxidative stress, apoptosis, and inflammation pathways. Moreover, there were a number of morphological alterations in treated cells depending on the ZnSO4 concentration. Consequently, our data showed that zinc acts as a regulator of increased oxidative damage and apoptosis through the upregulation of TNF-? and IL-6. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.Öğe Curcumin Acts as Post-protective Effects on Rat Hippocampal Synaptosomes in a Neuronal Model of Aluminum-Induced Toxicity(Springer/Plenum Publishers, 2019) Kar, Fatih; Hacıoğlu, Ceyhan; Uslu, Sema; Kanbak, GüngörThe neurotoxic effects of aluminum are generally associated with reduced antioxidant capacity, increased oxidative stress and apoptosis, which lead to the induction of neurodegenerative processes. Curcumin has a lipophilic polyphenol character and effects of antioxidant and anti-apoptotic. The present study was undertaken to examine possible aluminum exposure in rats brain synaptosomes and to investigate whether protective and therapeutic effects of curcumin on biochemical and morphological changes in both pre- and post-treated groups. Aluminum chloride (AlCl3) at 50 mu M concentration and curcumin at 5 and 10 mu g/mL doses were applied to hippocampal synaptosomes of rats according to experimental design. Biochemical effects were evaluated by MTT cytotoxicity, malondialdehyde (MDA) levels, nitric oxide (NO) levels, glutathione (GSH) levels, caspase 3 activities, cytochrome c levels, DNA fragmentation values and protein levels. Morphological examinations were done by TEM analysis. AlCI3 exposure in the synaptosomes enhanced oxidative stress, triggered apoptosis and caused ultrastructural alterations which were well reflected in the TEM images. Curcumin pre-treatment slightly ameliorated the MDA levels, NO levels, cytochrome c levels and caspase 3 activities in AlCI3-exposed synaptosomes, but these results were not statistically significant. Furthermore, curcumin post-treatment significantly improved oxidative damage and morphological alterations, and suppressed cytochrome c and caspase 3 activities. Taken together, our data showed that curcumin had more therapeutic effects than protective effects in AlCI3-induced neurotoxicity. Nevertheless, the therapeutic (post-protective) effects of curcumin should be further investigated in in vivo neurodegenerative models involving behavioral tests.Öğe Curcumin and LOXblock-1 ameliorate ischemia-reperfusion induced inflammation and acute kidney injury by suppressing the semaphorin-plexin pathway(Pergamon-Elsevier Science Ltd, 2020) Kar, Fatih; Hacioglu, Ceyhan; Senturk, Hakan; Donmez, Dilek Burukoglu; Kanbak, Gungor; Uslu, SemaAims: Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway. Main methods: The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 mu g/kg, i.p.). Key findings: The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-alpha, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury. Significance: The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.Öğe Cyproheptadine causes apoptosis and decreases inflammation by disrupting thiol/disulfide balance and enhancing the levels of SIRT1 in C6 glioblastoma cells(Pergamon-Elsevier Science Ltd, 2021) Kacar, Sedat; Hacioglu, Ceyhan; Kar, Fatih; Sahinturk, Varol; Kanbak, GungorCyproheptadine is first-generation antihistamine drug, that is, H1 receptor antagonist, with a drug being anesthetic, anti-serotonergic and anti-cholinergic and started to be used clinically in the 1960s. As firstly utilized as an anti-allergic drug, usage of cyproheptadine was expanded to other cases including serotonin syndrome, appetite increasing, migraines and insomnia. However, there are almost few studies seeking to explore the association between cyproheptadine and cancer in general. In the present study, we sought to determine the impact of cyproheptadine on C6 glioblastoma cells by morphological, biochemical and cytotoxic analyzes. We searched the effective doses