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Öğe Calcium Fructoborate Prevents Skin Cancer Development in Balb-c Mice(Humana Press Inc, 2020) Kisacam, Mehmet Ali; Kocamuftuoglu, Gonca Ozan; Ozan, Ibrahim Enver; Yaman, Mehmet; Ozan, Sema TemizerTumor microenvironment, genetic, and non-genetic factors are responsible for the atypical metabolic feature of cancer cells. Aberrant activity of PI3K/Akt pathway, increased glycolytic flux, and decreased intracellular pH gradient are the leading causes of this feature. Calcium Fructoborate (CaFB), a sugar-borate ester, has major benefits for human health. The aim of this study was to explore the implication of CaFB on experimentally induced skin cancer in vivo. According to the treatment, 92 female Balb-c mice are divided into six groups: control, CaFB (3 mg/kg/day), 7,12-Dimethylbenz(a)anthracene (DMBA)+12-O-tetradecanoylphorbol-13-acetate (TPA) (97.5 nmol DMBA, 6.5 nmol TPA), T1: CaFB+DMBA+TPA (3 mg/kg/day CaFB together with DMBA), T2: DMBA+CaFB+TPA (3 mg/kg/day CaFB together with TPA), T3: DMBA+TPA+CaFB (3 mg/kg/day CaFB after tumor formation). Topical DMBA and TPA application resulted in a significant increase in the protein levels, immunoreactivity, and mRNA expression of HRAS, HIF1 alpha, Akt, and PTEN (p< 0.05). Moreover, an increase in the number of TUNEL-positive cells was observed in DMBA-TPA group compared with the control group (p< 0.05). CaFB application reduced the protein levels, immunoreactivity, and mRNA expressions of HRAS, HIF1 alpha, Akt, and PTEN and also decreased the number of TUNEL-positive cells. Recent evidence obtained from our study validated that CaFB treatment may have skin cancer-preventing effect.Öğe Calcium Fructoborate Prevents Skin Cancer Development in Balb-c Mice: Next Part, Reverse Inflammation, and Metabolic Alteration(Springernature, 2021) Kisacam, Mehmet Ali; Kocamuftuoglu, Gonca Ozan; Ozan, Ibrahim Enver; Yaman, Mehmet; Ozan, SemaTemizerMetabolic alterations and inflammation are regarded as hallmarks of cancer. Glycolytic flux and intermediate accumulation lead to the production of building blocks and NADPH which is important in protecting the cell from oxidative damage. Inflammation causes the release of mediators responsible for regulating molecular mechanism affecting metabolic pathways. CaFB due to its cis-diol-rich feature may have the potential to interact with molecules taking part in cancer development. This study was aimed to investigate the effects of CaFB on metabolic alterations and inflammation in 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin cancer. For this purpose, 92 Balb-c mice were distributed into 6 groups as control, CaFB, DMBA/TPA (D-T), treatment 1 (T1), 2 (T2), and 3(T3). Apart from control and CaFB in other groups, tumors initiated with 97.5-nmol DMBA and 6.5-nmol TPA. Treatment groups received 3 mg/kg/day CaFB with DMBA (T1), with TPA (T2), and after tumor formation (T3). In the D-T group, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, 6-phosphogluconate dehydrogenase (PGD), glutathione (GSH), interleukin 6 (IL-6), (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) levels increased (p < 0.001) while malondialdehyde (MDA) levels decreased (p < 0.001) compared with that in control. CaFB application ameliorated DMBA-TPA effect according to the distribution time. It is noteworthy to consider CaFB as a potential preventive agent in skin cancer development.Öğe The evaluation of early stage oxidative status in streptozotocin induced diabetes in rats(Taylor & Francis Ltd, 2022) Kisacam, Mehmet Ali; Kocamuftuoglu, Gonca Ozan; Ufat, Hakan; Ozan, Sema TemizerEarly-stage diabetes can be defined as the stages before absolute insulin deficiency in patients. In this study, the early stage oxidative effect of streptozotocin(STZ) induced diabetes mellitus was evaluated. 28 male adult Sprague-Dawley rats were divided into four groups; control group and 7th, 14th, 21st days diabetic groups. Diabetic groups received single 65 mg/kg STZ injection intraperitoneally. Rats were decapitated at 7th, 14th and 21st days, liver tissues were taken. Nitric oxide(NO), malondialdehyde(MDA) levels and catalase, arginase activities were measured. MDA and NO levels were increased (respectivelyp < .001 andp < .01), mainly 14 and 21 days after STZ administration; moreover, while liver catalase activity was progressively decreased (p < .001), oppositely arginase was increased in the same time period (p < .01). Results show that MDA and nitric oxide together with catalase and arginase switch at an early stage of diabetes and they may contribute to subsequent complications related to diabetes via increased oxidative damage.