DSpace Arşivi :: by Yazar "Hacioglu, Ceyhan" değerine göre listeleniyor

Yazar "Hacioglu, Ceyhan" seçeneğine göre listele

Listeleniyor 1 - 20 / 21

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, Gungor
Gliomas 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.
Borax affects cellular viability by inducing ER stress in hepatocellular carcinoma cells by targeting SLC12A5
(Wiley, 2024) Hacioglu, Ceyhan; Oral, Didem
Hepatocellular carcinoma (HCC) presents a persistent challenge to conventional therapeutic approaches. SLC12A5 is implicated in an oncogenic capacity and facilitates the progression of cancer. The objective of this investigation is to scrutinize the inhibitory effects of borax on endoplasmic reticulum (ER)-stress and apoptosis mediated by SLC12A5 in HepG2 cells. Initially, we evaluated the cytotoxic impact of borax on both HL-7702 and HepG2 cell lines. Subsequently, the effects of borax on cellular morphology and the cell cycle of these lines were examined. Following this, we explored the impact of borax treatment on the mRNA and protein expression levels of SLC12A5, C/EBP homologous protein (CHOP), glucose-regulated protein-78 (GRP78), activating transcription factor-6 (ATF6), caspase-3 (CASP3), and cytochrome c (CYC) in these cellular populations. The determined IC50 value of borax for HL-7702 cells was 40.8 mM, whereas for HepG2 cells, this value was 22.6 mM. The concentrations of IC50 (22.6 mM) and IC75 (45.7 mM) of borax in HepG2 cells did not manifest morphological aberrations in HL-7702 cells. Conversely, these concentrations in HepG2 cells induced observable morphological and nuclear abnormalities, resulting in cell cycle arrest in the G1/G0 phase. Additionally, the levels of SLC12A5, ATF6, CHOP, GRP78, CASP3, and CYC were elevated in HepG2 cells in comparison to HL-7702 cells. Moreover, SLC12A5 levels decreased following borax treatment in HepG2 cells, whereas ATF6, CHOP, GRP78, CASP3, and CYC levels exhibited a significant increase. In conclusion, our data highlight the potential therapeutic effects of borax through the regulation of ER stress in HCC by targeting SLC12A5.
Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways
(Wiley, 2024) Tuncer, Cengiz; Hacioglu, Ceyhan
Glioblastoma multiforme (GBM) is a highly aggressive and lethal form of primary brain tumour. Borax has been demonstrated to exhibit anti-cancer activity through cell death pathways. However, the specific impact of borax on ferroptosis in GBM is not well-established, and the underlying regulatory mechanisms remain unclear. Initially, the effective concentration of borax on cell viability and proliferation in U251 and A172 cells was determined. Subsequently, the effects of borax on the wound healing were analysed. Nuclear factor erythroid 2-related factor 2 (NRF2), glutathione peroxidase 4 (GPx4), glutathione (GSH), HSP70 protein 5 (HSPA5), malondialdehyde (MDA) levels and caspase-3/7 activity were determined in borax-treated and untreated cells. Finally, the protein expression levels of HSPA5, NRF2 and GPx4 were analysed. Borax suppressed cell viability and proliferation in U251 and A172 cells in a concentration- and time-dependent manner. In addition, borax treatment decreased GPx4, GSH, HSPA5 and NRF2 levels in U251 and A172 cells while increasing MDA levels and caspase-3/7 activity. Moreover, borax reduced mRNA and protein levels of HSPA5, NRF2 and GPx4 in U251 and A172 cells. Consequently, borax may induce ferroptosis in GBM cells and regulate the associated regulatory mechanisms targeting NRF2 and HSPA5 pathways. This knowledge may contribute to the development of novel therapeutic approaches targeting ferroptosis in GBM and potentially improve patient outcomes.
Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells
(Wiley, 2023) Hacioglu, Ceyhan; Kar, Fatih; Davran, Fatih; Tuncer, Cengiz
Glioblastoma (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.
Boric acid Increases Susceptibility to Chemotherapy by Targeting the Ferritinophagy Signaling Pathway in TMZ Resistant Glioblastoma Cells
(Springernature, 2024) Hacioglu, Ceyhan; Tuncer, Cengiz
Glioblastoma (GBM) is a common and highly lethal form of brain cancer. Temozolomide (TMZ) is the primary chemotherapy used for GBM, but it has limited effectiveness, with about half of the patients developing resistance. Iron regulatory proteins (IRPs) modulate genes involved in iron metabolism, while the nuclear receptor coactivator 4 (NCOA4) controls iron metabolism through a process called ferritinophagy. In this study, we investigated whether boric acid increases chemosensitivity mediated by ferritinophagy via the NCOA4 and IRP2 signaling pathways in TMZ-resistant GBM cells. First, we generated TMZ-resistant GBM cells (A172-R and T98G-R cells). Next, we investigated the effects of boric acid on cell viability, proliferation, cell cycle, and cell morphology in these cells. Additionally, following boric acid treatment, we