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    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.
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    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.
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    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.
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    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.
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    Probiotics ameliorates LPS induced neuroinflammation injury on A beta 1-42, APP, gamma-beta secretase and BDNF levels in maternal gut microbiota and fetal neurodevelopment processes
    (Springer/Plenum Publishers, 2022) Kar, Fatih; Hacıoğlu, Ceyhan; Kar, Ezgi; Donmez, Dilek Burukoglu; Kanbak, Güngör
    The gut microbiota influences brain development and functioning through the gut-brain axis. This is first study regulate maternal gut microbiota and fetal neurodevelopment processes by using probiotics such as Bifidobacterium bifidum (BIF) and Lactobacillus salivarius (LAC) in the prenatal period. In this study, Wistar Albino female rats were divided into five groups; Control, lipopolysaccharide (LPS, 100 mu g/kg), LPS + LAC, LPS + BIF and LPS + LAC + BIF (4 x 10(9) ml CFU). Maternal rats were given probiotics for 21 days. Inflammation was induced by lipopolysaccharide (LPS), on the 17th day of pregnancy. After birth, the brain tissues of the maternal and neonatal rats were removed and their blood was collected. Fecal calprotectin levels of pregnant rats were measured as an important biomarker in determining intestinal flora disruption. Calprotectin levels were high in LPS group (p < 0.05). A beta 1-42, APP, gamma secretase and beta- secretase levels were higher in both maternal and neonatal LPS groups (p < 0.05). These levels were statistically decreased in the probiotic groups compared to the LPS group, as demonstrated in both biochemical and histological analyzes (p < 0.05). While BDNF mRNA expression decreased in LPS groups, APP level increased in the same group. The difference between groups in mRNA expressions in the neonatal brain tissues was similar to maternal brain tissues. What's more, BDNF/actin and APP/actin rates were proven by western blot and the damage caused by neuroinflammation in the brain tissue and the preservation of the intestinal microbiota were visualized histopathologically on the morphological structures in all groups. It will shed light on new therapeutic strategies for the impact of the use of probiotics on the neurodevelopmental processes of the neonatal against LPS-induced inflammatory responses and impaired gut microbiota in the prenatal period.