Rapid Communication: oxidative stress induced by mixed exposure to glyphosate and silver nanoparticles

Objective: The pathogenesis of Behçet’s disease (BD) may be related to excessive production of reactive oxygen species, activated neutrophils, and T lymphocytes. The goal of this prospective study was to investigate whether there is any relationship among the oxidant/antioxidant system and nitric oxide (NO) and malondialdehyde (MDA) levels in patients with BD and its subtypes: complete Behçet’s disease (CBD) and incomplete Behçet’s disease (ICBD), with or without ocular disease. Methods: Thirty-two patients and 26 age- and sex-matched healthy control subjects were evaluated for NO and MDA levels and antioxidant enzyme activities. The patients with BD were divided into two subgroups: those with and without ocular disease. Twelve patients with CBD and 4 patients with ICBD had ocular disease. The serum NO level was determined by Griess reaction. The MDA level was detected by thiobarbituric acid reaction. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum were analyzed with spectrophotometric methods. Results: Increased MDA levels but decreased GSH-Px activities in plasma were observed in BD patients with all subtypes, as compared with controls. Concerning the presence of ocular disease and the subtype (CBD or ICBD) compared with each other, there were no significant differences in MDA or NO serum levels and SOD or GSH-Px enzyme activities. Conclusions: Serum NO levels and SOD enzyme activities were not significantly changed in patients with BD and its subtypes; however, a remarkable decrease of GSH-Px enzyme activity and increase of MDA levels were found.

To investigate the effects of blocking lactate synthesis on the HT22 cell injuries caused by hypoxia. 2-deoxy-D-glucose (2-DG) is a non-metabolized glucose analogue that can inhibit lactate synthesis by blocking glycolysis. HT22 cells were divided into 4 groups: Control group, 2-DG group, Hypoxia group and 2-DG+Hypoxia group. The cells in control group and 2-DG treatment group were cultured in a 37℃, 5% CO2 incubator, and thecells in hypoxia group and 2-DG + Hypoxia group were cultured in a hypoxia incubator. The concentrations of 2-DG were 2.5 and 5 mmol/L, the concentration of oxygen was 0.3%, and the treatment time was 24 h. Cell activity was detected by CCK-8 assay, the levels of lactate in cell culture medium were detected by spectrophotometry, cell morphology was observed by fluorescence staining, the level of reactive oxygen species (ROS) was detected by flow cytometry, and the activities of superoxide dismutase (SOD) and catalase (CAT) were determined by enzyme activity kits. The protein expression levels of p-p38, t-p38 and β-actin were detected by Western blot. Compared with that in control group, the lactate level in culture medium and cell activity were decreased significantly (P＜0.01), the number of adherent cells was decreased, the level of ROS was increased (P＜0.01), and the enzyme activity of CAT was decreased (P＜0.05) in the 2-DG group. In the hypoxia group, the level of lactate in the culture medium was increased significantly (P＜0.01), the cell activity was decreased (P＜0.01), the number of adherent cells was decreased, the ROS levels were increased (P＜0.01), and the enzyme activities of CAT and SOD were decreased (P＜0.01 or P＜0.05). In 2-DG+Hypoxia group, the level of lactate was decreased significantly (P＜0.05), the cell viability was decreased significantly (P＜0.01), the number of cells was decreased significantly, and the ability of adhere to the wall was weakened significantly. The level of ROS was increased significantly (P＜0.01), the enzyme activities of CAT and SOD were decreased significantly (P＜0.01), the protein expression level of p-p38 was increased significantly (P＜0.05), and there was no change in t-p38. Compared with hypoxia groups, in 2-DG combined with hypoxia group, the level of lactate induced by hypoxia, the cell activity, and the enzyme activity level of CAT were decreased significantly (all P＜0.01), while the level of ROS was increased significantly (P＜ 0.01). Blocking lactate can reduce the cell activity level under hypoxia and aggravate the oxidative stress injury of HT22 cells. The mechanisms may be related to increasing ROS level and activating p38 signal pathway.

