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Item Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion(MDPI, 2022-01-01) Genc, Sidika; Pennisi, Manuela; Yeni, Yesim; Yildirim, Serkan; Gattuso, Giuseppe; Altinoz, Meric A.; Taghizadehghalehjoughi, Ali; Bolat, Ismail; Tsatsakis, Aristidis; Hacimuftuoglu, Ahmet; Falzone, LucaHigh-grade gliomas are the most fatal brain tumors. Grade 4 gliomas are called glioblastoma multiforme (GBM), which are associated with the poorest survival and a 5-year survival rate of less than 4\%. Many patients with GBM developed concomitant cognitive dysfunctions and epilepsy. Although the cognitive decline is well defined in glioblastomas, the neurotoxic factors underlying this pathology are not well understood in GBM patients. In this study, we aimed to investigate whether GBM-derived exosomes play a role in neuronal toxicity. For this purpose, exosomes obtained from T98G and U373 GBM cells were applied to primary neuron culture at different concentrations. Subsequently, MTT, LDH, GSH, TAS, and TOS tests were performed. Both GBM-derived exosomes induced a dose-dependent and statistically significant increase of LDH release in cerebellar neurons. MTT assay revealed as both T98G and U373 GBM-derived exosomes induced dose-dependent neurotoxic effects in cerebellar neurons. To the best of our knowledge, this study is the first study demonstrating the toxic potential of GBM-derived exosomes to primary neurons, which may explain the peritumoral edema and cognitive decline in GBM patients.Item Oxidative Stress and Marine Carotenoids: Application by Using Nanoformulations(MDPI, 2020-01-01) Genc, Yasin; Bardakci, Hilal; Yucel, Cigdem; Karatoprak, Gokce Seker; Akkol, Esra Kupeli; Barak, Timur Hakan; Sobarzo-Sanchez, EduardoCarotenoids are natural fat-soluble pigments synthesized by plants, algae, fungi and microorganisms. They are responsible for the coloration of different photosynthetic organisms. Although they play a role in photosynthesis, they are also present in non-photosynthetic plant tissues, fungi, and bacteria. These metabolites have mainly been used in food, cosmetics, and the pharmaceutical industry. In addition to their utilization as pigmentation, they have significant therapeutically applications, such as improving immune system and preventing neurodegenerative diseases. Primarily, they have attracted attention due to their antioxidant activity. Several statistical investigations indicated an association between the use of carotenoids in diets and a decreased incidence of cancer types, suggesting the antioxidant properties of these compounds as an important factor in the scope of the studies against oxidative stress. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. Marine carotenoids (astaxanthin, fucoxanthin, beta-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. Numerous of bioactive compounds such as marine carotenoids have low stability, are poorly absorbed, and own very limited bioavailability. The new technique is nanoencapsulation, which can be used to preserve marine carotenoids and their original properties during processing, storage, improve their physiochemical properties and increase their health-promoting effects. This review aims to describe the role of marine carotenoids, their potential applications and different types of advanced nanoformulations preventing and treating oxidative stress related disorders.Item Protective effect of pomegranate juice on retinal oxidative stress in streptozotocin-induced diabetic rats(IJO PRESS, 2017-01-01) Tugcu, Betul; Nacaroglu, Senay Asik; Gedikbasi, Asuman; Uhri, Mehmet; Acar, Nur; Ozdemir, HakanAIM: To investigate the effect of pomegranate juice (PJ) intake on overall oxidation status in retinas of diabetic rats. METHODS: Twenty-seven rats were divided into four groups as control (CO), diabetic (DM), control treated with PJ (CO-PJ), and diabetic treated with PJ (DM-PJ). The retina tissues were used to determine 8-hydroxy2 `-deoxyguanosine (8OHdG), malondialdehyde (MDA), reduced glutathione (GSH) levels, and the enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). RESULTS: The levels of 8OHdG and MDA were significantly increased in the retina of DM group compared to CO group (P= 0.001, P< 0.001 respectively). Both 8OHdG and MDA levels were decreased in PJ-DM group compared to DM group (P= 0.004, P< 0.001 respectively). The activities of antioxidant enzymes GSH, SOD, and GDH-Px were significantly decreased in the retina of DM group compared to CO group (P= 0.01). GSH and GSH-Px activities were higher in PJ-DM group compared with DM group (P= 