Pro-oxidant Factors Research Articles

Biochemical markers of oxidative stress in patients with inflammatory bowel diseases

Introduction: Inflammatory bowel disease (IBD) is a group of diseases of unexplained aetiology, characterized by periods of remissions and exacerbations. Reactive oxygen species (ROS) as far as disorders of balance between levels of prooxidants and antioxidants may also participate in the occurrence of IBD. The aim of the present study was an assessment of the antioxidative barrier of the organism in patients with inflammatory bowel disease. Material and methods: The study group consisted of 99 patients (80 with IBD as a study group and 19 healthy as a control group) from Jan Biziel University Hospital in Bydgoszcz, Poland. Venous blood was the material for biochemical analysis: HT, GSH, GPXp, GPXRBC, GST, GR, SOD-1, MDA, NO2-/NO3- and CP. Results: There were statistically significant differences in oxidative stress parameters observed between the study group and the control group, especially concerning HT, GSH, GPXRBC, GST, SOD-1, MDA and NO2-/NO3-. Discussion: The assumption that increased activity of antioxidative compounds may constitute a defence against the influence of oxidative stress may be true. Their decreased activity may participate in lowering an organism’s abilities to defend against oxidative stress and cause the development of free radical diseases. Further studies into targeted preventive strategies are needed. Conclusions: Prooxidative factors play an essential role in the pathogenesis of IBD. Due to the still unknown etiopathology of IBD, research on imbalances between pro-oxidants and antioxidants should be continued in larger groups of patients.

Effect of temperature changes on antioxidant enzymes and oxidative stress in gastropod Nerita oryzarum collected along India's first Tarapur Atomic Power Plant site

Temperature can be considered as pro-oxidant factor that favor the generation of ROS on the species with lower antioxidant efficiency may leads to affect the level of tolerance. So the basic antioxidant enzyme activity (LPO, CAT, SOD, GPx and GST) of gastropod Nerita oryzarum was evaluated at six stations which located between the thermal effluent discharges points from Tarapur Atomic Power Station, India. The antioxidant enzyme activity was shown that all enzyme at discharge point (SII station) where the maximum temperature of heated effluent released. The average maximum values of enzyme activity recorded for LPO, CAT, SOD, GPx and GST were 1.88 ± 0.12, 1.52 ± 0.14, 22.57 ± 0.89, 1.98 ± 0.2 and 17.22 ± 0.63 respectively. The results were inferred the level water temperature directly proportional to the oxidative stress by ROS generation in Nerita oryzarum. Similar results were observed at laboratory experiment under the condition i.e., Treatment 1 (300C), Treatment 2 (350C), Treatment 3 (400C) and Control (250C). The present prima facie work clearly indicated the physiological response of N. oryzarum with respect to antioxidant enzyme activity against the heated effluent released, which will be useful as baseline information for future research work.

Resveratrol improved kidney function and structure in malignantly hypertensive rats by restoration of antioxidant capacity and nitric oxide bioavailability

The main cause of death among patients with malignant hypertension is a kidney failure. The promising field in essential and malignant hypertension therapy could be centered on the amelioration of oxidative stress using antioxidant molecules like resveratrol. Resveratrol is a potent antioxidative agent naturally occurred in many plants that possess health-promoting properties. In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with anti-oxidative activity, in NG-L-Arginine Methyl Ester (L-NAME) treated spontaneously hypertensive rats (SHR) - malignantly hypertensive rats (MHR). Resveratrol significantly improves oxidative damages by modulation of antioxidant enzymes and suppression of prooxidant factors in the kidney tissue of MHR. Enhanced antioxidant defense in the kidney improves renal function and ameliorates the morphological changes in this target organ. Besides, protective properties of resveratrol are followed by the restoration of the nitrogen oxide (NO) pathway. 4) Conclusion: Antioxidant therapy with resveratrol could represent promising therapeutical approach in hypertension, especially malignant, against kidney damage.

Changes in Spermatogenesis, Lipoperoxidation Processes, and Antioxidant Protection in Men with Pathozoospermia after COVID-19. The Effectiveness of Correction with a Promising Antioxidant Complex.