of cyproheptadine for C6 glioblastoma cells and examined the cells under an inverted microscope. Next, we determined the protein levels of SIRT1, NF?B and IL-6 protein. Then, we measured and calculated the levels of thiols, disulfide bonds and related parameters. After that, we evaluated apoptotic activity by Annexin V and caspase 3 assays. As a result, we detected a dose-dependent increase in apoptosis and SIRT 1 protein levels, and a decrease in inflammatory proteins. Furthermore, we have detected a drop in thiol and disulfide content. Our study suggests that Cyproheptadine causes apoptosis and decreases inflammation by disrupting thiol/disulfide balance and enhancing the levels of SIRT1, offering the potential for being an anticancer drug. Therefore, it might be further investigated in future studies.Öğe The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways(Wiley, 2023) Kar, Fatih; Hacıoğlu, Ceyhan; Kaçar, SedatGlioblastoma multiform (GBM) is a malignant tumor cancer that originates from the star-shaped glial support tissues, namely astrocytes, and it is associated with a poor prognosis in the brain. The GBM has no cure, and chemotherapy, radiation therapy, and immunotherapy are all ineffective. A certain dose of Boric acid (BA) has many biochemical effects, conspicuously over antioxidant/oxidant rates. This article sought to investigate the modifies of various doses of BA on the glioblastoma concerning cytotoxicity, ferroptosis, apoptosis, and semaphorin-neuropilin signaling pathway. The Cytotoxic activity and cell viability of BA (0.39-25 mM) in C6 cells were tested at 24, 48, and 72 h using 3-(4,5-dimethylthiazol, 2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The IC50 concentration of BA at 1.56 mM was found and cell lysate used for biochemical analysis. Glutathione peroxidase 4 (GPx4) and ACLS4 levels of ferroptosis, levels of total antioxidant (TAS) and oxidant (TAS) parameters, malondialdehyde (MDA), apoptotic proteins as caspase 3 (CASP3) and caspase 7 (CASP7) were measured. The ferroptosis, semaphoring-neuropilin, apoptotic pathway markers and cell counts were analyzed with flow cytometry, Q-PCR, Western and Elisa technique in the C6 cell lysate. BA triggered ferroptosis in the C6 cells dose-dependently, affecting the semaphorin pathway, so reducing proliferation with apoptotic compared with untreated cell as control group (p < .05). This study revealed that BA, defined as trace element and natural compound, incubated ferroptosis, total oxidant molecules, and caspase protein in a dose-dependently by disrupting SEMA3F in tumor cells.Öğe Effects of Curcumin and Boric Acid Against Neurodegenerative Damage Induced by Amyloid Beta (1-42)(Humana Press Inc, 2021) Hacioglu, Ceyhan; Kar, Fatih; Kar, Ezgi; Kara, Yakup; Kanbak, GungorSynaptosomes are used as an ex vivo model in the investigation of neuronal transmission and neurodegenerative processes. In this study, we aimed to determine the protective effects of boric acid (BA) and curcumin, which have antioxidant and anti-inflammatory properties, on A beta 1-42 induced neurodegenerative damage. Synaptosomes obtained from the rat cerebral cortex were divided into five groups: control, 10 mu M A beta 1-42, 10 mu M A beta 1-42 + 25 mM BA, 10 mu M A beta 1-42 + 10 mu M curcumin, and 10 mu M A beta 1-42 + 25 mM BA+10 mu M curcumin. Synaptosomes treated with A beta 1-42 caused a significant decline in synaptophysin levels and increase in malondialdehyde (MDA) levels, acetylcholinesterase (AChE) activities, DNA fragmentation values, and nitric oxide (NO) levels compared with the control group (P < 0.01). Synaptosomes treated with BA showed a significant reduction in MDA and NO levels against A beta 1-42 exposure (P < 0.01). In addition, curcumin treatment has been found to cause a significant reduction in AChE activities and MDA levels in synaptosomes (P < 0.05). Co-administration of BA and curcumin on synaptosomes exposed to A beta 1-42 resulted in a significant decrease in DNA fragmentation values, MDA levels, and AChE activities. Curcumin and BA + curcumin combination showed an enhancement in synaptophysin levels of A beta 1-42-induced synaptosomes (P < 0.01). The results showed that BA and curcumin had protective effects on rat brain synaptosomes against A beta 1-42 exposure. BA and curcumin treatment can have abilities to prevent the alterations of the cholinergic system and inhibit oxidative stress in the cerebral cortex synapses of A beta 1-42 exposed.