Karolin Yanar

Gender-dependent variations in systemic biomarkers of oxidative protein, DNA, and lipid damage in aged rats

Introduction. The effect of aging on plasma-protein, lipid and DNA oxidation is well documented. However, none of the studies specify the effect of gender. The purpose of this study is to clarify the ambiguity raised in preliminary reports as to gender dependency of oxidative damage in plasma. Methods. In the current study, we investigated the relation between 8-hydroxy-2′-deoxyguanosine levels (8-OHdG), which is a measure of DNA oxidation and protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH), and advanced oxidation protein products (AOPP). Our study also covered other oxidative stress parameters, such as lipid hydroperoxides (LHP), malondialdehyde (MDA), erythrocyte glutathione (GSH), superoxide dismutase (Cu-Zn SOD) and the catalase (CAT) activity in plasma of the male and female aged rats. Results. 8-OHdG and MDA levels in male rats were significantly higher than those in the female group (p < 0.01 for both parameters). T-SH levels were found to be higher in female rats than in the male (p < 0.05). Plasma Cu-Zn SOD activities of male rats were significantly higher compared with those of the female rats (p < 0.05). On the other hand, PCO, AOPP, LHP, GSH levels, and CAT activity were not found to be different between genders. Conclusions. We suggest that increased T-SH levels found in female rats may point to an adaptive reaction to oxidative damage, reflecting 8-OHdG and MDA overproduction. We are of the conviction that the increased 8-OHdG and MDA that we have determined in aged male rats may be a risk factor in the extent of oxidation in plasma.

LigaSure compared with ligatures and endoclips in experimental appendectomy: how safe is it?

PurposeThe present study aims to compare strength, healing, and inflammation of appendiceal stumps closed by LigaSure Precise™ (Valleylab, Boulder, CO, USA) device, ligatures using polyglactin 910 (Vicryl, Ethicon, Edinburgh, UK) and endoclips (Ligaclip ERCA, Ethicon, OH, USA), and operation time (OT) in experimental appendectomy.MethodsForty-eight Sprague–Dawley rats were divided into two (Group A and B). Each group was further subdivided into three subgroups (AS, AC, AL, BS, BC, BL) containing eight rats. Appendectomy was performed and stump was closed by ligatures in S, by endoclips in C and by LigaSure™ in L subgroups. OT was recorded. In Group A, cecum bursting pressures (BP) were determined instantly after the operation. In Group B, BP, histological evaluations, and measurements of collagen contents estimated by the tissue hydroxyproline (HPL) level were made on the seventh postoperative day. Statistical analyses were performed with Kruskal–Wallis test and Mann–Whitney U test. P value was considered significant at less than 0.05.ResultsBPs of subgroups were comparable on postoperative immediate period and day 7. HPLs and OTs were significantly better in L subgroups. BL had the least inflammation.ConclusionBetter healing, less inflammation, shorter OT, and equal strength achieved with LigaSure™ device comparing with polyglactin 910 ties and endoclips in experimental appendectomy is encouraging.

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.

Effect of tempol on redox homeostasis and stress tolerance in mimetically aged Drosophila

We aimed to test our hypothesis that scavenging reactive oxygen species (ROS) with tempol, a membrane permeable antioxidant, affects the type and magnitude of oxidative damage and stress tolerance through mimetic aging process in Drosophila. Drosophila colonies were randomly divided into three groups: (1) no D-galactose, no tempol; (2) D-galactose without tempol; (3) D-galactose, but with tempol. Mimetic aging was induced by d-galactose administration. The tempol-administered flies received tempol at the concentration of 0.2% in addition to d-galactose. Thiobarbituric acid reacting substance (TBARS) concentrations, advanced oxidation protein products (AOPPs), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), sialic acid (SA) were determined. Additionally, stress tolerances were tested. Mimetically aged group without tempol led to a significant decrease in tolerance to heat, cold, and starvation (P < 0.05), but tempol was used for these parameters. The Cu,Zn-SOD activity and SA concentrations were lower in both mimetically aged and tempol-administered Drosophila groups compared to control (P < 0.05), whereas there were no significantly difference between mimetically aged and tempol-administered groups. Mimetically aged group without tempol led to a significant increase in tissue TBARS and AOPPs concentrations (P < 0.05). Coadministration of tempol could prevent these alterations. Scavenging ROS using tempol also restores redox homeostasis in mimetically aged group. Tempol partly restores age-related oxidative injury and increases stress tolerance.

Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer

Nitric oxide synthase (eNOS/NOS3) is responsible for the endothelial synthesis of nitric oxide (NO•). G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO• production in NOS3 894T (298Asp) allele carriers compared with the GG homozygotes. NO• acts as an antioxidant protecting against Fentons reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individuals risk of laryngeal cancer (LC). In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn-superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR-RFLP. In LC patients with TT genotype, Cu, Zn-superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis.

Age-related changes in rat prostate tissue; perspective of protein oxidation.

Abstract Background: Increased systemic oxidative stress is considered as an important risk factor for prostate cancer occurrence; however, the relationship between impaired redox homeostasis of prostate tissue and aging remains unclear. Objective: In our study, we hypothesized that age-related deterioration of redox homeostasis in prostate tissue may be considered as a predisposing factor for prostate cancer occurrence. Methods: Sprague–Dawley rats were divided into two groups as young control (5 months) and naturally aged (24 months). We investigated the levels of oxidant and antioxidant parameters in prostate tissue. Results: Advanced oxidation protein products, protein carbonyl, non-protein thiol and lipid hydroperoxides levels of aged rats were significantly higher than in the young control rats (p < 0.01, p < 0.05, p < 0.001, p < 0.05, respectively). Additionally, antioxidant activity of Cu-Zn-superoxide dismutase in elderly group was significantly lower than young controls (p < 0.05). Conclusions: We suggest that increased non-protein thiol levels found in aged rats may prevent further dissemination of oxidative protein damage. We also propose that the increased levels of oxidative protein damage markers and decreased Cu-Zn superoxide dismutase activity in aged prostate may be considered as a predisposing factor for prostate cancer. Further studies are warranted to clarify all these oxidative changes as initiation factors for prostate cancer in the association of aging with prostate cancer.

The effects of lipoic acid on redox status in brain regions and systemic circulation in streptozotocin-induced sporadic Alzheimer’s disease model

AbstractWhile the deterioration of insulin-glucose metabolism (IGM), impaired redox homeostasis (IRH), β-amyloid accumulation was reported in Sporadic Alzheimer’s Disease (SAD) model, aforementioned factors related to lipoic acid administration and anthropometric indexes (AIs) are not yet studied with integrative approach. β-amyloid accumulation, redox homeostasis biomarkers and AIs are investigated in SAD model. Streptozotocin-induced inhibition of insulin-signaling cascade but not GLUT-2 and GLUT-3 transporters takes a role in β-amyloid accumulation. Inhibition types are related to IRH in cortex, hippocampus and systemic circulation. Lipoic acid (LA) shows both antioxidant and prooxidant effect according to the anatomical location. LA administration also leads to improved AIs during GLUT-2 inhibition and cortical redox status in GLUT-3 inhibited group. Optimal LA action could be possible if its redox behavior is balanced to antioxidant effect. Diagnostic usage of systemic IRH parameters as biomarkers and their possible correlations with deteriorated IGM should be investigated. Graphical abstractᅟ

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.