Biomarkers Of Oxidative Stress Status Research Articles

Oxidative Stress Status in Post Stroke Patients: Sex Differences.

After a cerebral stroke insult, there is an overproduction of Reactive Oxygen Species (ROS), which overcome the antioxidant defenses, causing further tissues damage. The status of oxidative stress in stroke patients over time, particularly in those undergoing rehabilitation treatments, has been poorly investigated. We analyzed the oxidative stress status in 61 subacute stroke patients (33 females and 28 males) admitted to our rehabilitation center by measuring, in serum: hydroperoxides levels (d-ROMs), antioxidant activity (BAP test), and the relative antioxidant capacity (OSI index). We also analyzed patients for glucose levels and lipid profile. In addition, we analyzed the correlation between oxidative stress status biomarkers and motor deficits, disability, and pain. Almost all patients showed high or very high levels of d-ROMs, while BAP levels were apparently in the reference range of normality. Females had lower BAP values (females: 2478 ± 379; males: 2765 ± 590; p = 0.034) and lower OSI index (females: 5.7 ± 1.9; males: 6.8 ± 1.9; p = 0.043). Moreover, in the male group, the correlation with motor impairment and disability showed a worsened motor performance when oxidative stress is higher. Female group, on the other hand, had an unexpected different trend of correlation, probably due to an unbalanced systemic oxidative stress. Further research is needed to see if sex differences in oxidative stress status in subacute stroke patients persist after rehabilitation.

Effect of Vitamin D on Paraxonase-1, Total Antioxidant Capacity, and 8-Isoprostan in Children with Attention Deficit Hyperactivity Disorder.

Method In this double-blind, randomized, placebo-controlled trial, 75 children (aged 6–12) diagnosed with ADHD were randomly assigned into two groups. The supplementation group received vitamin D3 (2000 IU), and the control group received a placebo for 3 months. Blood samples were collected at baseline and after intervention to analyze the 25(OH)D, paraxonase-1 activity (PON-1), Total Antioxidant Capacity (TAC), and 8-isoprostan levels. Results A significant rise in circulating 25(OH)D was observed in the vitamin D group versus the placebo group at the end of the study. There was no reduction in 8-isoprostan levels in the vitamin D group compared to the placebo group. Serum paraxonase-1 and TAC concentration decreased in both groups, but these alterations were not statistically significant in the treatment group versus the placebo group at the end of the intervention. Conclusion Vitamin D supplementation for 3 months did not have beneficial effects on biomarkers of oxidative stress status. To confirm these findings, further studies on children are suggested.

Dietary vitamin D ameliorates hepatic oxidative stress and inflammatory effects of diethylnitrosamine in rats

The generation of reactive oxygen species (ROS) plays an essential role in the pathogenesis of several diseases. Its implication in inflammation has suggested a possible link between oxidative stress and activation/release of cytokines in precancerous states. Recent observational studies have suggested an association between inflammation and vitamin D deficiency; hence, suggesting that vitamin D could play a role in the pathogenesis of diseases. This study examined the antioxidant and anti-inflammatory potentials of vitamin D in diethylnitrosamine (DEN)-induced oxidative stress and inflammation in rats. Rats were divided into four experimental groups. While groups one and two were administered twice weekly with 30 mg/kg body weight DEN for six weeks, groups three and four were given normal saline. Groups one and three were fed with vitamin D deficient diet, while groups two and four were fed vitamin D diet during the experiment. After that, biomarkers of oxidative stress status were assayed spectrophotometrically. The concentration of inflammatory cytokines was determined using enzyme-linked immunosorbent assay (ELISA). DEN-induced vitamin D deficient diet group had increased antioxidant enzymes’ activities. Also, there were elevated concentrations of thiobarbituric acid reactive substances (TBARS) and inflammatory cytokines in the same group. Vitamin D diet, however, reduced oxidative stress effects through the reduction in the activities of TBARS and caused a significant (p < 0.05) increase in nitric oxide concentration. Vitamin D diet significantly (p < 0.05) reduced the level of interleukin 1β and TNF-α produced in the deficiency state. These findings show that vitamin D may play an essential role in the regulation of hepatic oxidative stress and inflammatory responses.

