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Yayın Comparison of oxidative stress biomarkers in renal tissues of D-galactose induced, naturally aged and young rats(Springer, 2012) Aydın, Şeval; Yanar, Karolin; Atukeren, Pınar; Dalo, Enis; Sitar, Mustafa Erinç; Uslu, Ezel; Caf, Nazlı; Çakatay, UfukAgeing of kidneys is a clinical health issue of the society. Age-related renal insufficiency has important implications due to impaired redox homeostasis. We examined protein, DNA and lipid oxidation biomarkers as well as protein-bound sialic acid (SA) in the kidney tissues of D-galactose induced ageing rats, naturally aged rats and their corresponding young control group. Intraperitoneal injection of D-galactose (60 mg/kg/day) for 6 weeks to young male Sprague–Dawley rats (20-week-old) was used to establish mimetic ageing model. In this study, we investigated the levels of protein carbonyl groups (PCO), various thiol fractions such as total thiol groups (T-SH), protein (P-SH) and non-protein thiol groups (NP-SH), lipid oxidation parameters such as lipid hydroperoxides (LHP) and malondialdehyde (MDA), SA and 8-hydroxy-2?deoxyguanosine (8-OHdG) parameters for comparison of naturally aged, induced aged and young rats. In D-galactose induced aged group, PCO, LHP, MDA, and 8-OHdG concentrations were significantly higher than young control group, whereas T-SH, P-SH levels were significantly lower than the young rats. In addition, NP-SH and SA concentrations were similar between the mimetic ageing and young control groups. In naturally ageing rats, PCO and MDA levels were significantly higher, whereas T-SH, P-SH, NP-SH concentrations were low compared to young controls. On the other hand, SA and 8-OHdG levels were not different between the naturally ageing group and the young control group. Our results demonstrated that the rats in the mimetic ageing group, have significant similarities with the naturally aged rats in terms of impaired redox homeostasis and can be used as a reliable animal model for renal ageing.Yayın A comprehensive study of myocardial redox homeostasis in naturally and mimetically aged rats(National Library of Medicine, 2014) Cebe, Tamer; Yanar, Karolin; Atukeren, Pınar; Ozan, Tuna; Kuruç, Aylin Irmak; Kunbaz, Ahmad; Sitar, Mustafa Erinç; Mengi, Murat; Aydın, Mehmet Şerif; Eşrefoğlu, Mukaddes; Aydın, Şeval; Çakatay, UfukAge-related myocardial dysfunction has important implications with impaired redox homeostasis. Current study focused on investigation of redox homeostasis and histopathological changes in the myocardium of mimetically (MA), naturally aged (NA), and young control (YC) rats. Chronic d-galactose administration to young male Wistar rats (5 months old) was used to set up experimental aging models. We investigated 16 different oxidative damage biomarkers which have evaluated redox homeostasis of cellular macromolecules such as protein, lipid, and DNA. As a protein oxidation biomarker, advanced oxidation end products, protein carbonyl groups, protein-bound advanced glycation end products, dityrosine, kynurenine, and N-formylkynurenine concentrations in MA and NA rats were found to be significantly higher compared to those in YC rats. On the other hand, the levels of protein thiol groups were not significantly different between groups, whereas lipid peroxidation biomarkers such as conjugated diens, lipid hydroperoxides, and malondialdehyde in MA and NA rats were found to be significantly higher in comparison to those in YCs. For the assessment of oxidative DNA damage, we analyzed eight hydroxy-5?-deoxyguanosine concentrations of MA and NA groups which were higher than YCs. As an antioxidant status in the MA and NA groups, Cu–Zn superoxide dismutase, ferric reducing antioxidant power, and total thiol levels were lower than those in the YCs. Only nonprotein thiol levels were not significantly different. We also observed similar histopathological changes in MA and NA rats. We concluded that the mimetic aging model could be considered as a reliable experimental model for myocardial senescence.Yayın Crucial roles of systemic and tissue lipid peroxidation levels and anti-oxidant defences following contrast agent application(National Library of Medicine, 2016) Sitar, Güngör; Küçük, Mehmet; Sitar, Mustafa Erinç; Yaşar, Özgür; Aydın, Şeval; Yanar, Karolin; Çakatay, Ufuk; Büyükpınarbaşılı, NurBackground: