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EN
Chlorfenvinphos is an organophosphate insecticide, posing a risk to those who are professionally involved in its production and use in agriculture, as well as to the general population. Organophosphates (OPs) are the class of insecticides, whose primary target is acetylcholinesterase (AChE) that hydrolyzes acetylcholine, a major neurotransmitter at the central and peripheral neuronal synapses. Moreover, many authors postulate that these compounds, both in acute and chronic intoxication, change the activities of antioxidative enzymes, thus leading to the enhancement of lipid peroxidation in many tissues. In the current study, animals received once a day, intragastrically with a stomach tube, 0.1ml/100g of olive oil (control groups) and oil solution of chlorfenvinphos at a dose of 0.02LD50 (0.3 mg/kg b. w.) - the experimental groups. The animals were sacrificed on day 14 or on day 28 of exposure. In the kidneys of rats, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) as well as reduced glutathione level (GSH) were determined. Chlorfenvinphos administration resulted in increased activities of antioxidative enzymes in the kidney of rats. Renal activities of SOD, GPx and GR were more pronounced on day 28 of chlorfenvinphos exposure than on day 14. The kidney reduced glutathione level (GSH) did not change in comparison to the control level. The current experimental findings indicate that subchronic administration of chlorfenvinphos leads to an adaptive response in the kidney of rats and this response is mostly due to reduced glutathione level and glutathione metabolism.
EN
Organophosphate compounds are nowadays the most frequently used pesticides. For these insecticides, the primary target is acetylcholinesterase and for this reason the main clinical effect of acute intoxication with organophosphate insecticides involves an irreversible inhibition of the activity of this enzyme. However, in the chronic or subchronic exposition oxidative stress has been reported as the main mechanism of its toxicity. The present study investigated the effect of three low doses (0.2, 2, 5 mg/kg bw) of chlorpyrifos for 14 or 28 days on serum liver enzymes and on oxidative stress parameters in the liver of rats. Chlorpyrifos treatment resulted in aminotransferases and alkaline phosphatase increase after 14 days (higher doses) and 28 days (all doses) treatment together with changes of antioxidative enzymes activities and reduced glutathione and malonyldialdehyde level in the liver. The enhancement of lipid peroxidation is temporary, reaching a peak after 14 days and decreasing after 28 days of treatment. Based on the experimental findings of this study the temporary liver injury caused by oxidative stress has been shown. The disturbances in the liver antioxidative status and increased liver membrane permeability may appear in case of doses near to the accepted human daily intake.
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Content available Pathogenesis of Reactive Oxygen Species: A Review
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Oxidative stress is known top-lay an important role in the development and pathogenesis of several chronic diseases such as diabetes, neurodegenerative diseases, and cancer. Exposure to poisons and toxicants results in the generation of pro-oxidant which eventually cause dysfunction in enzymatic activities and defect in the DNA, resulting to alteration in the expression of genes the induction of oxidative stress is by far associated with modern life styles which include the consumption and exposure to chemicals which are used to preserve and process food. Hence, this review provides insight to the relationship between reactive oxygen species and some chronic disorders. That is the contribution of reactive oxygen species to the pathogenesis of some diseases.
EN
Nucleus accumbens (NAcc) are a collection of neurons that form the main part of the ventral striatum, which is a significant dopaminergic structure. Also, NAcc is thought to play an important role in reward, pleasure, laughter, addiction, aggression, fear, and the placebo effect. In the present work we were interested in studying the effects of a 6-OHDA induced lesion in the nucleus accumbens (NAcc), which is known as an important dopaminergic structure, on a specific behavioral task that involves both short term and long term spatial memory (the radial-8-arm-maze task), as well as on the oxidative stress markers (two antioxidant enzymes: superoxide dismutase-SOD and glutathione peroxidase-GPX and a lipid peroxidation marker: malondialdehyde-MDA, as well as the total antioxidant status-TAS) from the temporal lobe, which is considered to be the most vulnerable cortical area to oxygen levels fluctuations and hypoxia. Our results showed some significant effects of this lesion on the reference memory errors and time necessary to finish the test in the radial-8-arm-maze task. Additionally, increased oxidative stress status was demonstrated in the temporal lobe of the lesioned rats, as demonstrated by the high levels of lipid peroxidation and decreased total antioxidant status. Moreover, significant correlations are reported here between the behavioral parameters which we studied in the radial-8-arm-maze task and the aforementioned oxidative stress markers.
