Generation Of Reactive Oxygen Radicals Research Articles

Abiotic Stress in Rice: Visiting the Physiological Response and Its Tolerance Mechanisms

Rice (Oryza sativa L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in domesticated rice. Ensuring high and constant rice production is vital to facilitating human food supplies, as over three billion people around the globe rely on rice as their primary source of dietary intake. However, the world’s rice production and grain quality have drastically declined in recent years due to the challenges posed by global climate change and abiotic stress-related aspects, especially drought, heat, cold, salt, submergence, and heavy metal toxicity. Rice’s reduced photosynthetic efficiency results from insufficient stomatal conductance and natural damage to thylakoids and chloroplasts brought on by abiotic stressor-induced chlorosis and leaf wilting. Abiotic stress in rice farming can also cause complications with redox homeostasis, membrane peroxidation, lower seed germination, a drop in fresh and dry weight, necrosis, and tissue damage. Frequent stomatal movements, leaf rolling, generation of reactive oxygen radicals (RORs), antioxidant enzymes, induction of stress-responsive enzymes and protein-repair mechanisms, production of osmolytes, development of ion transporters, detoxifications, etc., are recorded as potent morphological, biochemical and physiological responses of rice plants under adverse abiotic stress. To develop cultivars that can withstand multiple abiotic challenges, it is necessary to understand the molecular and physiological mechanisms that contribute to the deterioration of rice quality under multiple abiotic stresses. The present review highlights the strategic defense mechanisms rice plants adopt to combat abiotic stressors that substantially affect the fundamental morphological, biochemical, and physiological mechanisms.

Regeneration Plate 3.0 – Improvement and Maintenance of Intestinal Health by Reduction of Oxidative Stress and Inflammation

Background: Sleep is an integral biological necessity and is understood to possess recuperative and regenerative properties. Sleep deprivation has been associated with diseases and an increase in morbidity and mortality. Several recent studies have suggested a strong relation between insufficient sleep and gastrointestinal diseases, especially when triggered by inflammatory processes. Accordingly to these findings it has been reported that sleep deprivation in both humans and experimental animals causes a progressive increase in circulating white blood cells, mainly neutrophils as well as an increase in various circulating proinflammatory molecules. Experimental: Against this background we used cultured intestinal epithelial cells to investigate the positive impact of a specially designed device, Regeneration Plate 3.0, which is positioned under the bed during sleep and is stated to improve systemic health on the cellular level by reducing oxidative stress which acts on the body. The plate produces a vital field with a frequency pool containing all important regeneration frequencies within a radius of 90 cm. The body's own energy field only resonates with those frequencies that are required for an optimal supply of energy to the cells. The field strength of the vital field is adjusted in such a way that the energy system cannot be over-energized. In addition, we also used an in vitro model with inflammation-mediating cells (= functional neutrophils) to examine whether the Regeneration Plate 3.0 might be able to reduce the generation of reactive oxygen radicals during an inflammatory process. Results: The results demonstrate that the Regeneration Plate 3.0 was able to reduce oxidative stress acting on intestinal epithelial cells. After 24 hours, the percentage of surviving cells after exposure to 2 mM hydrogen peroxide and the Regeneration Plate 3.0 for 8 hours was 27.7 ± 5.7%, while the viability of the untreated control cells was 14.7 ± 2.9% (mean values ± standard deviations). The difference between both experimental groups was statistically highly significant at the p ≤ 0.01 level. Moreover, the generation of superoxide anion radicals by functional neutrophils was reduced by nearly 50% in comparison to untreated control cells. Again, the difference between both groups was statistically highly significant at the p ≤ 0.01 level. Conclusions: Both beneficial effects of the Regeneration Plate 3.0 shown in the present in vitro study can act on the body during sleep and might enhance not only intestinal health, but also systemic health and well-being.

Efficient activation of peroxodisulfate by novel bionic iron-encapsulated biochar: The key roles of electron transfer pathway and reactive oxygen species evolution.

