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    Ameliorative effects of agomelatine against doxorubicin-induced hepatotoxicity
    (Bmc, 2025) Savas, Hasan Basri; Sozen, Mehmet Enes; Cuce, Gokhan; Batur, Tuba
    Drug-induced hepatotoxicity is a significant impediment to the use of doxorubicin, a commonly employed chemotherapeutic agent with established efficacy in cancer treatment. The present study aimed to determine the potential protective effects of agomelatine against doxorubicin hepatotoxicity in rat toxicity models. Thirty-two rats were divided into four groups: control (with saline administration), Doxo (with 40 mg/kg doxorubicin administration), Doxo + Ago20, and Doxo + Ago40 (with 20 and 40 mg/kg agomelatine administration and 40 mg/kg doxorubicin administration). On the day of 14 rats were sacrificed, samples were collected for comparison of immunohistochemical, hematological, and biochemical analysis. There were statistically significant differences between the study groups in terms of immunohistochemical, hematological, and biochemical parameters. Agomelatine administration reduced the TNF-alpha, and caspase-3, which increased by doxorubicin, and reversed levels of oxidative stress markers altered by doxorubicin (p < 0.05). Doxorubicin induces oxidative stress, apoptosis, and hepatotoxicity. Agomelatine may be favored as a primary antidepressant to mitigate hepatic damage induced by doxorubicin.
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    Elevated level of neuroserpin is an indication for the resistance to gambogic acid-induced apoptosis and oxidative stress in triple-negative breast cancer cells
    (Walter De Gruyter Gmbh, 2024) Kucuksayan, Ertan; Kucuksayan, Hakan; Sozen, Mehmet Enes; Sircan-Kucuksayan, Aslinur
    Background: The triple-negative breast cancer (TNBC) subtype, characterized by loss of HER2, estrogen, and progesterone receptors, displays aggressive phenotype and poor prognosis compared to other BC subtypes. Since the TNBC cells are devoid of receptors, endocrine therapy is an ineffective option for TNBC patients, necessitating canonical chemotherapy strategies to treat TNBC. It is crucial to use alternative and natural agents to support chemotherapy in TNBC. Objectives: To clarify the molecular mechanism of the tumorigenic effects of gambogic acid (GA) on TNBC cells with different epithelial character since GA has a wide spectrum of anticancer activity for most cancer types. Methods: We determined the cytotoxic dose of GA incubation of TNBC cells (MDA-MB-231 and BT-20 cells) for 24 h. We performed the MTT test and toluidine blue (TB) staining protocol for TNBC cells. We analyzed E-cadherin, N-cadherin, Bax, and neuroserpin mRNAs in both cells by qPCR. We evaluated apoptosis using DAPI staining and assessed the ROS using the 2',7'-dichlorofluorescin diacetate (DCFH-DA) method. Results: We determined the IC50 concentrations of GA in MDA-MB-231 and BT-20 cells to be 315.8 nM and 441.8 nM, respectively. TB staining showed that BT-20 cells survive at excessive cytotoxic doses of GA, while most of the MDA-MB-231 cells were killed. Also, we found that BT-20 cells are more resistant to GA-induced apoptosis and oxidative stress than the MDA-MB-231 cells. qPCR results showed that GA upregulated neuroserpin, an oxidative stress-relieving factor in the BT-20 cells, but not in the MDA-MB-231 cells. Conclusions: The elevated level of neuroserpin could be a predictive marker to determine the development of resistance to chemotherapeutic agents.