Öğe Ex vivo investigation of betaine and boric acid function as preprotective agents on rat synaptosomes to be treated with A? (1-42)(Wiley, 2024) Hacioglu, Ceyhan; Kar, Fatih; Ozbayer, Cansu; Gundogdu, Ayse CakirRecent evidence suggests that ferroptosis, an iron-dependent cell death process, may be involved in Alzheimer's disease (AD) pathology. The study evaluated the therapeutic potential of betaine and boric acid (BA) pretreatment administered to rats for 21 days in AD. Then, the rats were sacrificed, and morphological and biochemical analyses were performed in brain tissues. Next, an ex vivo AD model was created by applying amyloid-beta (A beta 1-42) to synaptosomes isolated from the brain tissues. Synaptosomes were analyzed with micrograph images, and protein and mRNA levels of ferroptotic markers were determined. Betaine and BA pretreatments did not cause any morphological and biochemical differences in the brain tissue. However, A beta (1-42) administration in synaptosomes increased the levels of acyl-CoA synthetase long chain family member-4 (ACSL4), transferrin receptor-1 protein (TfR1), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and decreased the levels glutathione peroxidase-4 (GPx4) and glutathione (GSH). Moreover, ACSL4, GPx4, and TfR1 mRNA and protein levels were similar to the ELISA results. In contrast, betaine and BA pretreatments decreased the levels of ACSL4, TfR1, MDA, and 8-OHdG in synaptosomes incubated with A beta 1-42, while promoting increased levels of GPx4 and GSH. In addition, betaine and BA pretreatments completely reversed ACSL4, GPx4, and TfR1 mRNA and protein levels. Therefore, betaine and BA pretreatments may contribute to the prevention of neurodegenerative damage by supporting antiferroptotic activities.Öğe Ex Vivo Investigation of Bexarotene and Nicotinamide Function as a Protective Agent on Rat Synaptosomes Treated with A beta(1-42)(Springer/Plenum Publishers, 2021) Hacioglu, Ceyhan; Kar, Fatih; Kanbak, GungorIn this study, we were aimed to investigate the neuroprotective effects of bexarotene and nicotinamide in synaptosomes incubated with amyloid-beta (A beta). Our study consists of 2 parts, in vivo and in vitro. In the in vivo section, twenty-four Wistar albino male rats were divided into 4 groups (control, dimethyl sulfoxide (DMSO), nicotinamide and bexarotene) with six animals in each group. DMSO(1%), nicotinamide(100 mg/kg) and bexarotene(0.1 mg/kg) were administered intraperitoneally to animals in the experimental groups for seven days. In the in vitro part of our study, three different isolation methods were used to obtain the synaptosomes from the brain tissue. Total antioxidant capacity(TAS), total oxidant capacity(TOS), cleaved caspase 3(CASP3), cytochrome c(Cyt c), sirtuin 1(SIRT1), peroxisome proliferator-activated receptor gamma(PPAR gamma) and poly(ADP-ribose) polymerase-1(PARP-1) levels in the synaptosomes incubated with a concentration of 10 mu M A beta(1-42) were measured by enzyme-linked immunosorbent assay method. Biochemical analysis and histopathological examinations in serum and brain samples showed that DMSO, nicotinamide and bexarotene treatments did not cause any damage to the rat brain tissue. We found that in vitro A beta(1-42) administration decreased TAS, SIRT1 and PPAR gamma levels in synaptosomes while increasing TOS, CASP3, Cyt c, and PARP1 levels. Nicotinamide treatment suppressed oxidative stress and apoptosis by supporting antioxidant capacity and increased PPAR gamma through SIRT1 activation, causing PARP1 to decrease. On the other hand, bexarotene caused a moderate increase in SIRT1 levels with PPAR gamma activation. Consequently, we found that nicotinamide can be more effective than bexarotene in AD pathogenesis by regulating mitochondrial functions in synaptosomes.