The indicators of spermatogenesis and the state of LPO and antioxidant protection in men with pathozoospermia after COVID-19 were assessed before and after treatment an antioxidant complex. Blood plasma served as the material for biochemical studies. In the examined patients, the parameters of spermatogenesis, as well as blood concentration of LPO components (diene conjugates and TBA-reactive substances) were analyzed. The total antioxidant activity of the blood was determined as an indicator characterizing the total activity of LPO inhibitors and determining its buffer capacity. In patients recovered from COVID-19, an increase in spermatogenesis disorders and shifts towards the predominance of prooxidant factors were observed. After a course (1 month) of antioxidant complex, patients showed increased sperm motility, decreased leukocyte count in the ejaculate, and restored balance in the prooxidant—antioxidant system towards antioxidant components. The effectiveness of correction of post-COVID disorders largely depends on the degree of damage to the structure and function of cell membranes caused by oxidative stress. The use of the antioxidant complex is a promising option, because it reduces the level of LPO, enhances antioxidant protection of the body, and also normalizes some parameters of spermatogenesis.

Oxidative stress, biochemical, and histopathological changes associated with acute lumpy skin disease in cattle.

Background and Aim:Lumpy skin disease (LSD) is a highly infectious endemic viral disease of cattle in Africa and the Middle East. The objectives of this study were to assess histopathological changes in cattle infected with LSD and measure serum malondialdehyde (MDA – oxidant) and total anti-oxidant capacity (TAC – anti-oxidant), trace elements (zinc, copper, and iron), cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha [TNF-α]), haptoglobin (Hp), serum amyloid A (SAA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), blood urea nitrogen (BUN), and creatinine concentrations.Materials and Methods:Blood samples were collected from a total of sixty native and mixed breed cattle; (healthy; n = 25) and (LSD diseased; n = 35). Serum concentrations of MDA and TAC were measured by colorimetric methods. Serum IL-1β, IL-6, IL-10, TNF-α, Hp, and SAA concentrations were determined using human-specific enzyme-linked immunoassay kits.Results:Serum MDA, cytokine (IL-1β, IL-6, and TNF-α), Hp, SAA, AST, ALT, CPK, BUN, and creatinine concentrations were significantly higher, while TAC, IL-10, zinc, copper, and iron concentrations were significantly lower in LSD compared to healthy cattle (p < 0.05). Cows and exotic mixed breed cattle were at higher risk of LSD oxidative stress than bulls and local breeds (p < 0.05). Age was not associated with the risk of LSD (p > 0.05). Histologically, there was extensive tissue necrosis, severe vasculitis, mononuclear cell infiltration, and intracytoplasmic inclusion bodies.Conclusion:LSD is associated with pro-oxidative and pro-inflammatory states from imbalances that favor pro-oxidant and pro-inflammatory factors in the detriment of anti-oxidant and anti-inflammatory factors, leading to organ dysfunction and ultimately death. Oxidative stress is more frequent in cows and mixed breed cattle than in bulls and local breeds.

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin.

Biocompatibility in hemodialysis (HD) has considerably improved in recent decades, but remains an open issue to be solved, appearing essential to reduce systemic inflammation and enhance patients’ clinical outcomes. Clotting prevention, reduction in complement and leukocyte activation, and improvement of antioxidant effect represent the main goals. This review aims to analyze the different pathways involved in HD patients, leading to immune system dysfunction and inflammation. In particular, we mostly review the evidence about thrombogenicity, which probably represents the most important characteristic of bio-incompatibility. Platelet activation is one of the first steps occurring in HD patients, determining several events causing chronic sub-clinical inflammation and immune dysfunction involvement. Moreover, oxidative stress processes, resulting from a loss of balance between pro-oxidant factors and antioxidant mechanisms, have been described, highlighting the link with inflammation. We updated both innate and acquired immune system dysfunctions and their close link with uremic toxins occurring in HD patients, with several consequences leading to increased mortality. The elucidation of the role of immune dysfunction and inflammation in HD patients would enhance not only the understanding of disease physiopathology, but also has the potential to provide new insights into the development of therapeutic strategies.