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Although it is accepted that an important correlation exists between the physical exercise and the oxidative stress status, the data regarding the levels of the main oxidative stress markers after physical training have been difficult to interpret and a subject of many controversies. There are also very few studies regarding the effects of short-time exercise on the oxidative stress status modifications. Thus, in the present report we were interested in studying the modifications of some oxidative stress markers (two antioxidant enzymes-superoxide dismutase and glutathione peroxidase, a lipid peroxidation parameter - malondyaldehide, the total antioxidant status and protein carbonyl levels), from the serum of rats that were subject to one bout of five minutes exercise on a treadmill, when compared to a control sedentary group. In this way, we observed a decrease of superoxide dismutase specific activity in the rats which performed the exercises. Still, no modifications of glutathione peroxidase specific activity were found between groups. In addition, increased levels of malondyaldehide and protein carbonyls were observed in the rats subjected to exercises. In conclusion, our data provides new evidence regarding the increase of the oxidative stress status, as a result of a 5-minutes bout of treadmill exercising in rats, expressed through a decrease in the SOD specific activity and the total antioxidant status and also an increase of the lipid peroxidation and protein oxidation processes.
EN
Background: Diabetes mellitus is a global health concern affecting 173 million adults annually that requires effective treatment. Medicinal plants such as ginger and curcumin are rich in bioactive compounds that have therapeutic potential. The aim of this study was to evaluate the therapeutic potential of ginger and curcumin extracts in diabetic nephropathy in the rat model. Material and methods: High-performance liquid chromatography was used to examine ginger and curcumin extracts. Fifty male Sprague Dawley rats were divided into five groups: control, untreated diabetic, ginger-treated diabetic, curcumin-treated diabetic and a ginger + curcumin combination group. Diabetes was induced with a single intraperitoneal dose of streptozotocin. Rats received daily oral doses of ginger, curcumin or the combination of both. After sixteen weeks, rats were anesthetized and various tests were conducted to evaluate treatment outcomes. Results: The rats treated with combined ginger and curcumin extracts had superior outcome in terms of more antioxidant activity, better glycemia management and less DN-related kidney damage (reduced albuminuria and less histological changes). Conclusions: Our findings indicate that ginger and curcumin extracts have therapeutic potential in mitigating functional and structural alterations in the kidneys of diabetic rats, possibly due to their anti-diabetic and anti-inflammatory properties.
EN
Genetic variations of the antioxidant enzymes may influence the susceptibility to oxidative stress and consequently the development and progression of diabetic complications. The aim of the current study was to test the association between the −262C/T polymorphism in the catalase gene promoter and carotid atherosclerosis in Slovenian patients with type 2 diabetes. Two-hundred and eighty six diabetics and 150 healthy controls were enrolled in the study. Carotid atherosclerosis was quantified ultrasonographiocally by carotid intima-media thickness (CITM), plaque score and plaque type. Genotypes were determined using the real-time PCR. Fibrinogen concentration showed a borderline statistically significant difference due to catalase genotypes (p=0,05). No difference in clinical characteristics, CIMT, plaque stability or plaque score was observed. Logistic regression model adjusted for age, gender, smoking, BMI, lipid parameters and duration of hypertension and diabetes showed significant association of T allele and lower risk for higher plaque score (OR=0,25; p=0,025). No association with CIMT>1mm and unstable plaques was observed. T allele of −262C/T is associated with lower risk for higher plaque score but it did not affect clinical parameters, CIMT and plaque stability. Whether this polymorphism can be used as a genetic marker for advanced carotid atherosclerosis in diabetic patients needs to be evaluated in the future.