Lipid peroxidation products and their role in neurodegenerative diseases

The central nervous system (CNS) is one of the most metabolically active organs and is characterized by elevated oxygen requirements, while it possesses a diminished anti-oxidative action. This can result in impairment in susceptible glia and neurons, due to the production of reactive oxygen species (ROS), and ultimately neurodegeneration. Indeed, oxidative stress is a key component of the pathophysiological mechanisms in a plethora of diseases, including neurodegenerative disorders. Iron, is additionally involved in oxygen transportation and misregulation of iron can cause neurotoxicity through different mechanisms leading to oxidative damage and cell death. Recent discoveries showing that ROS are capable of commencing lipid peroxidation (LPO), a process in which oxidants assault lipids that contain C-C double bonds and particularly polyunsaturated fatty acids (PUFAs). LPO results in the generation of toxic lipid aldehyde species, including 4-hydroxy-2-nonenal (HNE), malondialdehyde, and acrolein. These reactive aldehyde species are generated within enzymatic pathways that lead to post-transcriptional alterations of DNA and proteins, eventually resulting in genotoxicity, inhibition of gene expression, cytotoxicity and cellular death. Among those various molecules, isoprostanes and neuroprostanes are potential key biomarkers for oxidative stress status in neurological disorders. The aim of this review was to describe LPO process and its products, and to characterize their role as potential biomarkers in neurodegenerative diseases (NDs).

The Mediterranean Lifestyle as a Non-Pharmacological and Natural Antioxidant for Healthy Aging.

Oxidative stress has been suggested to affect age-associated physiological dysfunction. Therefore, it is speculated that antioxidant supplements could have a potential role in preventing age-related diseases and death. Among different dietary habits, the highly antioxidant Mediterranean dietary pattern, which includes high vegetable and fruit intake, consumption of legumes, cereals, and fish, low intake of meat and dairy derivatives, moderate red wine consumption, and use of extra-virgin olive oil, is characterized by other aspects than food, such as conviviality, sensory stimulation, socialization, biodiversity, and seasonality that can reinforce the Mediterranean diet’s (MeD) beneficial effects on wellbeing, quality of life, and healthy aging. The present review aims to discuss available data on the relationship between oxidative stress and aging, biomarkers of oxidative stress status, protective effects of the MeD, and the adoption of the Mediterranean lifestyle as a non-pharmacological and natural tool to cope with oxidative stress damage for a longer life span, and—even more important—healthy aging beyond the biological, psychological, and social challenges that old age entails.

Oxidative stress markers are increased since early stages of infection in syphilitic patients

Clinical symptoms of syphilis are the consequence of the spirochete propensity to induce persistent chronic inflammation, which could participate to oxidative stress increase. The present study was designed to evaluate the level of oxidative stress biomarkers and antioxidant defences in a cohort of syphilitic patients. Serum oxidative status was explored in 63 patients diagnosed with early syphilis, 34 consulting patients negative for syphilis and 19 healthy controls. Total plasma thioredoxin (Trx) and thiols were determined as antioxidant capacity markers, °NO, advanced oxidation protein products (AOPP) and protein carbonyl levels as oxidative stress status biomarkers, and CRP as marker of inflammation. Mean serum levels of Trx, AOPP, carbonyls, and nitrates/nitrites were significantly higher, whereas thiols level was lower in syphilitic patients compared to non-syphilitic patients and healthy controls (respectively, p<0.05/p<0.01 for Trx, p<0.005/p<0.0001 for AOPP, p<0.05/p<0.005 for carbonyls, p<0.005/p<0.05 for nitrates/nitrites and p<0.01/p<0.0001 for thiols). According to the stage of the disease, results highlighted a marked and sustained oxidative stress imbalance from the first stage to the latent period of the disease. Moreover, syphilitic patients presented a low inflammation status reflected by median of CRP level (1.7mg/L, range 5th-95th percentile from <0.1 to 33.7mg/L), correlated with antioxidant capacity decrease (thiols) at stage 1 (r=-0.725; p<0.0001) and nitrosative stress increase (nitrates/nitrites) at stage 2 and latent (respectively, r=0.285, p<0.05 and r=0.650, p<0.05). These findings indicate that at all stages of the disease, despite a low-grade inflammatory state, syphilis infection generates a major oxidative and nitrosative stress which may be involved in the pathophysiology of the disease.