Oxidative Stress Intensity in Children and Adolescents with a New Coronavirus Infection

The aim of our research was to assess the intensity of oxidative stress (OS) in children and adolescents with COVID-19 using the oxidative stress index (OSI). Methods and Results: The study was conducted between May 2020 and March 2021. The main group included 17 children and adolescents [8(47.1%) boys and 9(52.9%) girls; mean age of 12.35±4.01 years] with diagnosed COVID-19 infection (mild to moderate course) selected as a result of the primary diagnostic examination from among those admitted to hospitalization at the Irkutsk Regional Infectious Diseases Clinical Hospital. The control group included 17 healthy children and adolescents (average age of 12.35±4.01 years) matched by copy-pair type. The obtained data indicated statistically significant differences in a number of parameters between children and adolescents with COVID-19 and the control groups. We found statistically significant higher levels of LPO products (CDs, P&lt;0.0001; KD and CT, P=0.006; and TBARs, P=0.013) in the study group than in the control group. Among AOD system parameters, the levels of retinol (P=0.015) and reduced glutathione (P=0.048) and SOD activity (P&lt;0.0001) were statistically lower in the study group than in the control group. The OSI level was significantly greater (by 8.5 times, P=0.028) in the study group than in the control group, which confirms the development of antioxidant deficiency in COVID-19. Conclusion: The results of the assessment of OSI in children and adolescents with COVID-19 indicate insufficient activity of some critical components of AOD and a shift of the redox balance toward pro-oxidant factors, which can have extremely negative consequences in the development of the disease. In this regard, we recommend carrying out corrective measures to stabilize LPO/AOD parameters by including drugs with antioxidant properties in the treatment complex.

Dynamics of the lipoperoxidation process in the oral fluid of patients with chronic generalized periodontitis with the complex application of laser therapy and interval hypoxic training

The performed research is devoted to the study of lipid peroxidation processes in patients with chronic generalized periodontitis under the conditions of the course application of infrared laser therapy and normobaric interval hypoxic training. The results of the study allow us to conclude that the development of inflammatory destructive processes in periodontal tissues closely correlates with manifestations of oxidative stress, which develops as a result of an imbalance in the pro-oxidants-antioxidants system. Supplementing the standard therapy of chronic generalized periodontitis with the course use of physiotherapeutic factors in the mono-influence mode is accompanied by an increase in the potential of the antioxidant protection of the oral cavity. The complex use of physiofactors contributes to an increase in the activity of the antioxidant system, realized through the mechanisms of functional potentiation. The close relationship revealed between lipid peroxidation products and index characteristics of dental status, reflecting the pathogenetic role of pro-oxidant factors in the development of chronic generalized periodontitis, allows us to consider biomarkers of peroxide metabolism and the antioxidant protection coefficient as criteria for the effectiveness of the treatment.

The Effects of TNF-α Inhibition on the Metabolism of Cartilage: Relationship between KS, HA, HAPLN1 and ADAMTS4, ADAMTS5, TOS and TGF-β1 Plasma Concentrations in Patients with Juvenile Idiopathic Arthritis.

We assessed the effect of 24-month anti-tumor necrosis factor alpha (TNF-α) treatment on the remodeling of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: Quantitative evaluation of keratan sulfate (KS), hyaluronic acid (HA), hyaluronan and proteoglycan link protein 1 (HAPLN1), as potential biomarkers of joint dysfunction, and the levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5, total oxidative status (TOS) and transforming growth factor (TGF-β1) was performed (using immunoenzymatic methods) in blood obtained from patients before and after 24 months of etanercept (ETA) treatment. Results: When compared to the controls, KS, HA and HAPLN1 levels were significantly higher in patients with an aggressive course of JIA qualified for ETA treatment. An anti-cytokine therapy leading to clinical improvement promotes the normalization only of the HA level. Proteolytic and pro-oxidative factors, present in high concentrations in patients before the treatment, correlated with HAPLN1, but not with KS and HA levels. In these patients, negative correlations were found between the levels of TGF-β1 and KS, HA and HAPLN1. Conclusion: The anti-TNF-α therapy used in patients with JIA has a beneficial effect on ECM cartilage metabolism, but it does not completely regenerate it. The changes in the plasma HA level during the anti-cytokine therapy suggest its potential diagnostic utility in monitoring of disease activity and may be used to assess the efficacy of ETA treatment.

Flavonoids: The Innocuous Agents Offering Protection against Alzheimer's Disease Through Modulation of Proinflammatory and Apoptotic Pathways.

