Pinar Atukeren

GSM Base Station Electromagnetic Radiation and Oxidative Stress in Rats

The ever increasing use of cellular phones and the increasing number of associated base stations are becoming a widespread source of nonionizing electromagnetic radiation. Some biological effects are likely to occur even at low-level EM fields. In this study, a gigahertz transverse electromagnetic (GTEM) cell was used as an exposure environment for plane wave conditions of far-field free space EM field propagation at the GSM base transceiver station (BTS) frequency of 945 MHz, and effects on oxidative stress in rats were investigated. When EM fields at a power density of 3.67 W/m2 (specific absorption rate = 11.3 mW/kg), which is well below current exposure limits, were applied, MDA (malondialdehyde) level was found to increase and GSH (reduced glutathione) concentration was found to decrease significantly (p < 0.0001). Additionally, there was a less significant (p = 0.0190) increase in SOD (superoxide dismutase) activity under EM exposure.

Cerebrospinal fluid superoxide dismutase and serum malondialdehyde levels in patients with aneurysmal subarachnoid hemorrhage : preliminary results

Abstract Objectives: Experimental studies provide evidence that oxidative damage plays a role in the development of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) but data from human studies is still limited. The purpose of this study was to investigate the time course of cerebrospinal fluid (CSF) superoxide dismutase (SOD) and serum malondialdehyde (MDA) changes in patients with aneurysmal SAH. Methods: SOD in CSF and MDA in the serum were detected on days 1–3, 5 and 7 after aneurysmal SAH in 21 patients, and the results were compared with 15 patients with hydrocephalus. The results were also compared with those of clinical parameters including the patients outcome at 6 months. Results: The mean CSF SOD levels were lower and serum MDA levels were higher than the controls. Patients with a high amount of blood within the cisterns had a trend to decreased SOD while increasing MDA levels. Conclusion: These preliminary results suggest that the levels of antioxidants are decreased after the onset of SAH in the early period, possibly because of increased oxidative stress. Reactive oxygen-mediated oxidative damage may play an important role in inflammation after SAH.

The effect of α-lipoic acid on NOS dispersion in the lung of streptozotocin-induced diabetic rats

Oxidative stress and impaired bioactivity of nitric oxide (NO) play an important role in the organ pathogenesis and angiopathic complications of diabetes mellitus. In this study, we evaluated the effects of alpha-lipoic acid (ALA) on nitric oxide synthase (NOS) in lung tissues. ALA is a strong antioxidant. We wonder how it can affect oxidative stress and NO in the lung cells and vessels of diabetic rats. Wistar rats were divided into four groups; control, diabetic [65 mg/kg streptozotocin (STZ) for 15 days], STZ+ALA-treated (65 mg/kg ALA every 2 days for 15 days), and ALA-only-treated animals. At the end of the experimental period, lipid peroxidation, superoxide dismutase (SOD), and inducible NOS (iNOS) and endothelial NOS (eNOS) distribution were evaluated. Oxidative stress decreased with ALA in diabetic animals, and SOD also increased with ALA. iNOS and eNOS increased in diabetic animals, and ALA prevented iNOS increment in lung tissues. As a result, ALA can prevent some diabetic effects on the lungs and can also protect from vascular damages.

Phosphodiesterase-5 inhibition by sildenafil citrate in a rat model of bleomycin-induced lung fibrosis

Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of bleomycin-induced lung fibrosis. Lung fibrosis was induced by intratracheal administration of 0.1 ml of bleomycin hydrochloride (5 mg/kg in 0.9% NaCl) under anesthesia to Sprague-Dawley rats (200-250 g; n = 7-8 per group). Control rats received an equal volume of saline intratracheally. In the treatment groups, the rats were treated with either sildenafil citrate (10 mg/kg per day; subcutaneously) or saline for 14 days. Another group of rats were administered subcutaneously with N(G)-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg in 0.9% NaCl) 5 min after sildenafil injections. After decapitation, the lungs were excised and taken for microscopic evaluation or stored for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity, and for the assessment of apoptosis. Trunk blood was collected for the assessment of serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels. In the group with lung fibrosis, the lung tissue was characterized by microscopic lesions, increased lipid peroxidation with a concomitant reduction in GSH content, increased MPO activity and apoptosis. Serum TNF-alpha and IL-1beta levels were higher in the lung fibrosis group compared to control values. Sildenafil reversed tissue MDA levels, MPO activity and serum pro-inflammatory cytokine levels, and preserved GSH content although its effect on the extent of tissue lesion and apoptosis was not statistically significant. Treatment with l-NAME reversed the effect of sildenafil on GSH content. In conclusion, sildenafil citrate administration to rats with bleomycin-induced lung fibrosis seems to be beneficial via prevention of lipid peroxidation, cytokine production and/or release and neutrophil accumulation.

The effect of sildenafil, a phosphodiesterase-5 inhibitor, on acetic acid-induced colonic inflammation in the rat

Background and Aim:  Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)‐dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant‐antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of acetic acid‐induced colitis.