analyzed the expression and protein levels of various biochemical markers in these cells. Boric acid treatment in A172-R and T98G-R cells suppressed cell viability and proliferation, arrested these cells in the G1/G0 cell cycle, and induced morphological differences. Boric acid increased NCOA4, IRP2, iron, and malondialdehyde (MDA) levels in A172-R and T98G-R cells, while glutathione (GSH) and glutathione peroxidase 4 (GPx4) levels decreased. Moreover, boric acid treatment increased intracellular iron levels and lipid peroxidation by inducing NCOA4 and IRP2 expression levels in TMZ-resistant cells. According to our results, boric acid may regulate chemosensitivity in A172-R and T98G-R cells mediated by NCOA4 and IRP2. In conclusion, the manipulative effects of boric acid on the ferritinophagy pathway hold the potential to sensitize TMZ-resistant GBM cells to chemotherapy.
Capsaicin Enhances Temozolomide-Resistant Glioblastoma Cells' Chemosensitivity and Ferroptosis through FHOD1/IRF2 Downregulation
(Wiley-Hindawi, 2024) Hacioglu, Ceyhan
Resistance of tumor cells to chemotherapy, particularly in the case of glioblastoma (GBM), a common brain tumor, presents a substantial challenge in oncology. In this study, we investigated the potential of capsaicin to overcome drug resistance in temozolomide (TMZ)-resistant U87 and U251 cells by targeting ferroptosis-mediated interferon regulatory factor (IRF)-2 and formin homology-2 domain-containing protein-1 (FHOD1) signal pathways. First, we induced TMZ resistance in these cells by treating them with TMZ for three weeks. Subsequently, we assessed the impacts of capsaicin on various aspects, including cell viability, proliferation, ferroptosis markers, levels of IRF2 and FHOD1, intracellular iron concentrations, and cell migration in these cells. Our results indicate that capsaicin treatment resulted in a significant decrease in both cell viability and proliferation in TMZ-resistant U87-R and U251-R cells. In addition, it effectively suppressed cell migration rates in these cells, targeting TMZ resistance. Furthermore, capsaicin demonstrated its ability to downregulate FHOD1, IRF2, glutathione, and glutathione peroxidase 4 levels in TMZ-resistant cells. This was accompanied by an increase in intracellular iron, total oxidant status, and increased malondialdehyde levels. Significantly, the treatment with capsaicin led to a notable decrease in the expressions of FHOD1 and IRF2 at both the mRNA and protein levels in U87-R and U251-R cells. In summary, our results emphasize the substantial potential of capsaicin in enhancing the sensitivity of TMZ-resistant GBM cells to chemotherapy. This effect is achieved through its modulation of ferroptosis-related pathways, involving the regulation of FHOD1 and IRF2 expressions.
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, Gungor
Interest 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.
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, Varol
Glioma 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.
Correlation of perilipin 2 and lipid metabolism in elective cesarean section and vaginal delivery: a prospective study with oxidative and apoptotic pathways
(Springer, 2021) Hacioglu, Ceyhan; Sahin, Ibrahim Ethem; Uyuk, Can
Vaginal delivery (VD) and elective cesarean (CS) delivery modes may cause significant differences in maternal and fetal metabolism. In this study, we aimed to investigate changes in lipid metabolism, oxidative and apoptotic signaling pathways during VD and CS in maternal and cord blood and placenta tissue. The study included two groups of participants delivered via 90 CS and 90 VD. Maternal and cord blood samples were collected from the participants. In addition, placenta samples were also taken after delivery. Total oxidant (TOS), malondialdehyde (MDA), total antioxidant (TAS), glutathione (GSH), cleaved caspase 3 (CASP3) and perilipin 2 (PLIN2) levels were measured to determine oxidative stress, antioxidant levels and apoptosis status in the VD and CS groups. Besides, PLIN2 mRNA expressions in placental specimens were analyzed. We found no statistically significant difference in maternal age, body mass index, gestational age, birth weight and Apgar scores in both groups (P > 0.05). The increase in MDA, TOS, GSH and TAS levels was higher in the VD group compared to the CS group (P < 0.05). Similarly, PLIN2 levels and lipid profiles showed an increase in the VD group (P < 0.05 vs CS group). Likewise, PLIN2 expression enhanced in the VD group (P < 0.05 vs CS group). However, CASP3 activity reduced in maternal and cord blood in the VD group compared to the CS group. Our results support that the delivery mode may cause differences in lipid profile, oxidative and apoptotic status by affecting PLIN2 levels in both maternal and cord blood and placenta tissue.
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, Sema
Aims: 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.
