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    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 Temizer
    Tumor 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.
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    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, SemaTemizer
    Metabolic 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.
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    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 Sezen
    Tobacco 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.