One of the most important side effects of contrast pharmaceutical agents, which are used very common in routine radiology practice, is contrast induced nephropathy. Even ischemia, oxidative stress and osmolality related cytotoxic effects are considered, the molecular mechanisms underlying this pathology have not been identified completely yet. Objectives: The aim of the current study was to reveal the role of oxidative stress and antioxidant enzymatic defence mechanisms in the aetiopathogenesis of contrast-induced nephropathy. We also studied possible alleviating effects of N-acetylcysteine (NAC), a potent antioxidant, to obtain extra information regarding the molecular mechanisms underlying this pathology. Materials and Methods: This is an clinical-experimental study, This study was conducted of Istanbul/Turkey between September 15, 2012 and April 15, 2013. Three groups of male rats were randomly set up as a control group (C), a 100 mg/kg intraperitoneal NAC + 7 mL/kg contrast agent group (N + CIN) and a 7 mL/kg intraperitoneal contrast agent group (CIN). They were placed in individual metabolic cages 48 hours after agent administration to obtain 24-hour urine samples. Renal function tests (albumin, urea, creatinine, total protein) were conducted, oxidative stress parameters (Cu, Zn superoxide dismutase activity - Cu, Zn-SOD; advanced oxidation protein products - AOPP; protein carbonyls - PCO; total thiol groups - T-SH; and lipid hydroperoxides -LHP) were measured and tissues were analysed histopathologically. Results: Compared with the control group, groups CIN and N + CIN had significantly higher urea and LHP levels (P < 0.05 and P < 0.001, respectively) and significantly lower Cu, Zn-SOD activity and creatinine clearance (P < 0.05). There was no statistically significant difference between the groups in PCO or AOPP levels despite differences in descriptive statistics. Conclusions: Contrast-agent-induced nephropathic changes are more closely related to the magnitude of lipid peroxidation than protein oxidation.Yayın Current aspects of ageing theories and classification according to mechanisms(Turkish Geriatrics Society, 2013) Sitar, Mustafa Erinç; Yanar, Karolin; Aydın, Şeval; Çakatay, UfukAttempts to define ageing, explain theories and classify them have always been an important issue for biogerontologists. Oxidative stress, telomeres, genetics, hormonal changes, immunity and damage accumulation over threshold values are all common theories that have been studied and modified over a long period of time. Verifications of these theories may lead to enlightenment about molecular mechanisms, and these can give rise to new research to reverse or slow age related pathological changes and increase average life span. Nowadays, an increased ratio of “successful ageing” or “healthier ageing” is a big aim for the whole society. Achieving this purpose also depends on research which studies molecular mechanisms and routine laboratory markers of ageing.Yayın Galactose-induced aging model in rat testicular tissue(College of Physicians & Surgeons, 2018) Aydın, Şeval; Yanar, Karolin; Şimşek, Bahadır; Cebe, Tamer; Sitar, Mustafa Erinç; Belce, Ahmet; Çakatay, UfukObjective: To examine whether the D-galactose induced aging model is an appropriate model for further aging research. Study Design: Experimental study. Place and Duration of Study: Aziz Sancar Institute of Experimental Medicine, Istanbul University, Turkey, June 2015- June 2017. Methodology: The study comprises 3 groups of rats. Group I is young control (YC) 5-month-old rats. Group II is 5-monthold rats, which were mimetically aged (MA) for 6 weeks via intraperitoneal D-galactose (60 mg/kg body weight/day, 0.5 mL) administration. Group III is naturally aged (NA) 24-month-old rats. Group I and III received intraperitoneal saline (0.9% 0.5 mL) for 6 weeks as vehicle. Group I and Group II received injections at 21 weeks age and Group III rats 6 weeks before 24 months age. Tissues were harvested when rats became 6.5-month-old (Group I and Group II) and 24-month-old (Group III). Quantitative biochemical analyses of proteins, lipids, DNA biomarkers and Cu, Zn-SOD were conducted. Statistical analysis of the data was conducted using ANOVA, followed by post-hoc Bonferroni test. Results: Higher