Öğe The evaluation of the therapeutic potential of hesperetin on diethylnitrosamine and phenobarbital induced liver injury in rats(Ankara Univ, 2022) Kisacam, Mehmet Ali; Kocamuftuoglu, Gonca Ozan; Tektemur, Nalan Kaya; Ozan, Penbe Sema TemizerNitrite and amine reactions can occur rapidly and produce nitrosamines, in-vivo. Diethylnitrosamine (DEN) and phenobarbital (PB) are readily inducing liver injury and hesperetin (HES), as a flavonoid found in citrus fruits, have the potential to compensate for their harmful effects. In this study, the therapeutic effects of HES were evaluated in DEN and PB mediated liver defect. Adult male Sprague-Dawley rats were split into 5 groups (n=10): Control, DEN, DEN+PB, HES, and DEN+PB+HES. 150 mg/kg DEN was applied intraperitoneally to DEN groups. Fifteen days after the DEN application 500ppm of PB was given in drinking water. HES were administered at 50 mg/kg dose orally for 8 weeks. Blood and liver malondialdehyde (MDA), glutathione (GSH) levels, and catalase (CAT), superoxide dismutase (SOD) activities were measured spectrophotometrically. Moreover, histologic examination of liver sections and apoptosis were determined with hematoxylin-eosin and TUNEL methods, respectively. DEN-PB application was found to increase blood and liver MDA levels and liver CAT activity, oppositely, decreased blood and liver SOD activity, GSH levels, and blood CAT activity. HES was found to have a positive impact on oxidative stress parameters by decreasing liver and blood MDA activity, increasing blood CAT and SOD activity together with liver GSH levels and SOD activity. Whereas DEN and PB application increased all histopathological findings and TUNEL positive cells, HES administration decreased these findings which might be important for the protection of liver cell structure from cell damage. These results suggest that HES administration could be an alternative therapeutic approach to liver damage.Öğe Oleuropein reduces the oxidative effects of tobacco smoke in rats’ liver and kidney(Springer Science and Business Media Deutschland GmbH, 2022) Kocamuftuoglu, Gonca Ozan; Kisacam, Mehmet Ali; Tektemur, Nalan Kaya; Yilmaz, Osman Fatih; Ozan, Ibrahim Enver; Ozan, Sema Temizer; Bircan, Filiz SezenTobacco smoke contains free radicals, which can potentiate the initiation and promotion of oxidative damage. Nitric oxide (NO) is easily converted into nitric oxide radicals found in tobacco smoke. Nitric oxide synthase and arginase, which might participate in oxidative stress, are two rival enzymes using the same substrate. Oleuropein (OLE) is the main phenolic compound found in olive leaves and has important antioxidant properties. In this study, potential protective effects of OLE on tobacco, smoke-exposed rats were evaluated. Eighteen male Sprague Dawley rats were divided into 3 groups: Control, Tobacco smoke, Tobacco smoke + OLE. The rats in tobacco smoke and tobacco smoke + OLE were exposed to tobacco smoke in a glass chamber for 1 h every other day for 12 weeks. Tobacco smoke + OLE were received 10 mg/kg OLE for the last 4 weeks by oral gavage. After 12 weeks, rats were decapitated; kidney and liver tissues were taken. Malondialdehyde (MDA), glutathione (GSH), NO levels together with catalase (CAT) and arginase activity were measured. MDA levels increased in the liver and kidney, while CAT activity and GSH levels decreased in tobacco smoke group. OLE administration decreased MDA levels while increasing CAT activity and GSH levels. NO levels increased in the liver following tobacco smoke, yet, OLE did not change NO significantly. Furthermore, kidney NO levels increased following tobacco smoke and OLE decreased this level. Tobacco smoke did not change kidney arginase levels while OLE decreased this activity. Our results showed that OLE could be beneficial in reducing the negative impact of tobacco smoke on both the liver and kidney. © 2022, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.