In this study, a novel iron-encapsulated biochar (Fe@BC) was prepared using the biomass cultivated with an iron-containing solution. The iron in Fe@BC showed the phase change from Fe3O4 to α-Fe, and to CFe15.1, with the increase of pyrolysis temperature (500-900°C), and a graphene shell formed on the surface of Fe@BC. In addition, the signals assigned to the π-π*shake up, pyridinic N, graphitic N, and defects of Fe@BC were found to be stronger as the pyrolysis temperature increased. The F4@B9 sample, which was prepared at 900°C, exhibited an excellent performance (98.01%) to activate peroxydisulfate (PDS) for the degradation of 2,4-dichlorophenol. Electron paramagnetic resonanceand chemical quenching experiments revealed that reactive oxygen radicals (ROS) including sulfate radical (•SO4-), hydroxyl radical (•OH), superoxide radical (•O2-), and singlet oxygen (1O2) existed in the F4@B9/PDS system. Furthermore, the micro-electrolysis process facilitated the generation of •O2- (12.35%) and 1O2 (6.49%) compared with the pure PDS system. Density functional theory revealed that, for the F4@B9-activated PDS process, the graphene shell of F4@B9 served as catalytic active sites as well. According to the correlation analysis, the iron specie of CFe15.1 was more favorable for the generation of ROS than α-Fe. Also, π-π*shake up, pyridinic N, graphitic N, and defects participated in the PDS activation. This study provides a new method for the preparation of high-performance catalysts from naturally grown biomass with high iron contents.

Boosting Doxorubicin-Induced Mitochondria Apoptosis for the Monodrug-Mediated Combination of Chemotherapy and Chemodynamic Therapy.

Doxorubicin (Dox)-mediated generation of reactive oxygen radicals (ROS) for mitochondrial apoptosis is identified as a new cytotoxic mechanism in addition to the well-established one via nuclear DNA replication interference. However, this mechanism contributes far less than the latter to Dox therapy. This newly identified pathway to make Dox therapy function like the combination of chemodynamic therapy (CDT) and chemotherapy-mediated by Dox alone would be amplified. One-pot nanoconstruction (HEBD) is fabricated based on the chemical reactions driven assemblies among epigallocatechin gallate (EGCG), buthionine sulfoximine (BSO) and formaldehyde in aqueous mediums followed by Dox adsorption. Acid tumor microenvironments allow the liberation of EGCG, BSO, and Dox due to the breakage of Schiff base bonds. EGCG component in HEBD is responsible for targeting mitochondria and disrupting mitochondrial electron transport chain (mETC) to compel electrons leakage in favor of their capture by Dox to produce more ROS. EGCG-induced mETC disruption results in mitochondrial respiration inhibition with alleviated hypoxia in tumor cells while BSO inhibits glutathione biosynthesis to protect ROS from redox depletion, further boosting Dox-induced CDT. This strategy of amplifying CDT pathway for the Dox-mediated combined therapy could largely improve antitumor effect, extend lifespan of tumor-bearing mice, reduce risks of cardiotoxicity and metastasis.

Multifunctional 3D MoSx/Zn3In2S6 nanoflower for selective photothermal-catalytic biomass oxidative and non-selective organic pollutants degradation

Herein, we report on a 3D MoSx/Zn3In2S6 nanoflower for efficient photocatalytic selective oxidation of benzyl alcohol (BA) to benzaldehyde (BAD) (100 % conversion and 96.18 % selectivity in 1 h) with simultaneous H2 coproduction. The experimental results, in combination with DFT calculations, reveal that MoSx not only endows photothermal properties of the composite but also acts as an electron transport bridge promoting photogenerated charge transfer, which in turn promotes the extraction of Cα-H to produce H2. MoSx/Zn3In2S6 also demonstrated strong ability to selectively oxidize a lignin model compound, 2-phenoxy-1-phenylethanol (PP-ol), to 2-phenoxyacetophenone (PP-one) with H2 coproduction. When incorporated with peroxydisulfate (PDS) for organic pollutant degradation, the MoSx/Zn3In2S6 showed exceptional efficiency with 99.51 % removal of 2-mercaptobenzothiazole (MBT) in 20 min. This is attributed to Mo4+/Mo5+/Mo6+ redox interactions that activate PDS and promote generation of reactive oxygen radicals. This work provides a feasible strategy to design photocatalyst for biomass valorization and organic pollutants degradation.