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    Investigation of the protective effects of geraniol on cyclophosphamide-induced hepatotoxicity in rats
    (Natl Inst Science Communication-Niscair, 2025) Canbaz, Halime Tuba; Kalkan, Serpil; Kocabas, Rahim; Sozen, Mehmet Enes; Cuce, Gokhan
    This study aimed to investigate the efficacy of geraniol (Ge) on improving cyclophosphamide (CP)-induced hepatotoxicity in rats. A total of 42 rats in 6 groups, group I (control); group II (CP at 20 mg/kg); group III (CP at 20 mg/kg + Ge at 100 mg/kg); group IV (CP at 20 mg/kg + Ge at 200 mg/kg); group V (Ge at 100 mg/kg); and group VI (Ge at 200 mg/kg), were used. Ge was administered orally via gavage daily for 14 days. Intraperitoneal CP was administered from day 8 to 14. Blood serums were analysed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidant status (TAS), and total oxidant status (TOS) over a 14-day period. Liver sections were stained using hematoxylin and eosin (H&E). NF kappa B expression was assessed using immunohistochemistry. Bax-Bcl immunofluorescence was employed to identify apoptosis, whereas TUNEL was utilised to detect DNA fragmentation. Group III and group IV exhibited significantly decreased histopathological scores, NF kappa B expression, and DNA breaks compared to group II. The OSI and AST levels were significantly reduced in group IV compared to group II. The current investigation indicates that Ge possesses anti-inflammatory and antioxidant effects on CP-induced liver damage.
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    Protective Effects of Selenium against Acrylamide-Induced Hepatotoxicity in Rats
    (Univ Agriculture, Fac Veterinary Science, 2024) Sozen, Mehmet Enes; Savas, Hasan Basri; Cuce, Gokhan
    Acrylamide (ACR) is an organic chemical widely consumed worldwide, depending on the diet. ACR has toxic effects on the liver and other organs due to oxidative damage. The research is aimed to determine the effects of Selenium (Se) against ACR toxicity. 32 Wistar albino male rats were divided into Control, ACR, Se, and ACR+Se groups. After slaughter on the 28 th day, the blood samples taken from the animals were tested for total oxidant status (TOS) and total antioxidant status (TAS) to assess oxidative stress. The liver tissue sections were evaluated for lymphocyte infiltration, hepatocyte degeneration, sinusoid dilatation, and congestion. IL-6, Bax, and Bcl-2 expression were evaluated with immunohistochemistry. While the ACR group's TOS and oxidative stress index (OSI) values were significantly higher than the control group's, there was no significant difference in the ACR+Se group's TOS and OSI values. The ACR group had a considerably higher histopathological score than the other groups. ACR increased IL-6, and Bax levels and decreased Bcl-2 levels compared to the control, Se, and ACR+Se groups. ACR increased oxidative stress significantly caused toxic effects, inflammation, and cell death in the liver. On the other hand, Se oral supplementation may protect against oxidative stress, toxic effects, inflammation, and cell death induced by ACR in the liver.
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    The ameliorative effects of hesperidin in rats developed hepatotoxicity with deltamethrin
    (Mashhad Univ Med Sciences, 2025) Karabekir, Seda Cetinkaya; Sozen, Mehmet Enes; Ayan, Ilknur Cinar; Savas, Hasan Basri; Cuce, Gokhan; Kalkan, Serpil
    Objective(s): Deltamethrin (DLM) is a widely used insecticide in agriculture; however, exposure to it can lead to serious health problems. This study aimed to evaluate the protective effects of hesperidin (HSP), a natural antioxidant, against DLM-induced liver toxicity. Materials and Methods: Thirty-two male Wistar Albino rats (250-300 g, 4 months old) were divided into four groups. The control group received 1 ml of corn oil via oral gavage for 30 days. The DLM group received 1.28 mg/kg DLM in corn oil for 30 days. The DLM+HSP 100 mg/kg and DLM+HSP 300 mg/kg groups received 1.28 mg/kg DLM followed by 100 mg/kg or 300 mg/kg HSP in distilled water, respectively, 30 min after DLM administration for 30 days. Liver tissues were examined histopathologically. Masson's trichrome staining and PCR assessed fibrosis. Caspase 3 and 9 expressions in liver tissues were determined by immunohistochemistry and PCR. Biochemical analyses were conducted on serum samples. Results: HSP supplementation led to a dose-dependent decrease in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. DLM exposure decreased antioxidant capacity, while HSP supplementation increased it dose-dependently. Histopathological evaluations showed increased liver damage in the DLM group, while HSP administration reduced liver toxicity. Masson's trichrome staining and analysis of collagen I (COL1A1) and collagen III (COL3A1) gene expression revealed increased fibrosis in the DLM group, which was attenuated with HSP treatment. Conclusion: The potential prevention of DLM-induced liver toxicity and apoptosis by HSP may be an alternative protective strategy.