0.010, P= 0.042, respectively) but SOD activity was not statistically different (P= 0.938). CONCLUSION: PJ intake is found to be effective in decreasing oxidative end products, and in increasing the activities of antioxidant enzymes in diabetic retinas of rats, which suggests it may be effective against oxidative stress in diabetic retinas.Item Cellular stress responses of long-lived and cancer-resistant naked mole-rats(WALTER DE GRUYTER GMBH, 2021-01-01) Bozaykut, PerinurObjectives: Some organisms are long-lived and naturally resistant to cancer such as naked mole-rats (NMRs). Studies have shown that these animals can better tolerate stress due to mechanisms, such as upregulation of antioxidant pathways and improved proteostasis. In the present study, we aimed to analyze the tolerance against stress and the cellular mechanisms related to the stress response in NMR cells comparative to mouse cells. Materials and methods: NMR and mouse fibroblasts were exposed to cellular stresses including H2O2 and/or NaNO3 and the viability of the cells were analyzed. In addition messanger RNA (mRNA) expression of antioxidant transcription factor Nuclear factor erythroid-derived 2-like 2 (Nrf2) and its target gene NAD(P)H quinone dehydrogenase 1 (NQO1) were determined by qRT-PCR and comprehensive analysis of stress-related gene expression was performed by RNA-Sequencing in fibroblasts and induced pluripotent stem cells (iPSC). Results: Surprisingly, NMR fibroblasts were found to be more sensitive than mouse cells to H2O2 and NaNO3. Furthermore, it was shown that fibroblasts and iPSCs mainly aren't identical in the expression pattern of cellular defense signaling and several factors are mainly downregulated in NMR iPSCs. Conclusions: Collectively, the data gained from the present study help to improve the understanding of evolved mechanisms that contribute to stress resistance, aging and cancer.Item Morphological evaluation of the effects of exercise on high-fat-diet-induced liver damage in rats(AVES, 2020-01-01) Elmas, Merve Acikel; Atay, Nilsu; Ozakpinar, Ozlem Bingol; Arbak, Serap; Kolgazi, Meltem; Sener, Goksel; Ercan, FerihaBackground/Aims: This study was aimed to investigate the protective effects of swimming on nonalcoholic fatty liver disease associated with high-fat-diet-induced obesity using microscopic and biochemical parameters. Materials and Methods: Sprague-Dawley male rats were fed either standard chow (STD groupItem The effect of 1,25-dihydroxyvitamin D3 on liver damage, oxidative stress, and advanced glycation end products in experimental nonalcoholic- and alcoholic- fatty liver disease(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2021-01-01) Bingul, Ilknur; Aydin, A. Fatih; Kucukgergin, Canan; Dogan-Ekici, Isin; Dogru-Abbasoglu, Semra; Uysal, MujdatBackground/aim: Oxidative stress and advanced glycation end products (AGEs) formation are proposed as effective mechanisms in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). 1,25(OH)(2)D-3 was proposed to have antioxidant, antiinflammatory and antiglycation properties. In this study, the effect of 1,25(OH)(2)D-3 treatment on oxidative stress parameters and AGEs levels together with hepatic histopathology was investigated in high fructose (HFr) or ethanol (EtOH)-treated rats. Materials and methods: Rats were treated with fructose (30\%) or ethanol (5-20\%) in drinking water with and without 1,25(OH)(2)D-3 treatment (5 mu g/kg two times a week) for 8 weeks. Insulin resistance (IR), oxidative stress parameters, AGEs, triglyceride (TG), and hydroxyproline (Hyp) levels together with histopathology were investigated in the liver. Results: 1,25(OH)(2)D-3 decreased hepatic reactive oxygen species, lipid and protein oxidation products together with histopathological improvements in HFr- and EtOH-treated rats. 1,25(OH)(2)D-3 treatment was observed to decrease significantly serum and hepatic AGEs in HFr group, and hepatic AGEs in EtOH group. Conclusion: Our results clearly show that 1,25(OH)(2)D-3 treatment may be useful in the alleviation of hepatic lesions by decreasing glycooxidant stress in both NAFLD and ALD models created by HFr- and EtOH-treated rats, respectively.Item Obstructive Sleep Apnea and Cancer(GALENOS PUBL HOUSE, 2016-01-01) Demir, Ceyda Erel KirisogluObstructive sleep apnea (OSA) is a common disorder which is associated with increased morbidity and mortality. There is growing evidence that patients with OSA have higher incidence of cancer, accelerated progression and cancer mortality. Intermittent hypoxia, oxidative stress and sleep fragmentation are hold responsible for cancer development.