Beginning from mild cognitive impairment in patients suffering from Alzheimer's disease (AD), dementia sets in with the progress of the disease. The pathological changes in the brain begin fifteen to twenty years before AD related dementia develops. Presence of senile plaques and neurofibrillary tangles are considered the hallmarks of AD brain. Chronic inflammation resulting from the disruption of the equilibrium between anti-inflammatory and pro-inflammatory signalling emerges as another important feature of AD and also other neurodegenerative diseases. Substantial studies demonstrate that this sustained immune response in the brain is associated with neuronal loss, along with facilitation and aggravation of Aβ and NFT pathologies. Although it is well accepted that neuroinflammation and oxidative stress have both detrimental and beneficial influences on the brain tissues, the involvement of microglia and astrocytes in the onset and progress of the neurodegenerative process in AD is becoming increasingly recognized. Although the cause of neuronal loss is known to be apoptosis, the mechanism of promotion of neuronal death remains undisclosed. Controlling the activation of the resident immune cells and/or the excessive production of pro-inflammatory and pro-oxidant factors could be effective as therapeutics. Among the phytonutrients, the neuroprotective role of flavonoids is beyond doubt. This review is an exploration of the literature on the role of flavonoids in these aspects. Flavonoids are not only effective in ameliorating the adverse consequences of oxidative stress but also impede the development of late onset Alzheimer's disease by modulating affected signalling pathways and boosting signalling crosstalk.

Oxidative Balance Scores (OBSs) Integrating Nutrient, Food and Lifestyle Dimensions: Development of the NutrientL-OBS and FoodL-OBS.

Oxidative Balance Scores (OBS) are tools that allow us to assess the individual’s antioxidant state by ranking both antioxidant and pro-oxidant components of dietary and lifestyle factors. Our aim was to develop novel OBSs accounting for either the global supply of nutrient antioxidants in the diet, or the intake of antioxidant-rich foods, in combination with lifestyle factors. Pro-oxidant factors were also considered. Within two centers of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) study, EPIC-Granada and EPIC-Gipuzkoa (N = 14,756 participants), we developed the Nurient, Food and Lifestyle OBS (NutrientL-OBS and FoodL-OBS), and their simplified versions (solely with dietary or lifestyle factors, the Nutrient-OBS, Food-OBS and L-OBS). Their antioxidant potential was evaluated considering their relationship with: (i) 20 scores of adherence to the Mediterranean Diet (MD); and, (ii) 25 biomarkers of antioxidant nutrients (ascorbic acid, β-carotene, etc.), inflammation (CRP, TNF-alpha, etc.) and oxidative stress (uric acid), among 210 participants. Spearman correlation and multivariate linear regression analyses were applied to analyze these associations. Some statistically significant relationships were encountered between the NutrientL-OBS and the FoodL-OBS with the MD scores, and with ascorbic acid (per one-unit increase in OBS: β = 0.012 and 0.015; p = 0.022 and 0.008, respectively) and CRP (per one-unit increase in both OBS: β = −0.02; p = 0.02); the latter appeared to be restricted to the OBS´s lifestyle components. In conclusion, the NutrientL- and FoodL-OBSs and their sub-versions are related to antioxidant-rich dietary patterns and to biomarkers of antioxidant nutrient intake and inflammation, supporting that these tools are valid to assess the individual´s oxidative/antioxidant status.

Mechanistic understanding of metal-catalyzed oxidation of polysorbate 80 and monoclonal antibody in biotherapeutic formulations

Surfactants are commonly used in biotherapeutic formulations to prevent the formation of aggregates and protect proteins from denaturation. Among them polysorbates are the most widely used. However, they are known to be prone to degradation, mainly via enzymatic hydrolysis and oxidation.In this study, the impact of different conditions and factors on the oxidation of polysorbate 80 (PS80) and of a monoclonal antibody (mAb) was evaluated. In particular, the role of different formulation components (e.g., mAb concentration, pH, buffer, surfactant grade, chelators) was investigated in the presence of iron as transition metal contaminant.The results of our studies demonstrated that PS80 oxidation was accelerated even in the presence of iron levels as low as 20 ppb. In addition, the results showed that the oxidation of a specific solvent-exposed mAb methionine increased with PS80 oxidation, in particular under accelerated stress conditions and that the oxidation phenomenon was hindered in absence of iron or after addition of EDTA. Our results showed that PS80 “all oleate” (PS80-AO) was more sensitive to oxidative degradation than PS80 “multi-compendial” (PS80-MC). Contrary to acetate and citrate buffers, the results showed that the kinetics of PS80 oxidation was pH-dependent in presence of histidine buffer. It was also demonstrated that, when increasing its concentration, the mAb exhibited a protective effect against metal catalyzed PS80 and methionine oxidation.Our systematic studies on the role of the formulation components and potential contaminants (i.e., iron) demonstrated the complexity of the oxidative mechanism and the importance of different competitive systems, including pro-oxidant factors (e.g., iron, pH, PS80 quality) and antioxidant factors (e.g., protein concentration, EDTA, citrate) that may occur in biologic formulations containing PS80.