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, Gungor
Cyproheptadine 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.
The Effect of Vitamin D Level on the Clinical Situation in COVID-19 Patients
(Duzce Univ, Fac Medicine, 2023) Davran, Fatih; Hacioglu, Ceyhan; Kayabasi, Eda; Keskin, Banu Humeyra; Duran, Pelin Kamuran; Unlu, Nisa; Escan, Elif
Objective: Vitamin D plays an important role in maintaining the integrity of mucosal barriers and in natural and acquired immunity. In the COVID-19 pandemic, the strength of personal immunity is very important in the course of the disease, despite the presence of variants of the virus or vaccination status. Method: In this study, we investigated the relationship between the clinical course and vitamin D levels of outpatient and inpatient follow-up patients admitted to our hospital due to COVID-19. A total of 94 patients, 47 outpatients and 47 inpatients, were included in the study. Results: The mean age and gender distributions of both groups were similar. Vitamin D levels were found to be normal in only 7 of 94 patients who were followed up in our hospital due to COVID-19. Patients with vitamin D levels >= 30 were significantly lower than those with <10 and 10-29.9 (p<0.01 for each). Hospitalized patients (71%) with vitamin D levels <10 were significantly higher than those (0%) with vitamin D levels >= 30. Additionally, the outpatients (29%) with vitamin D levels <10 were significantly lower than those (100%) with vitamin D levels >= 30. Conclusion: The data showed that vitamin D deficiency may be associated with the severe clinical course of COVID-19, even in patients without comorbidities, and may also be one of the predisposing factors resulting in death in COVID-19. As a result, vitamin D levels in COVID-19 patients may be important for the course of the disease.
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, Gungor
Synaptosomes 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.
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 Cakir
Recent 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.
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, Gungor
In 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.
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, Gungor
Boric 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.
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, Nuran
The 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.
Irradiated riboflavin over nonradiated one: Potent antimigratory, antiproliferative and cytotoxic effects on glioblastoma cells
(Wiley, 2024) Kacar, Sedat; Hacioglu, Ceyhan; Kar, Fatih
Riboflavin 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.
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, Gungor
In 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.
Neurochemical Research of LOXBlock-1 and ZnSO4 against Neurodegenerative Damage Induced by Amyloid Beta(1-42)
(Springernature, 2024) Hacioglu, Ceyhan; Kar, Fatih; Sahin, Meryem Cansu
Synaptosomes offer an intriguing ex vivo model system for investigating the molecular mechanisms of neurodegenerative processes. Lipoxygenases significantly affect the course of neurodegenerative diseases. Homeostasis of trace elements such as zinc is necessary for the continuity of brain functions. In this study, we purpose to determine whether LOXBlock-1, a 12/15 lipoxygenase inhibitor, and zinc sulfate (ZnSO4) provide any biochemical protection during neurodegenerative damage in synaptosomes induced by amyloid beta 1-42 (A beta 1-42). In this study, animals (30 Wistar Albino male rats 30) were divided into 5 groups (6 animals in each group): Control, 10 mu M A beta 1-42, 10 mu M A beta 1-42+25mM LOXBlock-1, 10 mu M A beta 1-42+10 mu M ZnSO4, and 10 mu M A beta 1-42+25mM LOXBlock-1+10 mu M ZnSO4. Synaptosomes were isolated from the rat cerebral cortex. Following, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, malondialdehyde (MDA) levels, adenosine deaminase (ADA) levels, reduced-glutathione (GSH) levels, neuronal nitric oxide synthase (nNOS) levels, acetylcholinesterase (AChE) activity, catalase (CAT) activity, and 8-OHdG levels in synaptosomes were detected according to the ELISA method. ADA and AChE expression and protein levels were analyzed. MDA, nNOS, AChE, and 8-OHdG levels in synaptosomes treated with A beta 1-42 resulted in an increase, while there was a decrease in ADA, GSH, and CAT levels (p<0.001 vs. control). Conversely, LOXBlock-1 and ZnSO4 treatments in synaptosomes treated with A beta 1-42 decreased MDA, nNOS, AChE, and 8-OHdG levels, while ADA, GSH, and CAT levels increased. Moreover, the most effective improvement was seen in the co-treatment group of LOXBlock-1 and ZnSO4. Our data showed that LOXBlock-1 and ZnSO4 co-treatment may protect against A beta 1-42 exposure in rat brain synaptosomes.

Yazar "Hacioglu, Ceyhan" seçeneğine göre listele

Sayfa Başına Sonuç

Sıralama seçenekleri