EN
In addition to its known classical roles, the renin angiotensin system (RAS) has more subtle functions which include the regulation of emotional responses. Previous studies regarding the anxiety related behavior of RAS have showed controversial results. There is also evidence that oxidative stress accompanies angiotensin II infusion, but the role of AT1/AT2 specific receptors is not clear. The aim of this study was to evaluate the effects of central angiotensin II receptor blockers on anxiety state and oxidative stress. Behavioral testing included elevated plus maze, while oxidative stress status was measured though the extent of a lipid peroxidation product (malondialdehyde-MDA) and the specific activity of some defense antioxidant enzymes (superoxide dismutase-SOD and glutathione peroxidase-GPx). The rats treated with angiotensin II spent significantly less time in the open-arms of elevated-plus-maze, while the administration of losartan resulted in a significant increase of this time. We observed a significant increase of MDA concentration in the angiotensin II group and a decrease of MDA levels in both losartan and PD-123177 groups. In addition, a significant correlation was seen between the time spent in the open arms and oxidative stress markers. These findings could lead to important therapeutic aspects regarding the use of angiotensin II receptor blockers in anxiety-related disorders.
EN
In the current study, we evaluated the dynamics of oxidative stress markers in patients with acute myocardial infarction (AMI) treated by primary percutaneous coronary intervention (PCI). Thirty consecutive patients with AMI with ST elevation were included. Plasma lipid peroxidation end product malondialdehyde (MDA) and total antioxidant capacity (TAC) in blood plasma were evaluated. Peripheral venous blood samples were obtained prior to reperfusion and at five time points after reperfusion. The control group consisted of 20 ischemic patients without acute coronary syndrome. TAC in the AMI group at admission was lower than in control patients (1.26 + 0.32 vs. 1.52 + 0.24 mmol/l). Within 1 h after reperfusion, in most cases, values significantly declined (1 min, 1.10 + 0.33 mmol/l; 1 h, 1.06 + 0.21 mmol/l [p= 0.03]). After 3 h, values began to increase (1.14 + 0.29 mmol/l) and returned to basal values after 3 d (1.29 + 0.24 mmol/l). MDA levels in AMI patients at admission were higher than in control patients (1.66 + 0.55 vs. 1.44 + 0.55 mmol/l) but showed a sustained decrease over the 3 h after reperfusion of the occluded artery (1 min, 1.57 + 0.37 mmol/l; 1 h, 1.50 + 0.35 μmol/l; 3 h, 1.35 + 0.59 μmol/l [p = 0.03]). Reperfusion of the occluded coronary artery by PCI in AMI lead to an immediate decrease in TAC, suggesting formation of reactive oxygen species. However, the MDA level significantly decreased after reperfusion. This may suggests less reperfusion injury after PCI.
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Atopic dermatitis is characterized by impaired skin and mucous membrane barrier function. Measures improving barrier integrity decrease the influence of environmental factors that might exacerbate inflammation. Ten adult patients with mild-to-moderate atopic dermatitis consumed for three months fermented with potent antioxidative probiotic, L. fermentum ME-3 (DSM 14241) goat milk 200 mg/day. A control group consisted of six patients, not supplemented by probiotic. All patients used emollients regularly. Skin iron levels, glutathione redox ratios (GSSG/GSH), diene conjugate (DC) amounts, blood glutathione status, oxidized low-density lipoprotein (oxLDL), and total antioxidativity was measured at the baseline and after three months. A significant decrease in skin iron levels, DC amounts, and glutathione redox ratio occurred in the probiotic-supplemented group compared to the control group (P < 0.05 for all indices). In the same group, blood levels of oxLDL decreased (p < 0.05), and GSH levels increased (P < 0.001) with concomitant improvement in the GSSG/GSH ratio. Blood antioxidativity markers also showed an improvement. The results of our study demonstrate that regular use of probiotics with antioxidative properties coupled with the use of lipid-containing emollients considerably decreases inflammation and concomitant oxidative stress in adult patients with mild-to-moderate atopic dermatitis. This effect was observed both in the skin and in the blood.