Adverse renal effects of NLRP3 inflammasome inhibition by MCC950 in an interventional model of diabetic kidney disease.

Activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome has been reported in diabetic complications including diabetic kidney disease (DKD). However, it remains unknown if NLRP3 inhibition is renoprotective in a clinically relevant interventional approach with established DKD. We therefore examined the effect of the NLRP3-specific inhibitor MCC950 in streptozotocin-induced diabetic mice to measure the impact of NLRP3 inhibition on renal inflammation and associated pathology in DKD. We identified an adverse effect of MCC950 on renal pathology in diabetic animals. Indeed, MCC950-treated diabetic animals showed increased renal inflammation and macrophage infiltration in association with enhanced oxidative stress as well as increased mesangial expansion and glomerulosclerosis when compared with vehicle-treated diabetic animals. Inhibition of the inflammasome by MCC950 in diabetic mice led to renal up-regulation of markers of inflammation (Il1β, Il18 and Mcp1), fibrosis (Col1, Col4, Fn1, α-SMA, Ctgf and Tgfβ1) and oxidative stress (Nox2, Nox4 and nitrotyrosine). In addition, enhanced glomerular accumulation of pro-inflammatory CD68 positive cells and pro-oxidant factor nitrotyrosine was identified in the MCC950-treated diabetic compared with vehicle-treated diabetic animals. Collectively, in this interventional model of established DKD, NLRP3 inhibition with MCC950 did not show renoprotective effects in diabetic mice. On the contrary, diabetic mice treated with MCC950 exhibited adverse renal effects particularly enhanced renal inflammation and injury including mesangial expansion and glomerulosclerosis.

Levels of Serum Selenium and Zinc in Critically ill Type 2 Diabetics and Normal Healthy Individuals at Tertiary Care Hospital, Surat, India

Introduction: Type 2 Diabetes Mellitus (T2DM), accounting for 85-90% of diabetic subjects globally, is reported to be also caused by imbalance between pro-oxidant and antioxidant factors. This very fact necessitates exploring and evaluating the possibilities of role of various antioxidant trace elements like selenium and zinc, in further understanding the pathogenesis and appropriate applicable intervention required, if any for patients suffering from diabetes mellitus. The levels of trace elements like selenium and zinc, representing antioxidant capacity, might be implicated in development of type II diabetes and vice versa. Aim: To evaluate the levels of serum selenium and zinc in critically ill type 2 diabetic patients and comparing them with healthy individuals. Materials and Methods: This case-control study was conducted for a period of nine months from October 2016 to June 2017. Fifty critically ill type 2 diabetic patients and 150 apparently healthy age and gender matched controls were recruited into this study. Serum selenium and zinc levels were estimated in subjects of both the groups. Mean, standard deviation, Analysis of Variance (ANOVA) test and student t-test were statistical tools used to interpret the results. Results: Fifty critically ill T2DM patients constituted the cases and 150 age and sex matched healthy adults were in the control group. Mean Random Blood Sugar (RBS) in controls was 113.14±25.52 mg/dL while in that in cases was 246.48±98 mg/dL and the difference was significant (p-value &lt;0.01). This study showed significant difference (p&lt;0.01) in the level of serum selenium and zinc levels in critically ill diabetic patients compared to healthy individuals across all age groups i.e., &lt;40, 40 to 55 and &gt;55 years. The mean level of selenium in cases and controls were 83.8±11.97 and 103.08±67.7 μg/dL (p-value &lt;0.01) respectively. The mean level of zinc amongst cases and controls were 40.83±21.19 and 103.08±67.7 (p-value &lt;0.01), respectively. Conclusion: Serum selenium and zinc levels were decreased in critically ill type 2 diabetic patients owing to the increased production of free radicals in them. Supplementation of selenium and zinc in these individuals could be beneficial and is therefore recommended.

Tissue-Specific Gamma-Flicker Light Noninvasively Ameliorates Retinal Aging.