Synthesis of carbon dots from taurine as bioimaging agent and nanohybrid with ceria for antioxidant and antibacterial applications

Here we have synthesized water soluble and biocompatible carbon dots (CDs) from taurine via thermal decomposition method. The CDs showed nearly spherical shape with diameter less than 10 nm. The CDs exhibited excitation dependent fluorescence emission and could be used for mammalian cell imaging. The CDs showed excellent DPPH and hydrogen peroxide radical scavenging activity in cell free system. Besides, the CDs also displayed significant intracellular radical scavenging activity in human normal kidney epithelial (NKE) cells. Furthermore, nanohybrids consisting of both CDs and nanoceria (CeO2) were prepared and tested for their biomedical applications. The nanohybrids showed significant antioxidant activities in both cell free and intracellular conditions. The CDs and nanohybrids possessed very little toxicity upto the concentration of 100 μg/mL when treated for 24 hours in human NKE cells. The CDs as well as nanohybrids further displayed significant bacterial growth inhibition against both gram-positive and gram-negative bacteria under dark as well as light illumination condition via the bacterial membrane damage. However, under the light illumination, the bacterial growth inhibition of CDs and nanohybrids was further enhanced due to the generation of reactive oxygen radicals and subsequent DNA degradation. A higher dose-dependent intracellular antioxidant and antibacterial activities of the nanohybrid is attributed to the synergistic effect of nanoceria and CDs. All these results clearly reflected that our synthesized CDs and their nanohybrids can be used for several biomedical applications.

The protective effects of topiramate on intestinal injury induced with infrarenal aortic occlusion via oxidative stress and apoptosis

ABSTRACT Purpose: Prolonged surgical procedures and some clinical conditions such as surgeries of thoracoabdominal aorta, mesenteric ischemia, cardiopulmonary bypass, strangulated hernias and neonatal necrotizing enterocolitis may cause decreased perfusion and injury of relevant organs and tissues. After reperfusion, injuries may get worse, leading to ischemia–reperfusion (I/R) injury. Reperfusion following arterial clamping allows oxygen to ischemic tissues and produce injury by multiple mechanisms, including neutrophilic infiltration, intracellular adhesion molecules, and generation of reactive oxygen radicals. In this study with the analysis of SOD, MDA and Caspase-3 levels, we aimed to investigate the effect of topiramate on the outcome of I/R occured after abdominal aorta clamping on rats. Materials and Methods: Totaly 24 Sprague–Dawley male rats were randomly divided into three experimental groups; the control group (n = 8), I/R (n = 8) and I/R+ topiramate (n = 8). Topiramate (100 mg/kg/day); 50 mg/kg (single dose) was administered intraperitoneally after being diluted with saline 5 days before I/R. Results: The intestinal tissue of the ischemia group displayed hemorrhage, Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields as a result of aortic occlusion. We also observed that MDA levels and Caspase-3 positivity increased and SOD levels decreased in the small intestine. However, topiramate administration decreased Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields, Caspase-3 positivity, and MDA levels. Conclusion: Our findings suggest that topiramate is effective against aortic occlusion-induced intestinal injury by reducing oxidative stress and apoptosis.

Nanosilver Targets the Bacterial Cell Envelope: The Link with Generation of Reactive Oxygen Radicals.

The work describes the interactions of nanosilver (NAg) with bacterial cell envelope components at a molecular level and how this associates with the reactive oxygen species (ROS)-mediated toxicity of the nanoparticle. Major structural changes were detected in cell envelope biomolecules as a result of damages in functional moieties, such as the saccharides, amides, and phosphodiesters. NAg exposure disintegrates the glycan backbone in the major cell wall component peptidoglycan, causes complete breakdown of lipoteichoic acid, and disrupts the phosphate-amine and fatty acid groups in phosphatidylethanolamine, a membrane phospholipid. Consistent with the oxidative attacks, we propose that the observed cell envelope damages are inflicted, at least in part, by the reactive oxygen radicals being generated by the nanoparticle during its leaching process, abiotically, without cells. The cell envelope targeting, especially those on the inner membrane phospholipid, is likely to then trigger the rapid generation of lethal levels of cellular superoxide (O2•-) and hydroxyl (OH•) radicals herein seen with a model bacterium. The present study provides a better understanding of the antibacterial mechanisms of NAg, whereby ROS generation could be both the cause and consequence of the toxicity, associated with the initial cell envelope targeting by the nanoparticle.

Biochemical Mechanism of Rhododendrol-Induced Leukoderma.

RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce leukoderma in some consumers. We have examined the biochemical basis of the RD-induced leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products. Subsequently, we confirmed that human tyrosinase is able to oxidize both enantiomers of RD. We then showed that B16 cells exposed to RD produce high levels of RD-pheomelanin and protein-SH adducts of RD-quinone. Our recent studies showed that RD-eumelanin—an oxidation product of RD—exhibits a potent pro-oxidant activity that is enhanced by ultraviolet-A radiation. In this review, we summarize our biochemical findings on the tyrosinase-dependent metabolism of RD and related studies by other research groups. The results suggest two major mechanisms of cytotoxicity to melanocytes. One is the cytotoxicity of RD-quinone through binding with sulfhydryl proteins that leads to the inactivation of sulfhydryl enzymes and protein denaturation that leads to endoplasmic reticulum stress. The other mechanism is the pro-oxidant activity of RD-derived melanins that leads to oxidative stress resulting from the depletion of antioxidants and the generation of reactive oxygen radicals.

Clinical manifestations and basic mechanisms of myocardial ischemia/reperfusion injury.

Acute myocardial ischemia/reperfusion (I/R) injury is a significant, unsolved clinical puzzle. In the disease context of acute myocardial infarction, reperfusion remains the only effective strategy to salvage ischemic myocardium, but it also causes additional damage. Myocardial I/R injury is composed of four types of damage, and these events attenuate the benefits of reperfusion therapy. Thus, inventing new strategies to conquer I/R injury is an unmet clinical need. A variety of pathological processes and mediators, including changes in the pH, generation of reactive oxygen radicals, and intracellular calcium overload, are proposed to be crucial in I/R-related cell injury. Among the intracellular events that occur during I/R, we stress the importance of protein phosphorylation signaling and elaborate its regulation. A variety of protein kinase pathways could be activated in I/R, including reperfusion injury salvage kinase and survivor-activating factor enhancement pathways, which are critical to cardiomyocyte survival. In addition to serine/threonine phosphorylation signaling, protein tyrosine phosphorylation is also critical in multiple cell functions and survival. However, the roles of protein kinases and phosphatases in I/R have not been extensively studied yet. By better understanding the mechanisms of I/R injury, we may have a better chance to develop new strategies for I/R injury and apply them in the clinical patient care.

Neuroprotective effect of Spirulina in cerebral ischemia–reperfusion injury in rats

Epidemiological studies indicate that the intake of Mediterranean-style diet is inversely associated with risk of stroke, cardiovascular diseases, and cancer. Spirulina is widely used nutritional supplement rich in proteins and antioxidants. Evidence demonstrates that the impaired energy metabolism and the excessive generation of reactive oxygen radicals contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effect of Spirulina was investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male albino rats were divided into six groups: control, sham-operated group, ischemic control group, and Spirulina-pretreated groups (45, 90 and 180 mg/kg/p.o.). Spirulina was administered once a day, for 7 days. The rats were subjected to a 2-h right MCAO via the intraluminal filament technique and 22 h of reperfusion. Pretreatment with Spirulina significantly reduced the histological changes and neurological deficits. Spirulina at a dose of 180 mg/kg significantly reversed the elevated brain malondialdehyde (MDA) content and restored the decreased activities of brain superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) indicating that Spirulina has the protective potential against cerebral ischemia injury and its protective effects may be due to its antioxidant property.

Transcriptional profiling of mouse liver in response to chronic heat stress

Mice were used to study the effects of chronic heat stress on hepatic gene expression. Twenty-five mice were allocated to either chronic heat stress (34 °C) or control (24 °C) conditions for a period of 2 weeks from 47 to 60 d of age. Nineteen genes differentially expressed in liver were identified using DNA microarrays. Genes involved in the anti-oxidant pathway and metabolism were up-regulated. Genes involved in generation of reactive oxygen radicals and mitochondrial expressed genes were down-regulated. Enzyme activity measurements confirmed the array results. Mice exposed to chronic heat stress showed signs of increased oxidative stress in liver cells.

Development and evaluation of a particle-bound reactive oxygen species generator

Identifying the most important sources and variability of source impact for particulate matter is essential to assessing their health impacts. A central hypothetical mechanism of how particles affect human health involves the generation of reactive oxygen radicals at target sites in situ. These could be generated via activation of cells by cell–particle interactions and by oxidative species present in particulate matter. However, prior studies have shown that there are reactive oxygen species (ROS) associated with ambient respirable particles. In order to assess the health effects of particle-bound oxidative species, a generator was developed to produce ROS-bearing model particles and deliver known, reproducible, and stable exposures to these model particles that could be used in toxicological studies. The generator was found to be capable of providing a stable throughput of these particles with an average ROS generation capability of 6.5 nmol of equivalent H 2 O 2 / m 3 of ( aerosol + ozone ) flow sampled. The development, characterization, and evaluation of the ROS-bearing particle generator is described.