magnitude of oxidative damage and diminished antioxidant defence capacity were found in both mimetically aged and naturally aged testicular tissues. It is observed that D-galactose aging model group shares significant similarities in terms of impaired redox homeostasis with the naturally aged rats. Conclusion: D-galactose induced testicular aging model successfully mimics aging process. Therefore, D-galactose induced aging model may be used as an accelerated aging model to study the age related alterations and interventions.Yayın Human serum albumin and its relation with oxidative stress(Clinical Laboratory Publications GmbH, 2013) Sitar, Mustafa Erinç; Aydın, Şeval; Çakatay, UfukHuman serum albumin, a negative acute phase reactant and marker of nutritive status, presents at high concentrations in plasma. Albumin has always been used in many clinical states especially to improve circulatory failure. It has been showed that albumin is involved in many bioactive functions such as regulation of plasma osmotic pressure, binding and transport of various endogenous or exogenous compounds, and finally extracellular antioxidant defenses. Molecules like transferrin, caeruloplasmin, haptoglobin, uric acid, bilirubin, alpha-tocopherol, glucose, and albumin constitute extracellular antioxidant defenses in blood plasma but albumin is the most potent one. Most of the antioxidant properties of albumin can be attributed to its unique biochemical structure. The protein possesses antioxidant properties such as binding copper tightly and iron weakly, scavenging free radicals, e.g., hypochlorous acid (HOCl) and Peroxynitrite (ONOOH) and providing thiol group (-SH). Whether it is chronic or acute, during many pathological conditions, biomarkers of oxidative protein damage increase and this observation continues with considerable oxidation of human serum albumin. There is an important necessity to specify its interactions with Reactive Oxygen Species. Generally, it may lower the availability of pro-oxidants and be preferentially oxidized to protect other macromolecules but all these findings make it necessary that researchers give a more detailed explanation of albumin and its relations with oxidative stress.Yayın Hyperoxic oxidative stress during abdominal surgery: a randomized trial(Springer, 2016) Köksal, Güniz M.; Dikmen, Yalım; Erbabacan, Emre; Aydın, Şeval; Çakatay, Ufuk; Sitar, Mustafa Erinç; Altındaş, FatişPurpose The hypothesis of our study is that during anesthesia, administration of 80 % oxygen concentration increases oxidative stress more than 40 % oxygen. Methods Forty ASA I-II patients were included in a randomized, single-blind study. Expiratory tidal volumes (ETV) were measured before induction and after extubation. After ventilation with 0.8 FiO2 and intubation, mini-bronchoalveolar lavage (mini-BAL), arterial blood gas (ABG), and blood samples were taken. Patients were randomly assigned to receive 0.8 (group I) or 0.4 (group II) FiO2 during management. Before extubation, mini-BAL, ABG, blood samples were taken. PaO2/FiO2, lactate, malondialdehyde (MDA), protein carbonyl (PCO), superoxide dismutase (SOD), total sulfhydryl (T-SH), non-protein sulfhydryl (NPSH), and protein sulfhydryl (PSH) were measured. In both groups, mean arterial pressure and heart rate values were recorded with 30-min intervals. Results ETV values were higher in group II after extubation. PaO2/FiO2 values were higher in group II after extubation compared to group I. In both groups, plasma PCO, SOD, and T-SH levels increased significantly before extubation, whereas the increase in MDA was not significant between groups. Plasma PCO, T-SH, and lactate levels were higher in group I, and plasma SOD, and PSH were higher in group I before extubation. In both groups, MDA, SOD, T-SH, and NPSH levels in mini-BAL increased significantly before extubation. Between-group comparisons, PCO, T-SH, PSH, and NPSH were significantly higher in the BAL samples of group II, and MDA levels were higher in group I. Conclusions We found that 80 % FiO2 decreased ETV and PaO2/FiO2 and increased lactate levels and oxidative stress more, inhibiting antioxidant response compared to 40 % FiO2.Yayın Oxidation scrutiny in persuaded aging and chronological aging at systemic redox homeostasis level(Elsevier, 