Background: Quercetin has antioxidant and anti-inflammatory effects. Although there are previous animal experi-ments investigating Quercetin’s effect on ischemia reperfusion (IR) injury in the literature, studies involving effect of lower extremity IR on remote organ are rare.Materials and Methods: 18 male Wistar Albino rats were randomly divided into 3 groups, 6 in each group as; Cont-rol (C), Ischemia-reperfusion (IR), IR-Quercetin, (IR-Q). Their weights were between 200-250 g. 30 minutes before the procedure20 mg/kgQuercetin was administered via intraperitoneal route. In the IR groups, infrarenal abdomi-nal aorta was clamped by an atraumatic microvascular clamp. After 120 minutes of ischemia and reperfusion was achieved for another 120 minutes. When reperfusion period ended, tissue samples were taken from the lungs. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activity and histopathological parameters were compared.Results: We found the MDA level in the IR group higher than the control group (p<0.0001). Lower MDA level was found in the IR-Q group compared tothe IR group (p=0.012). SOD and CAT enzyme activity in the IR group was notably lower in the control group (p<0.0001, p<0.001, respectively). Higher SOD and CAT enzyme activities were found in the IR-Q group compared to the IR group (p=0.012, p<0.001, respectively). Neutrophil infiltra-tion/aggregation, alveolar wall thickness and total lung injury score were notably higher in IR group than in C group (p=0.001, p=0.002, p<0.0001, respectively). In addition, a statistically significant decrease was observed in the Quercetin treated group in neutrophil infiltration/aggregation, alveolar wall thickness and total lung injury score compared to the IR group (p=0.023, p=0.022, p=0.002, respectively).Conclusions: We determined that intraperitoneally administered Quercetin at a dose of 20 mg/kg30 minutes before ischemia in rats reduces lipid peroxidation, oxidative stress and reduces the damage caused by IR in lung histo-pathology.Study findings suggest that Quercetin has a lung protective effect when administered before IR.

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus.

Cells exposed to ultraviolet A (UVA) radiation can induce the production of reactive oxygen species (ROS) that may damage cellular elements. By contrast, antioxidants can reduce production of ROS. To assess these cellular events in a model system, rats were divided into three groups comprising control (C), ultraviolet exposed (UV), and ultraviolet exposed and quercetin-treated (UV + Q). UV and UV + Q group rats were irradiated 4 h/day with UVA radiation (1.25 mW/cm2) for 9 days. In the UV + Q group rats quercetin (50 mg/kg body weight) was administered intraperitoneally before irradiation. The levels of malondialdehyde (MDA) were increased significantly following irradiation (P < 0.001). In the UV + Q group MDA levels declined significantly compared with the UV group (P < 0.001). With respect to levels of glutathione (GSH), no statistically significant changes were found between the control and the UV group. The GSH levels in the UV + Q group were slightly higher than those of the control and UV groups, but not significantly so. The enzyme activities of glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase decreased significantly after irradiation (P < 0.001). In the UV + Q group all of these enzyme activities were found to be considerably higher than those in the UV group (P < 0.001). This study demonstrates that exposure of rats to UVA leads to oxidative stress as reflected by increased MDA levels and reduced enzymatic antioxidant levels. It also shows that quercetin may be useful in reducing or preventing photobiologic damage.