Rosiglitazone, a PPAR-γ ligand, protects against burn-induced oxidative injury of remote organs

Severe burn induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis, as well as generation of reactive oxygen radicals and lipid peroxidation, leading to multiple organ failure. In the present study, we investigated whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligand is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats were exposed to 90 °C (burn group) or 25 °C (control group) water bath for 10 s. Rosiglitazone (4 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn. Rats were decapitated 24 h after injury and the tissue samples from lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and creatinine, blood urea concentrations (BUN) were determined to assess liver and kidney function, respectively. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and lactate dehydrogenase (LDH) were also assayed. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH, IL-1β and TNF-α were elevated in the burn group as compared to the control group. Rosiglitazone treatment reversed all these biochemical indices. According to the findings of the present study, rosiglitazone possesses a anti-inflammatory effect that prevents burn-induced damage in remote organs and protects against organ damage.

Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats

Epidemiological studies indicate that the intake of flavonoids is inversely associated with risk of stroke, cardiovascular diseases and cancer. Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet, anti-tumor, anti-allergic, antiviral activities and estrogenic properties. However, there is no report on the effects of ISL in cerebral ischemia. Evidence demonstrate that the impaired energy metabolism and the excessive generation of reactive oxygen radicals (ROS) contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effects of ISL were investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia–reperfusion injury in rats. Male Sprague–Dawley rats were divided into five groups: sham-operated group, vehicle-pretreated group, and three ISL-pretreated groups (5, 10 and 20 mg kg −1, i.g.). ISL were administered once a day, for 7 days prior to ischemia. The rats were subjected to 2 h right MCAO via the intraluminal filament technique and 22 h reperfusion. Pretreatment with ISL significantly reduced the cerebral infarct volume and edema and produced significant reduction in neurological deficits. In this study, in order to clarify the mechanism of ISL's protection against cerebral ischemia damage, cerebral energy metabolism, brain Na +K +ATPase activity, malondialdehyde (MDA) content and antioxidant enzyme activities were measured. ISL pretreatment increased the brain ATP content, energy charge (EC) and total adenine nucleotides (TAN) in a dose-dependent manner. The brain Na +K +ATPase activity was protected significantly by pretreatment of ISL for 7 days. Pretreatment with ISL significantly inhibited the increases of brain MDA content and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) from declines caused by cerebral ischemia–reperfusion. All these findings indicate that ISL has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property.

β-glucan protects against burn-induced oxidative organ damage in rats

Thermal injury may lead to systemic inflammatory response, and multiple organ failure. Generation of reactive oxygen radicals and lipid peroxidation play important roles in burn-induced remote organ injury. In the present study, we investigated the putative protective effect of local or systemic β-glucan treatment on burn-induced remote organ injury. Wistar albino rats were exposed to 90 °C bath for 10 s to induce thermal trauma. β-glucan (3.75 mg/rat locally or 50 mg/kg orally) or saline was administered immediately after the trauma and were repeated twice daily in 48 h groups. Rats were decapitated either 6 or 48 h after burn injury and the skin, lung, liver, ileum and kidney tissues were taken for the measurement of malondialdehyde (MDA) — an index of lipid peroxidation — and glutathione (GSH) — a key antioxidant — levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase (MPO) activity, while the tumor necrosis factor-α (TNF-α) levels were measured in serum samples. Skin tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decreases in GSH levels of the liver and intestinal tissues (p<0.01–<0.001), while MDA levels were significantly (p<0.01–p<0.001) increased at post-burn 6 and 48 h. Both local and systemic β-glucan treatments significantly reversed (p<0.01–p<0.001) the elevations in MDA levels, while reduced GSH levels were reversed back to control levels (p<0.01–p<0.001); and the raised MPO levels were significantly decreased (p<0.05–p<0.001). The results indicate that both systemic and local administration of β-glucan were effective against burn-induced oxidative tissue damage in the rat. β-glucans, besides their immunomodulatory effects, have additional antioxidant properties. Therefore, β-glucans merit consideration as therapeutic agents in the treatment of burn injuries.