2014) Cebe, Tamer; Atukeren, Pınar; Yanar, Karolin; Kuruç, Aylin Irmak; Ozan, Tuna; Kunbaz, Ahmad; Sitar, Mustafa Erinç; Mirmaroufizibandeh, Reza; Aydın, Şeval; Çakatay, UfukBackground The effect of the natural aging process on systemic redox homeostasis is previously documented. However, none of the studies specify the effect of experimental aging on systemic redox homeostasis. The purpose of this study is to clarify the ambiguity raised in preliminary reports as to mimetic aging dependency of the type and magnitude of oxidative damage on constituents of plasma. Methods In the current study, we investigated the interrelationship among various groups of the systemic oxidative damage markers such as protein oxidation products (protein carbonyl groups, protein hydroperoxides, advanced oxidation protein products, protein thiol groups), lipid peroxidation products (malondialdehyde, lipid hydroperoxides, conjugated dienes), glycoxidation adducts (advanced glycation end products), and antioxidant capacity (ferric reducing/antioxidant power, Cu,Zn-superoxide dismutase, total thiol, non-protein thiol). All these markers were measured in plasma of mimetically aged (MA) rats (5-month-old rats subjected to d-galactose-induced experimental aging), naturally aged (NA) rats (24-month-old), and their corresponding young controls (YC) (5 months old). Results and conclusions Our current results show that systemic oxidation markers of the MA group share significant similarities in terms of impaired redox homeostasis with the NA rats and may be considered as a reliable experimental aging model for intravascular aging. Additional methodological studies including d-galactose dosage and application time are warranted to clarify the potential involvement of all these systemic redox variations as mechanistic factors in the development of mimetic aging related intravascular deterioration. Reversing or preventing systemic oxidative damage in experimental and natural aging should therefore be considered the primary target for the development of effective therapeutic strategies to prevent or treat age-related vascular disorders.Yayın Oxidative damage parameters in renal tissues of aged and young rats based on gender(National Library of Medicine, 2013) Uzun, Duygu; Güntaş Korkmaz, Gülcan; Sitar, Mustafa Erinç; Cebe, Tamer; Yanar, Karolin; Çakatay, Ufuk; Aydın, ŞevalPurpose Aging is characterized by a gradual functional decrease of all systems including the kidneys. Growing evidence links altered lipid protein redox-homeostasis with renal dysfunction. The effect of sexual dimorphism on the lipid protein redox-homeostasis mechanisms in the aging kidney is obscure. In the current study, we aimed to investigate redox homeostasis as it related to sexual dimorphism on protein oxidation and lipid peroxidation parameters, as protein carbonyl (PCO), total thiol (T-SH), advanced oxidation protein products (AOPP), malondialdehyde, glutathione (GSH), and superoxide dismutase (SOD) activity, as potential aging biomarkers, which may contribute to an analysis of the free radical theory of aging. Materials and methods The study was carried out with 16 naturally aged rats (24 months old; eight males and eight females) and their corresponding young rat groups as controls (6 months old; eight males and eight females). All of the aforementioned parameters (PCO, T-SH, AOPP, MDA, GSH, SOD) were measured manually instead of automated devices or ELISA kits. Results PCO, AOPP, and malondialdehyde levels in aged rats were significantly higher in the older rat group than in the younger rat group, whereas SOD activities were significantly lower in old rats. T-SH levels were not significantly different in male groups; however, T-SH levels were lower in the aged female group than in the young female control group. In addition, GSH levels were significantly different between the aged rat group and the corresponding young control group for both genders. Conclusion With respect to PCO and AOPP, impaired redox homeostasis is substantially more prominent in males than females. The decrease of G-SH levels in male groups could be attributed to stabilizing the redox status of protein thiol groups by the depletion of the GSH groups. Considering the results, the renal tissue proteins and lipids in different genders may have different susceptibilities to oxidative damage.