Uranium is a highly radioactive heavy metal that is toxic to living things. In this study, physiological, cytogenetic, biochemical and anatomical toxicity caused by uranium and the protective role of sage (Salvia officinalis L.) leaf extract against this toxicity were investigated with the help of Allium test. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) formation, chromosomal aberrations (CAs), superoxide dismutase (SOD) and catalase (CAT) enzyme activities, malondialdehyde (MDA) levels and changes in root meristem cells were used as indicators of toxicity. In the experimental stage, a total of six groups, one of which was the control, were formed. Group I was treated with tap water, while group II and III were treated only with sage (190 mg/L and 380 mg/L). Groups IV, V and VI were germinated with uranyl acetate dihydrate (0.1 mg/mL), uranyl acetate dihydrate + 190 mg/L sage and uranyl acetate dihydrate + 380 mg/L sage, respectively. Allium cepa L. bulbs of each group were germinated for 72 h, and at the end of the period, routine preparation techniques were applied and physiological, cytogenetic, biochemical and anatomical analyzes were performed. As a result, uranium application caused a significant decrease (p < 0.05) in all physiological parameters and MI values. MN, CAs numbers, SOD and CAT enzyme activities and MDA levels increased significantly (p < 0.05) with uranium application. Uranium promoted CAs in the root tip cells in the form of fragment, vagrant chromosome, sticky chromosome, bridge and unequal distribution of chromatin. In addition, it caused anatomical damages such as epidermis cell damage, cortex cell damage and flattened cell nucleus in root tip meristem cells. Sage application together with uranium caused significant (p < 0.05) increases in physiological parameters and MI values and significant decreases in MN, CAs, SOD and CAT activities and MDA levels. In addition, the application of sage resulted in improvement in the severity of anatomical damages induced by uranium. It was determined that the protective role of sage observed for all parameters investigated was even more pronounced at dose of 380 mg/L. The protective role of sage against uranium toxicity is related to its antioxidant activity, and sage has 82.8% metal chelating and 72.9% DPPH removal activity. As a result, uranyl acetate exhibited versatile toxicity in A. cepa, caused cytotoxicity by decreasing the MI rate, and genotoxicity by increasing the frequencies of MN and CAs. And also, Sage acted as a toxicity-reducing agent by displaying a dose-dependent protective role against the toxic effects induced by uranyl acetate.

Objectives:To investigate the role of oxidative stress on pseudoexfoliation formation and progression from pseudoexfoliation syndrome (XFS) to pseudoexfoliation glaucoma (XFG).Materials and Methods:This study investigated oxidative stress biomarkers in blood samples from 58 patients with XFG, 47 patients with XFS, and 134 healthy age- and sex-matched controls.Results:The highest serum malondialdehyde (MDA) levels were measured in XFG patients (p<0.001), and MDA level was higher in XFS patients than controls (p<0.001). Superoxide dismutase (SOD) and catalase (CAT) enzyme activities were significantly lower in XFS and XFG patients than in the control group, whereas a significant increase was observed in glutathione (GSH) levels (p<0.001 for all). However, levels of these three biomarkers did not differ significantly between XFS and XFG patients (p=0.188, p=0.185, and p=0.733, respectively). Nitric oxide (NO) concentration was significantly lower in XFG patients compared to XFS patients and controls (p<0.001) but did not differ between XFS patients and controls (p=0.476).Conclusion:Elevated MDA levels suggest that lipid peroxidation is important in XFS and XFG development and progression from XFS to XFG. In addition, reduction in SOD and CAT enzyme activities is considered a deficiency in the enzymatic antioxidant protection system. Furthermore, GSH values may be evaluated as a compensatory response to oxidative stress in XFS and XFG. Alterations in NO indicate the role of a vascular regulatory factor in the progression from XFS to glaucoma.

Oxidative stress is defined as over-production of free radicals which lead to cells damage, pathological condition and cell death. The objective of this study was to analyze respond of oxidative stress and isoflavone treatment on superoxide dismutase (SOD) enzyme activities and lipid peroxidation in rat liver. A total of fifteen male Spraque Dawley rats were used in this study. They were sub-divided into three groups; (1) a negative control group, (2) a stress oxidative group, and (3) treatment by stress condition followed by treatment with isoflavone. Stress condition was achieved by five days fasting together with swimming for 5 mins/day and only drinking water ad libitum. Isoflavone was orally administrated on a dose of 1 mg/200g bw/day for five days. At the end of the experiment, rats were sacrificed by anesthesia. Liver was collected for analysis of SOD enzyme activities, SOD immunohistochemical analysis, and malondialdehyde (MDA) level. Result showed that stress condition increase free radicals that showed by decreased SOD activity, and increased MDA level. Isoflavone treatment could get over reduction of SOD and prevented increase of MDA level in the liver of rats under stress conditions. Key Words: Oxidative Stress, Isoflavone, Rat, Superoxide Dismutase, Malondialdehyde