Öğe High Concentrations of Boric Acid Trigger Concentration-Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line(Humana Press Inc, 2020) Hacioglu, Ceyhan; Kar, Fatih; Kacar, Sedat; Sahinturk, Varol; Kanbak, GungorBoric acid is known to regulate the proliferation of cancer cells. Prostate cancer is among the types of cancer with high mortality in men. There are a few numbers of studies investigating the effects of boric acid on prostate cancer cells. The objective of the present study was to assess the effects of boric acid at concentrations higher than that can be achieved in blood by dietary intake on DU-145 human prostate cancer cells for 24 h. Firstly, we determined the cytotoxic activity of boric acid (0 to 12.5 mM) on DU-145 human prostate cancer cells by using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and defined the IC50 concentration of boric acid. Then, by employing the doses found in MTT, the levels of antioxidant-oxidant molecules and apoptotic proteins were measured and morphological changes were evaluated. We have concluded that boric acid caused oxidative stress, inhibition of cell growth, apoptosis, and morphological alterations in a concentration-dependent manner in DU-145 cells. Furthermore, treatments with increasing boric acid concentrations decreased the antioxidant levels in cells. We actually revealed that boric acid, known as an antioxidant, may prevent cell proliferation by acting as an oxidant in certain doses. Although the high IC50 concentration of boric acid is perceived to be negative, we think it provides important background for subsequent studies.Öğe In Vivo Assessment of the Effect of Hexagonal Boron Nitride Nanoparticles on Biochemical, Histopathological, Oxidant and Antioxidant Status(Springer/Plenum Publishers, 2021) Kar, Fatih; Hacioglu, Ceyhan; Goncu, Yapincak; Sogut, Ibrahim; Senturk, Hakan; Donmez, Dilek Burukoglu; Ay, NuranThe aim of our study is to investigate the dose-dependent biological system effect of hexagonal boron nitride (hBN) nanoparticles, which is directly produced nanoscale, in vivo. Wistar albino rats (n = 80) weighing 200-250 g were divided into eight groups (n = 10). The acute effects of hBN NPs (i.v) on the rats were investigated by measuring the biochemical, hematological parameters and oxidant-antioxidant status. The results show that no significant change was observed in the hematological and biochemical parameters when the control group and other low dose groups were compared, except for the 1600 and 3200 mu g/kg b.w. dose groups. Histological detection indicated that 1600 and 3200 mu g/kg hBN NPs treatment could induce significant damage in the liver, kidney, heart, spleen and pancreas. With the findings obtained, it can be seen that hBN NPs cannot be evaluated independently of particle morphology, and that the hBN NPs used in this study may be suitable for biomedical applications where low doses between 50 and 800 mu g/kg are not toxic.Öğe Irradiated riboflavin over nonradiated one: Potent antimigratory, antiproliferative and cytotoxic effects on glioblastoma cells(Wiley, 2024) Kacar, Sedat; Hacioglu, Ceyhan; Kar, FatihRiboflavin is a water-soluble yellowish vitamin and is controversial regarding its effect on tumour cells. Riboflavin is a powerful photosensitizer that upon exposure to radiation, undergoes an intersystem conversion with molecular oxygen, leading to the production of ROS. In the current study, we sought to ascertain the impact of irradiated riboflavin on C6 glioblastoma cells regarding proliferation, cell death, oxidative stress and migration. First, we compared the proliferative behaviour of cells