Aging is a risk factor for multiple retinal degeneration diseases. Entraining brain gamma oscillations with gamma-flicker light (γFL) has been confirmed to coordinate pathological changes in several Alzheimer's disease mouse models and aged mice. However, the direct effect of γFL on retinal aging remains unknown. We assessed retinal senescence-associated beta-galactosidase (β-gal) and autofluorescence in 20-month-old mice and found reduced β-gal-positive cells in the inner retina and diminished lipofuscin accumulation around retinal vessels after 6 days of γFL. In immunofluorescence, γFL was further demonstrated to ameliorate aging-related retinal changes, including a decline in microtubule-associated protein 1 light chain 3 beta expression, an increase in complement C3 activity, and an imbalance between the anti-oxidant factor catalase and pro-oxidant factor carboxymethyl lysine. Moreover, we found that γFL can increase the expression of activating transcription factor 4 (ATF4) in the inner retina, while revealing a decrease of ATF4 expression in the inner retina and positive expression in the outer segment of photoreceptor and RPE layer for aged mice. Western blotting was then used to confirm the immunofluorescence results. After mRNA sequencing (NCBI Sequence Read Archive database: PRJNA748184), we found several main mechanistic clues, including mitochondrial function and chaperone-mediated protein folding. Furthermore, we extended γFL to aged Apoe-/- mice and showed that 1-m γFL treatment even improved the structures of retinal-pigment-epithelium basal infolding and Bruch's membrane. Overall, γFL can orchestrate various pathological characteristics of retinal aging in mice and might be a noninvasive, convenient, and tissue-specific therapeutic strategy for retinal aging.

P040 Night Shift Work and Disease: A Systematic Review of the Role of Oxidative Stress

Abstract Night shift workers make up an essential part of the modern workforce. However, night shift workers have higher incidences of late in life diseases and earlier mortality. Night shift workers are exposed to constant light and experience circadian rhythm disruption. Sleep disruption is thought to increase oxidative stress, defined as an imbalance of excess pro-oxidative factors and reactive oxygen species over anti-oxidative activity. Oxidative stress can damage cells, proteins and DNA and can eventually lead to varied chronic diseases such as cancer, diabetes, cardiovascular disease, Alzheimer’s and dementia. This review aimed to understand whether night shift workers were at greater risk of oxidative stress and to contribute to a consensus on this relationship. Twelve studies published in 2001–2019 examining 2,081 workers were included in the review. Studies compared both the impact of working a single shift and in comparisons between those who regularly work night shifts and only day shifts. All studies had evidence to support this relationship across a range of oxidative stress indicators, including: increased DNA damage, reduced DNA repair capacity, increased lipid peroxidation, higher levels of reactive oxygen species, and to a lesser extent, a reduction in antioxidant defence. This research supports the theory that melatonin and the sleep wake cycle mediate the relationship between shift work and oxidative stress. It is concluded that night shift work increases the risk for oxidative stress and therefore future disease. Recommendations are made to promote the long-term health of shift workers considering these findings.

Oxidative Stress and Localization Status of Hepatocellular Transporters: Impact on Bile Secretion and Role of Signaling Pathways.

Significance: Most hepatopathies are primarily or secondarily cholestatic in nature. Oxidative stress (OS) is a frequent trait among them, and impairs the machinery to generate bile by triggering endocytic internalization of hepatocellular transporters, thus causing cholestasis. This is critical, since it leads to accelerated transporter degradation, which could explain the common post-transcriptional downregulation of transporter expression in human cholestatic diseases. Recent Advances: The mechanisms involved in OS-induced hepatocellular transporter internalization are being revealed. Filamentous actin (F-actin) cytoskeleton disorganization and/or detachment of crosslinking actin proteins that afford transporter stability have been characterized as causal factors. Activation of redox-sensitive signaling pathways leading to changes in phosphorylation status of these structures is involved, including Ca2+-mediated activation of "classical" and "novel" protein kinase C (PKC) isoforms or redox-signaling cascades downstream of NADPH oxidase. Critical Issues: Despite the well-known occurrence of hepatocellular transporter internalization in human hepatopathies, the cholestatic implications of this phenomenon have been overlooked. Accordingly, no specific treatment has been established in the clinical practice for its prevention/reversion. Future Directions: We need to improve our knowledge on the pro-oxidant triggering factors and the multiple signaling pathways that mediate this oxidative injury in each cholestatic hepatopathy, so as to envisage tailor-made therapeutic strategies for each case. Meanwhile, administration of antioxidants or heme oxygenase-1 induction to elevate the hepatocellular levels of the endogenous scavenger bilirubin are promising alternatives that need to be re-evaluated and implemented. They may complement current treatments in cholestasis aimed to enhance transcriptional carrier expression, by providing membrane stability to the newly synthesized carriers. Antioxid. Redox Signal. 35, 808-831.