Over the past 10 to 15 years, a vast collection of studies have provided evidence indicating that reactive oxygen species (ROS), particularly superoxide (O2·−) and hydrogen peroxide (H2O2), contribute to the pathogenesis of cardiovascular diseases, such as heart failure and hypertension. Griendling et al1 first demonstrated that NADPH oxidase present in the vasculature is a primary source of the elevated ROS levels. Since these initial studies, NADPH oxidase-derived ROS in the kidney,2 heart,3 and brain4 have been linked to the development and progression of numerous cardiovascular-related diseases. More recently, however, mitochondria have also been identified as important sources of ROS in controlling cardiovascular function. Considering that mitochondria are the primary source of ROS in most cells during normal respiration because of the leaking of electrons from the electron transport chain (ETC), perhaps it should not be all that surprising that mitochondrial-produced ROS are involved in pathophysiological conditions of the cardiovascular system. To date, most of the evidence linking mitochondrial dysfunction and mitochondrial-produced ROS to the pathogenesis of cardiovascular diseases comes from studies on the peripheral renin-angiotensin system.5 For example, using a model of cardiac ischemic reperfusion injury, Kimura et al6 reported that angiotensin II (Ang II)-induced preconditioning is mediated by mitochondrial-produced ROS. The authors further demonstrated that Ang II-induced NADPH oxidase-derived ROS lie upstream of mitochondrial-produced ROS, thus, implicating a ROS-induced ROS mechanism. Similarly, it was demonstrated recently that, in aortic endothelial cells, Ang II-induced NADPH oxidase activation leads to an increase in mitochondrial ROS production, as well as mitochondrial dysfunction, as determined by a decrease in mitochondrial membrane potential and mitochondrial respiration.7 Together, these studies and others (detailed elsewhere5) clearly illustrate a role for mitochondrial-produced ROS and mitochondrial dysfunction in peripheral tissues in the pathogenesis of …

This series of debates was initiated for the Journal of Applied Physiology because we believe an important means of searching for truth is through debate where contradictory viewpoints are put forward. This dialectic process whereby a thesis is advanced, then opposed by an antithesis, with a

Albumin-bound fatty acids induce mitochondrial oxidant stress and impair antioxidant responses in proximal tubular cells

Antiapoptotic and antioxidant effects of β-carotene against methotrexate-induced testicular injury

Sulfiredoxin1 (Srxn1), an endogenous antioxidant protein, is involved in cardiovascular diseases. In this study, we aimed to investigate the role of Srxn1 in VSMCs and its molecular mechanism. The murine vascular smooth muscle cells MOVAS were treated with different doses of platelet-derived growth factor-BB (PDGF-BB); then, Srxn1 expression was detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. MTT and wound healing assay were used to examine the effect of Srxn1 on MOVAS cell proliferation and migration. Reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity in MOVAS cells were detected using corresponding commercial kits. Moreover, the expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2), and nuclear factor erythroid-2-related factor 2 (Nrf2) /antioxidant response element (ARE) signaling-related proteins was detected using western blot analysis. In our study, PDGF-BB dose-dependently increased Srxn1 expression in MOVAS cells, and Srxn1 expression was increased with time dependence in PDGF-BB-treated MOVAS cells. The knockdown of Srxn1 increased PDGF-BB-induced the proliferation, migration, ROS production, MDA level, and the protein expression of PCNA and MMP-2, as well as decreased SOD activity and the expression of Nrf2/ARE signaling-related proteins in PDGF-BB-stimulated MOVAS cells. However, the overexpression of Srxn1 showed the opposite results to those of knockdown of Srxn1. Moreover, the inhibitory effects of Srxn1 overexpression on PDGF-BB induced proliferation, migration, ROS production, and MDA level and the promotion of Srxn1 overexpression on PDGF-BB induced SOD activity were partially reversed by the knockdown of Nrf2. Srxn1 inhibited PDGF-BB-induced proliferation, migration, and oxidative stress through activating Nrf2/ARE signaling.