Lipid peroxidation products as oxidative stress biomarkers

Oxidative stress induced by reactive oxygen and nitrogen species has been implicated in the pathogenesis of various disorders and diseases. Biomarkers are needed for assessment of oxidative stress status in vivo and also for health examination, diagnosis at early stage, prognosis, safe and efficient drug development, and evaluation of efficacy of drugs, foods, beverages, and supplements. Lipids are susceptible to oxidation and lipid peroxidation products are potential biomarkers for oxidative stress status in vivo and its related diseases. Recently, isoprostane, isoprostaglandin homologues from arachidonic acid, neuroprostanes from docosahexaenoic acid, hydroxyoctadecadienoic acid from linoleic acid, and oxysterols from cholesterol have received much attention as potential biomarkers for oxidative stress status in vivo. The physiological levels of these lipid peroxidation products and potential application as biomarkers will be reviewed.

RETRACTED: Biomarkers for oxidative stress status of DNA, lipids, and proteins in vitro and in vivo cancer research

Oxidation and the production of free radicals are an integral part of human metabolism, and oxidative stress is related to many diseases, including cancer and heart disease. The use of biomarkers for oxidative stress may provide further evidence of a causal relationship between oxidative damage to macromolecules (DNA, lipids, and proteins) and cancer. A wide variety of functional assays, both in vivo and ex vivo, include various measures of DNA oxidation (oxidized DNA bases such as 8-OHdG, autoantibodies to oxidized DNA, modified comet assay), lipid oxidation (thiobarbituric acid-reactive substances, exhaled pentane/ethane, low-density lipoprotein resistance to oxidation, isoprostanes), and protein oxidation (protein carbonyls). The objective of this review is to discuss characteristics and methodologic issues for studies involving biomarkers of exposure to antioxidant nutrients and of oxidative stress status. This paper provides an overview on the current knowledge of oxidative DNA, lipid, and protein damage and cancer incidence.

Oxidized Forms of Glutathione in Peripheral Blood as Biomarkers of Oxidative Stress

Reduced glutathione (GSH) and its redox forms, glutathione disulfide (GSSG) and glutathionylated proteins (PSSG), are biomarkers of oxidative stress, but methodologic artifacts can interfere with their measurement. We evaluated the importance of correct sample handling during the preanalytical phase for GSH, GSSG, and PSSG measurement. We used human blood for in vitro experiments with oxidants [tert-butylhydroperoxide (t-BOOH), diamide, and menadione]. For in vivo experiments, we used rats in which we cannulated the jugular and femoral veins for both oxidant administration and blood collection. We measured GSH, GSSG, and PSSG with HPLC with or without sample pretreatment with N-ethylmaleimide (NEM) to prevent artifacts. We also measured malondialdehyde (MDA) with HPLC, and protein carbonyls (PCO) with spectrophotometric procedures. When methodologic artifacts were prevented by pretreatment with NEM, GSSG results increased up to 3-fold over the basal concentrations, even in the presence of 5 micromol/L t-BOOH or diamide and 20 micromol/L menadione. PSSG increased by approximately 50% at 20 micromol/L t-BOOH or diamide and at 50 micromol/L menadione. PCO and MDA remained unchanged. In vivo oxidation treatments elicited immediate and significant increases in GSSG and PSSG over basal values (up to 200-fold), whereas PCO and MDA showed only slight variation 120 or 180 min after treatment. With the use of artifact-free measurement methods, GSH, GSSG, and PSSG are potentially powerful and reliable biomarkers of oxidative stress status and can be used to evaluate whether, and to what extent, oxidative stress may be involved in various diseases.