Redox active plasma iron in C282Y/C282Y hemochromatosis

AbstractLabile plasma iron (LPI) represents the redox active component of non–transferrin-bound iron (NTBI). Its presence in thalassemic patients has been recently reported. The aim of the present study was to quantify LPI in HFE genetic hemochromatosis (GH) and to characterize the mechanisms accounting for its appearance. We studied 159 subjects subdivided into the following groups: (1) 23 with iron overloaded GH; (2) 14 with iron-depleted GH; (3) 26 with dysmetabolic hepatosiderosis; (4) 33 with alcoholic cirrhosis; (5) 63 healthy controls. Both NTBI and LPI were substantially higher in patients with iron-overloaded GH than in those with iron-depleted GH or in healthy controls. LPI was significantly correlated with serum transaminase increase in this group. LPI was elevated in the alcoholic cirrhosis subgroup of severely affected patients. LPI was found essentially when transferrin saturation exceeded 75%, regardless of the etiologic condition. Transferrin saturation above 75% was related to iron overload in GH and to liver failure in alcoholic cirrhosis. LPI is present in C282Y/C282Y hemochromatosis and may be a marker of toxicity due to its potential for catalyzing the generation of reactive oxygen radicals in vivo.

Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs

Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 °C (burn group) or 25 °C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-α, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.

Reactive oxygen species in tumor progression

The generation of reactive oxygen radicals in mammalian cells profoundly affects numerous critical cellular functions, and the absence of efficient cellular detoxification mechanisms which remove these radicals can result in several human diseases. Growing evidence suggests that reactive oxygen species (ROS) within cells act as second messengers in intracellular signaling cascades which induce and maintain the oncogenic phenotype of cancer cells. ROS are tumorigenic by virtue of their ability to increase cell proliferation, survival, cellular migration, and also by inducing DNA damage leading to genetic lesions that initiate tumorigenicity and sustain subsequent tumor progression. However, it is also known that ROS can induce cellular senescence and cell death and can therefore function as anti-tumorigenic agents. Therefore, the mechanisms by which cells respond to reactive oxygen species depends on the molecular background of cell and tissues, the location of ROS production and the concentration of individual ROS species. Carcinoma cells produce ROS at elevated rates in vitro, and in vivo many tumors appear persistent to oxidative stress. Thus, the finding that a diet rich in antioxidants or the elimination of ROS by antioxidant compounds prevents the development of certain cancers provided the setting for subsequent investigation of the tumorigenic actions of reactive oxygen species. This review outlines the current knowledge on the various roles of ROS in tumor development and progression.

Increased Concentrations of Cell-Free Plasma DNA after Exhaustive Exercise

Physical exercise leads to temporary ischemia in muscles, followed by increased oxygen supply during recovery as a result of reperfusion. It is thought that the sudden influx of oxygen causes a calcium overload in cells, leading to an influx of inflammatory cells into reperfused tissue. This leads to the generation of reactive oxygen radicals and subsequent oxidative damage to DNA, proteins, and lipids. For example, increased oxidant production in the mitochondria of muscles during acute exercise, followed by reoxygenation, was shown to cause cellular damage (1). In addition, exercise may cause transient muscle damage, characterized by muscle soreness, muscle fiber disarrangement, muscle protein release into plasma, an acute immune response, and decreased muscle performance (2). Regional ATP depletion during reperfusion, disruptions in calcium homeostasis, and the presence of oxygen free radicals have all been implicated in the etiology of muscle fiber damage and necrosis. Furthermore, postexercise lymphocytopenia (2) is well documented and attributed to the exit of lymphocytes from the vascular compartment (3). Other studies have reported exercise-induced DNA damage in leukocytes and raised the question of a possible link to apoptosis (3). This effect is thought to be caused by reactive oxygen species, which are released from peripheral monocytes. The aim of this study was to investigate the effects of physical activity, in particular muscle damage and oxidative stress, during and after a half-marathon race and the subsequent recovery period; we also wanted to measure whether oxidative stress attributable to reoxygenation may be a relevant factor in cellular damage. Cell-free plasma DNA concentrations were used as a sensitive tool for quantification of cellular damage and compared with the conventional measurements of myoglobin and uric acid in blood samples. In this study, blood samples from half-marathon runners were taken before the race, immediately after the race, and 2 h …