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    The effect of tartrazine on angiogenesis and oxidative stress in the chorioallantoic membrane model
    (2025) Savas, Hasan Basri; Sozen, Mehmet Enes; Dinç, Elina
    Tartrazine is commonly preferred as a coloring agent in non-alcoholic beverages, fruit juices, jellies, cereals, and soups. This study aims to investigate the effects of tartrazine exposure on anti-angiogenesis and the oxidant-antioxidant balance. Three different tartrazine dose, a bevacizumab, and an empty pellet used to evaluate anti-angiogenic effects on the chorioallantoic membrane (CAM) model. Fluid samples were collected for measurements of total antioxidant capacity (TAC) and total oxidant status (TOS), from which the oxidative stress index (OSI) was calculated. The control group and 10-6 M tartrazine group had no anti-angiogenic impact, but the bevacizumab group had a strong anti-angiogenic effect. Furthermore, the 10-4 M and 10-5 M tartrazine groups had a weak anti-angiogenic effect. The levels of TOS increase with tartrazine consumption. TAC values were highest in the 10-6 M tartrazine group and lowest in the 10-5 M tartrazine group. Moreover, OSI values have increased in the 10-4 M tartrazine group, 10-5 M tartrazine group, and 10-6 M tartrazine group compared to control group. This study demonstrates that tartrazine exposure leads to dose-dependent increases in oxidative stress and, in parallel, exhibits dose-dependent anti-angiogenic effects. For this reason, it is recommended to be careful when consuming products containing tartrazine.
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    The Oxidative and Anti-Angiogenic Effects of Acrylamide in Chorioallantoic Membrane Model
    (2023) Sozen, Mehmet Enes; Akkaya, Özgür; Savas, Hasan Basri; Karahan, Oguz
    Objective: Acrylamide (ACR) is formed spontaneously during the preparation of carbohydrate-containing foods by exposure to high heat and can be found in large amounts in processed ready-made foods like potato crisps, biscuits, crackers, and bread. ACR is a toxic substance and increases oxidative stress. The aim of the study is to show the effects of ACR exposure at different doses on angiogenesis and oxidant-antioxidant balance in the chorioallantoic membrane (CAM) model. Methods: Two different concentrations of ACR were prepared (10-3 M and 10-4 M). Pellets were placed on the CAM of the embryos. Liquid samples were taken from fertilized chicken eggs before and after the experiment. Anti-angiogenic effects were evaluated through the window that was opened on the eggshell. Results: The 10-4 M ACR group caused anti-angiogenic effects (average score 0.3) which were higher than the control group, but these changes were not statistically significant. The 10-3 M ACR group caused moderate anti-angiogenic effects (average score 0.6). The 10-6 M Bevacizumab group caused powerful anti-angiogenic effects (average score 1). There is a significant increase in total oxidant capacity (TOC) and oxidative stress index (OSI) values in 10-3 M ACR and 10-4 M ACR groups, compared to the control group. Although there was a numerical increase in TOC and OSI values in 10-3 M ACR group compared to 10-4 M ACR group, this increase was not statistically significant. Conclusion: This study is the first to investigate the anti-angiogenic effects of ACR and is one of the first to investigate oxidative stress in the CAM model. ACR exposure increased oxidative stress in the CAM model and showed a dose-dependent anti-angiogenic effect.