Les isoprostanes, biomarqueurs de peroxydation lipidique chez l'homme. Partie 1. Nomenclature et synthèse

The synthesis of prostaglandins has been a subject of chemical attractiveness for the last 40 years with the successful strategy developed by Corey et al. via a formyl-lactone in the trans-PG series, derived from the action of cyclooxygenases (COXs). The non-enzymatic metabolic scheme of arachidonic acid, as a free radical catalyzed mechanism, has introduced new data concerning the reactivity of the arachidonyl radical in the absence of COXs and also a growing interest in the total synthesis of isoprostanes and analogues. The potent biological activity of these compounds has been attracting intense research interest since they were detected in humans as well as animal models in the early 1990s. The measurement of these isoprostanes has been regarded as one of the most useful non-invasive biomarkers for oxidative stress status. Two mechanisms for their biosynthesis have been proposed. In the first mechanism, a peroxyl radical undergoes successive 5-exo cyclizations analogous to the enzymatic mechanism proposed for prostaglandin biosynthesis. The second mechanism starts with a 4-exo cyclization of a peroxyl radical leading to an intermediate dioxetane. During the last two decades, several approaches towards the synthesis of isoprostanes and analogues have been reported in the literature by several groups of chemists. Finally, to date, two nomenclatures have been proposed by Taber et al. and Rokach et al., but only Taber’s nomenclature have been approved by IUPAC.

Mechanisms for the Formation of Isoprostane Endoperoxides from Arachidonic Acid: “DIOXETANE” INTERMEDIATE VERSUSऔ-FRAGMENTATION OF PEROXYL RADICALS

The isoprostanes are a class of autoxidation products generated from arachidonic acid (or its esters) by a free radical initiated process. The potent biological activity of these compounds has been attracting intense research interest since they were detected in humans as well as animal models in the early 1990s. The measurement of these compounds has been regarded as one of the most useful non-invasive biomarkers for oxidative stress status. Two mechanisms for the formation of these compounds have been proposed. In the first mechanism, a peroxyl radical undergoes successive 5-exo cyclizations analogous to the enzymatic mechanism proposed for prostaglandin biosynthesis. The second mechanism starts with a 4-exo cyclization of a peroxyl radical leading to an intermediate dioxetane, a mechanism that has also been proposed for prostaglandin biosynthesis as well as for the formation of 4-hydroxy nonenal (HNE). Autoxidation of cholesteryl-15-HpETE under free radical conditions provides Type IV isoprostanes. The "dioxetane" mechanism for isoprostane generation from 15-HpETE requires that optically pure products are formed from an optically pure reactant, whereas an alternate mechanism for the process involving beta-fragmentation of the 15-peroxyl would give racemic isoprostane products. We have carried out a test of the mechanism based upon these stereochemical requirements. The results of analysis of the product mixture derived from autoxidation of optically pure Ch-15-HpETE by atmospheric pressure chemical ionization-mass spectrometry coupled with chiral high performance liquid chromatography indicate that the major isoprostane diastereomers are formed as a racemic mixture. These experimental results are consistent with a mechanism for isoprostane formation involving beta-fragmentation of the 15-peroxyl radical followed by re-addition of oxygen to form the 11-HPETE peroxyl, and they exclude a mechanism proceeding through the formation of a dioxetane intermediate.

Clinical application of breath biomarkers of oxidative stress status

Isolation and quantification of volatile breath biomarkers indicative of relevant alterations in clinical status has required development of new techniques and applications of existing analytical chemical methods. The most significant obstacles to successful application of this type of sample have been reduction in required sample volume permitting replicate analysis (an absolute requirement for all clinical studies), separation of the analyte(s) of interest from background molecules, water vapor and other molecules with similar physical properties, introduction of automation in analysis and the use of selective detection systems (electron impact mass spectrometry, flame photometric, thermionic detectors), and automated sample collection from the human subject. Advances in adsorption technology and trace gas analysis have permitted rapid progress in this area of clinical chemistry.