Alterations in lipid peroxidation and antioxidant status in different types of intracranial tumors within their relative peritumoral tissues

OBJECTIVES Elevated levels of lipid peroxidation and changes in the concentration of enzymatic and non-enzymatic antioxidant systems have been reported in various cancers, but there are very few reports available of lipid peroxidation due to oxidative stress in patients with intracranial neoplasms. The purpose of this study was to assess alterations in lipid peroxidation and antioxidant status in different types of tumors and to compare the results with their relative peritumoral tissues and compare the oxidative status in different grades of tumors. PATIENTS AND METHODS We investigated the extent of oxidative stress and the levels of antioxidants in 16 astrocytomas and 38 other different types intracranial tumors comparing the results with their corresponding peritumoral tissues and comparing the levels in between low-grade and high-grade tumors. The extent of lipid peroxidation as evidenced by the formation of thiobarbituric acid-reacting substances (TBARS), as well as the status of the antioxidant systems such as superoxide dismutase (SOD), glutathione reductase (GR) and reduced glutathione (GSH) in tumor tissues and adjacent peritumoral tissues was estimated. The tumoral tissues were also compared as to their degrees of malignancy. RESULTS According to our results lipid peroxidation in brain tumor tissues was enhanced compared to the corresponding adjacent peritumoral tissues. This was accompanied by a significant tumoral decrease in both enzymatic and non-enzymatic antioxidants. The low levels of antioxidants in tumor tissues, might be related to an increased use of antioxidant systems to scavenge lipid peroxides. Also a striking elevation in TBARS levels, and decrease in SOD activity and GSH levels were seen in high-grade tumors when compared with low grades. CONCLUSION These findings emphasize a consistent difference in the level of antioxidants between the tumoral sample and its corresponding peritumoral tissue, independently of the tumoral type, and the most pivotal action would seem to minimise exposure to endogenous and exogenous sources of oxidative stress.

Expression of hypoxia inducible factor-1α in tumors of patients with glioblastoma multiforme and transitional meningioma

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the major transcriptional factor involved in the adaptive response to hypoxia. The aim of this study was to assess HIF-1alpha in 22 patients with transitional meningioma (TM) and 26 patients with glioblastoma multiforme (GBM). HIF-1alpha was assessed using a commercially available enzyme-linked immunosorbent assay-based HIF-1 transcription factor assay. Levels of HIF-1alpha in TM and GBM were measured using optical density at 450nm, and median values were found to be 0.35 for TM and 0.37 OD for GBM, respectively. There was no statistically significant difference between the two types of tumor (p=0.264). These findings indicate that HIF-1alpha is elevated in both TM and GBM, suggesting that although hypoxia is one of the most important and powerful stimuli for HIF-1alpha elevation and consequently angiogenesis, other mechanisms may play roles in HIF-1alpha stimulation in benign brain tumors such as TM.

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.

Redox Homeostasis of Albumin in Relation to Alpha-Lipoic Acid and Dihydrolipoic Acid

Albumin represents the predominant circulating antioxidant agent in plasma exposed to continuous oxidative stress and a change in serum albumin structure accounts for its antioxidant properties. Alterations in the redox status of albumin may result in impairments of its biological properties. Alpha-lipoic acid (LA), a naturally occurring thiol compound found in virtually all species, is a potent antioxidant with high efficacy which is also involved in the chelation of metal ions, regeneration of antioxidants, and repair of oxidatively damaged proteins. In human body LA is rapidly reduced to dihydrolipoic acid (DHLA) after intake into the cell. Both, LA and DHLA are amphipathic molecules which act as antioxidants both in hydrophilic and lipophilic environments. The present study aimed to investigate the antioxidant/pro-oxidant effects of LA and DHLA due to their concentrations in metal-catalyzed protein oxidation (MCO) of human serum albumin (HSA). Progressive oxidative modification of albumin was found in MCO system by an increased content of protein hydroperoxides (POOH), protein carbonyl groups (PCO) which is the formers major breakdown product, and other protein oxidation markers such as advanced oxidized protein products (AOPP) and protein thiol groups (P-SH). The possible antioxidant protective effects of LA and DHLA were observed with 25 microM and 50 microM; DHLA being more influential. Protein oxidation parameters were found to be lower and P-SH levels seemed higher. However, prooxidant effects of both LA and DHLA came on the scene with increased concentrations of 75 microM and 100 microM where the latter seemed the most hazardous with contradicted results. It is clear that the loss of biological activity of human serum albumin by MCO system appears of medical relevance and if LA exerts similar effects seen in the present study, it is possible that cellular prooxidant activity can also result consuming this unique antioxidant in certain doses.

Relationship between DNA damage and total antioxidant capacity in patients with transitional meningioma

PURPOSE The purpose of this study was to assess oxidative DNA damage and total antioxidant capacity (TAC) in patients with transitional meningioma (TM) and to compare the results with normal brain tissues. PATIENTS AND METHODS Oxidative DNA damage and TAC were evaluated in TM extracted from 22 patients and in normal brain tissues of 15 subjects who underwent autopsy within first 4h of death. Oxidative DNA damage was assessed by measuring 8-hydroxy-2-deoxyguanosine (8-OH-dG) using the 8-OH-dG enzyme immunoassay kit, a quantitative assay for 8-OH-dG, and TAC was analyzed using the ImAnOx colorimetric test system for the determination of antioxidative capacity. The results were compared between two groups and any correlation between 8-OH-dG and TAC was sought. RESULTS The median level of TAC in TM (135nmol/gwet tissue) was remarkably lower than in normal brain tissue (298nmol/gwet tissue). The difference was statistically significant (p=0.00001). In contrast, oxidative DNA damage was significantly higher in patients with TM (71.61ng/gwet tissue) than in controls (34.71ng/gwet tissue). Again, the difference was statistically significant (p=0.00001). We also found a negative correlation between oxidative DNA damage and TAC (p<0.001). CONCLUSION These findings show that the degree of oxidative DNA damage is increased and TAC is decreased in TM and oxidative DNA damage is negatively correlated with the levels of TAC.