In this study, the toxicity of the trace element zinc (Zn) in Allium cepa L. test material was examined. Toxicity was investigated in terms of physiological, cytogenetic, biochemical, and anatomical aspects. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) frequency, chromosomal abnormalities (CAs), malondialdehyde (MDA), proline and chlorophyll levels, superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and meristematic cell damage were used as indicators of toxicity. Additionally, the comet test was used to measure the degree of DNA damage. Four groups of A. cepa bulbs-one for control and three for applications-were created. While the bulbs in the treatment groups were germinated with Zn at concentrations of 35, 70, and 140mg/L, the bulbs in the control group were germinated with tap water. Germination was carried out at room temperature for 72h and 144h. When the allotted time was over, the root tips and leaf samples were collected and prepared for spectrophotometric measurements and macroscopic-microscopic examinations. Consequently, Zn treatment led to significant reductions in physiological indicators such as weight gain, root length, and germination percentage. Zn exposure caused genotoxicity by decreasing the MI ratios and increasing the frequency of MN and CAs (p < 0.05). Zn promoted various types of CAs in root tip cells. The most observed of CAs was the sticky chromosome. Depending on the dose, Zn was found to cause an increase in tail lengths in comet analyses, which led to DNA damage. Exposure to Zn led to a significant decrease in chlorophyll levels and an increase in MDA and proline levels. It also promoted significant increases in SOD and CAT enzyme activities up to 70mg/L dose and statistically significant decreases at 140mg/L dose. Additionally, Zn exposure caused different types of anatomical damage. The most severe ones are epidermis and cortex cell damage. Besides, it was found that the Zn dose directly relates to all of the increases and decreases in physiological, cytogenetic, biochemical, and anatomical parameters that were seen as a result of Zn exposure. As a result, it has been determined that the Zn element, which is absolutely necessary in trace amounts for the continuation of the metabolic activities of the organisms, can cause toxicity if it reaches excessive levels.

Dexmedetomidine (dex) is a potent, highly selective and specific α2-adrenoreceptor agonist. This experimental study was designed to investigate protective and therapeutic effect of two different doses of dex, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Male Sprague−Dawley rats were divided into four groups, each including 10 animals: control group, ischemia-reperfusion (I/R) group; treated groups with 10 μg/kg of dex and 100 μg/kg of dex. After removing right kidney of the rats, the left kidney has performed ischemia during 40 min and reperfusion in the following 3 h. The histopathological findings, and also tissue superoxide dismutase (SOD) and catalase (CAT) enzyme activity, malondialdehyde (MDA), glutathione (GSH), serum blood urea nitrogen (BUN), creatinine (Cre) and tumor necrosis factor-alpha (TNF-α) levels were determined. In the I/R group, compared to the control group, levels of BUN, Cre and kidney tissue MDA have increased significantly, SOD, CAT enzyme activity and glutathione levels have decreased significantly. In the dex10 group, compared to the I/R group, levels of Cre and TNF-α have decreased significantly, while the SOD activity has increased significantly. In the dex100 group, compared to the I/R group, levels of BUN, Cre have decreased significantly, while the SOD activity has increased significantly. In the I/R group, there was also extensive tubular necrosis, glomerular damage in the histological evaluation. Dex ameliorated these histological damages in different amounts in two treatment groups. In this study, the protective effects of dex against renal I/R injury have been evaluated by two different amount of doses.