Mustafa Erinç Sitar

Oxidation scrutiny in persuaded aging and chronological aging at systemic redox homeostasis level

BACKGROUND 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) (5months 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.

Oxidative damage parameters in renal tissues of aged and young rats based on gender

Purpose 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.

Increased Protein Oxidation and Loss of Protein-Bound Sialic Acid in Hepatic Tissues of D-galactose Induced Aged Rats

A redox basis of the increased oxidative protein damage and free radical-mediated desialylation have not been fully elucidated in aging. It is well known that the incidence of several liver diseases increase with age. This original research focuses on protein oxidation mechanisms and protein-bound sialic acid levels in liver tissue of the mimetic aging rats. Injection of D-galactose (60 mg/kg/day) for six weeks to male Sprague-Dawley rats (20-week-old) used to establish mimetic aging model. We investigated the tissue levels of various protein oxidation markers such as protein carbonyl groups, suitable advanced oxidation protein products and protein thiol groups. Our study also covered protein-bound sialic acid in liver tissue of D-galactose-induced aging rats. PCO (Protein Carbonyl Groups), P-OOH (Protein Hydroperoxides) and AOPP (Advanced Oxidation Protein Products) levels in aging rats were significantly higher compared to young control groups. On the other hand, P-SH (Protein Thiol Groups) levels were not found to be different between two groups. SA (Sialic Acid) levels in D-galactose-induced aging rats were significantly lower compared to control groups. Our results demonstrated greater susceptibility to hepatic oxidative protein damage and desialylation of hepatocellular proteins in Dgalactose- induced aging rats. These molecular mechanisms may be operative in the many age-related liver diseases, which are pertinent to increased oxidative stress and altered redox homeostasis.

Crucial Roles of Systemic and Tissue Lipid Peroxidation Levels and Anti-Oxidant Defences Following Contrast Agent Application

Background 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.

Galactose-induced Aging Model In Rat Testicular Tissue

OBJECTIVE 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-month- old 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.