following nonradiated and radiated riboflavin. Next, we performed apoptotic assays including Annexin V and caspase 3, 7 and 9 assays. Then we checked on oxidative stress and status by flow cytometry and ELISA kits. Finally, we examined inflammatory change and levels of MMP2 and SIRT1 proteins. We caught a clear antiproliferative and cytotoxic effect of irradiated riboflavin compared to nonradiated one. Therefore, we proceeded with our experiments using radiated riboflavin. In all apoptotic assays, we observed a dose-dependent increase. Additionally, the levels of oxidants were found to increase, while antioxidant levels decreased following riboflavin treatment. In the inflammation analysis, we observed elevated levels of both pro-inflammatory and anti-inflammatory cytokines. Additionally, after treatment, we observed reduced levels of MMP2 and SIRT. In conclusion, radiated riboflavin clearly demonstrates superior antiproliferative and apoptotic effects on C6 cells at lower doses compared to nonradiated riboflavin.Öğe Kurkumin’in U251 hücrelerinde antineoplastik potansiyellerinin mekanizması olarak anti-oksidatif ve apoptotik özellikleri(2021) Kar, Fatih; Hacıoğlu, CeyhanGlioblastoma beyin kanser türleri arasında en agresif olanıdır. Özellikle kanser araştırmalarında in vitro çalışmalar ile yeni ilaç adaylarının etkinliği araştırılmaktadır. Bu çalışma ile U251 hücreleri üzerinde farklı dozlarda kurkumin uygulamasının antineoplastik etkilerini araştırmayı amaçladık. Kurkumin’in, prooksidan-antioksidan mekanizmaları modüle ederek ROS üretimini, apoptoz aktivitesini ve inflamasyonu tetikleyerek U251 hücre canlılığını inhibe ettiğini varsayıyoruz. Bu çalışmada, IL-1?, TNF-?, kaspaz 3/9 seviyeleri, toplam antioksidan (TAS) ve toplam oksidan seviyeleri (TOS) ölçüldü. MTT ile hücre canlılıkları belirlendi ve 10, 20 ve 40 µM kurkumin dozlarının efektif dozlar olduğu tespit edildi. 40 µM kurkumin uygulamasının kontrol grubu ve diğer doz grupları ile karşılaştırıldığında oksidatif stresi, inflamasyonu ve apoptozu indüklediği bulundu (p<0.05). 10 µM kurkumin grubunda istatistiksel olarak fark tespit edilmedi. 40 µM kurkuminin U251 glioblastoma hücrelerinin proliferasyonu ve migrasyonu üzerinde doza bağlı bir etkiye sahip olduğunu ve proliferasyonunu önemli ölçüde inhibe ettiğini buldukÖğe LoxBlock-1 or Curcumin attenuates liver, pancreas and cardiac ferroptosis, oxidative stress and injury in Ischemia/reperfusion-damaged rats by facilitating ACSL/GPx4 signaling(Churchill Livingstone, 2023) Kar, Fatih; Yildiz, Fatma; Hacioglu, Ceyhan; Kar, Ezgi; Donmez, Dilek Burukoglu; Senturk, Hakan; Kanbak, GungorIn this study, the effects of the pretreatment of Curcumin and LoxBlock-1 on liver, pancreas, and cardiac dysfunction following Ischemia-Reperfusion-induced (IR) Acute Kidney Injury (AKI) were investigated through the mechanisms of oxidative stress and ferroptosis. Total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) parameters in the tissue were analyzed to investigate the oxidative stress occurring in the liver, pancreas, and heart, and Acyl-Coa synthetase long-chain family member (ACSL4). Glutathione peroxidase 4 (GPx4) enzyme levels were also analyzed by ELISA to investigate the effect on ferroptosis. In addition, hematoxylin-eosin staining was performed for histopathological examination of the tissues. As a result of biochemical analyzes, it was observed that oxidative stress parameters increased significantly in the IR group. In addition, while the ACSL4 enzyme level increased in the IR group in all tissues, the GPx4 enzyme level decreased. In the histopathological examination, it was observed that IR caused serious damage to the heart, liver, and pancreas tissues. The present study shows that Curcumin and LoxBlock-1 have a protective effect on the liver, pancreas, and cardiac ferroptosis following the effect on AKI. In addition, Curcumin was found to be more effective than LoxBlock-1 in I/R injury with its antioxidant property.