Oxidative Stress: A Double Edged Sword

Oxidative stress (OS) in simple words is defined as a state of imbalance between antioxidant and pro-oxidants defenses. The purpose of this article is to find out the connection of oxidative stress and free radical species with different aspects of human health. Owing to its harmful effects on proteins and nucleic acids, oxidative stress causes chronic diseases such as cardiovascular and neurodegenerative diseases, diabetes and cancer. It highlights the impacts of antioxidants and pro-oxidants particularly on fertility and infertility. It also focuses on the adverse effects caused by the long-term exposure to pro-oxidant factors leading to structural defects of mitochondrial DNA. As modern life style consists of more reliance on the processed foods and lack of physical activity, a nutrition deficiency, which is common in the present lifestyle, is also one of the reasons for oxidative stress to cause inflammation. However, this review also focuses on how diet affects and triggers inflammation. Redox mechanism with potential threats to health of mankind is discussed, how mere stress can provoke biological stress responses leading to development of disease or metabolic errors. Methods for reduction of oxidative stress are discussed in this review. It also highlights mitochondria as an aging factor as many ROS, particularly mitochondria ROS contribute directly to aging in human body. We will be discussing the recent findings in the oxidative stress field and its negative and positive impacts on human health.

Oxidative stress and peripartum outcomes (Review).

Pregnancy, labor and childbirth are accompanied by excessive oxidative aggression. The excessive formation of free radicals [reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorine reactive species (CRS)] causes cellular oxidative damage, which can be scavenged by enzymatic or non-enzymatic antioxidants in normal healthy pregnancy, physiological labor and delivery without any complications. An imbalance between the pro-oxidant and antioxidant factors may lead to oxidative stress, which contributes to the development of many diseases. This oxidative aggression can be a precursor for pathologies in the pregnant woman including eclampsia, miscarriage, preterm labor, and intrauterine growth retardation; in the offspring it may lead to bronchopulmonary dysplasia/chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity, and periventricular leukomalacia. This review summarizes the studies conducted to identify the mechanisms of oxidative stress and the effect of cell membrane oxidation, the mechanisms that are behind oxidative stress-related diseases, and also those studies which have demonstrated the effect of antioxidants in preventing diseases or diminishing the effects of oxidative stress in the body, in obstetrics and neonatology.

Pathogenic role of the SP/ NK1R system in GBM cells through inhibiting the thioredoxin system.

Objective(s):Glioblastoma multiforme (GBM), a highly aggressive Grade IV brain tumor, is a significant public health issue due to its poor prognosis and incurability. Neuropeptide substance P (SP) plays a critical role in GBM tumor growth and development via activation of neurokinin-1receptor (NK1R). Moreover, SP is a pro-oxidant factor contributing to oxidative stress in various cell types. However, the link between SP and oxidative stress in cancer cells is not fully investigated. Here, we aimed to identify the effects of SP and NK1R antagonist, aprepitant, on the redox status of GBM cells.Materials and Methods:Resazurin assay was employed to determine the effect of aprepitant on viability of U87 glioblastoma cells. 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) assay was employed to measure the levels of intracellular reactive oxygen species (ROS). A quantitative real-time polymerase chain reaction was applied to measure the expression of proteins of the thioredoxin system. Commercial kits (ZellBio GmbH) were also used to measure the enzymatic activity of these proteins.Results:We found that SP increased ROS level in U87 GBM cells, and aprepitant significantly reduced this effect. Furthermore, we found that SP could also affect the thioredoxin system, a central antioxidant enzyme defense system. SP reduced both expression and enzymatic activity of the thioredoxin system’s proteins, Trx and thioredoxin reductase (TrxR) and these effects were significantly reduced by aprepitant. Conclusion:Our results indicated that SP activation of NK1R represented a link between oxidative stress and GBM and highlighted the need for further validations in future studies.