EN
The present study aimed to investigate the relationship between semen quality parameters and DNA integrity, and determine whether semen quality parameters could serve as a reliable biomarker for monitoring sperm DNA damage. Conventional semen parameters from a total of 202 male human subjects were analyzed. DNA fragmentation and 8-oxo-7,8-dihydro-2′- deoxyguanosine (8-oxoGuo) were used to assess sperm DNA integrity. DNA fragmentation was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and sperm chromatin structure assay (SCSA), while 8-oxodGuo was quantified by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) coupled with an on-line solid phase system. The levels of 8-oxodGuo levels in sperm were related to the percentages of DNA fragmentation measured by both the TUNEL and SCSA (r = 0.22, p = 0.048; r = 0.12, p = 0.039). Sperm vitality, motility and morphology from all of the participants exhibited a weak correlation with the levels of 8-oxodGuo and the percentages of DNA fragmentation. Semen quality parameters may be independent of the formation of DNA fragmentation and oxidative adducts in sperm. Semen quality parameters may be insufficient to monitor sperm DNA fragmentation and oxidative damage. DNA damage in sperm is recommended to be included in routine measurements.
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Content available remote Melatonin protection against burn-induced liver injury. A review
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EN
Severe thermal injury may be complicated by dysfunction of organs distant from the original burn wound, including the liver, and represents a serious clinical problem. Although pathophysiology of burn-induced liver injury remains unclear, increasing evidence implicate activation of inflammatory response, oxidative stress, endothelial dysfunction and microcirculatory disorders as the main mechanisms of hepatic injury. Several studies suggest melatonin as a multifunctional indolamine that counteracts some of the pathophysiologic steps and displays significant beneficial effects against burn-induced cellular injury. This review summarizes the role of melatonin in restricting the burn-induced hepatic injury and focuses on its effects on oxidative stress, inflammatory response, endothelial dysfunction and microcirculatory disorders as well as on signaling pathways such as regulation of nuclear erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappaB (NF-kB). Further studies are necessary to elucidate the modulating effect of melatonin on the transcription factor responsible for the regulation of the pro-inflammatory and antioxidant genes involved in burn injuries.
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Content available remote Protein Disulfide Isomerase Superfamily in Disease and the Regulation of Apoptosis
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EN
Cellular homeostasis requires the balance of a multitude of signaling cascades that are contingent upon the essential proteins being properly synthesized, folded and delivered to appropriate subcellular locations. In eukaryotic cells the endoplasmic reticulum (ER) is a specialized organelle that is the central site of synthesis and folding of secretory, membrane and a number of organelletargeted proteins. The integrity of protein folding is enabled by the presence of ATP, Ca++, molecular chaperones, as well as an oxidizing redox environment. The imbalance between the load and capacity of protein folding results in a cellular condition known as ER stress. Failure of these pathways to restore ER homeostasis results in the activation of apoptotic pathways. Protein disulfide isomerases (PDI) compose a superfamily of oxidoreductases that have diverse sequences and are localized in the ER, nucleus, cytosol, mitochondria and cell membrane. The PDI superfamily has multiple functions including, acting as molecular chaperones, protein-binding partners, and hormone reservoirs. Recently , PDI family members have been implicated in the regulation of apoptotic signaling events. The complexities underlying the molecular mechanisms that define the switch from pro-survival to pro-death response are evidenced by recent studies that reveal the roles of specific chaperone proteins as integration points in signaling pathways that determine cell fate. The following review discusses the dual role of PDI in cell death and survival during ER stress.
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