Free Radical Analytical System Research Articles

Comparison of Oxidative Stress Levels in Healthy Children and Children with Allergic Rhinitis.

Background/aim: Allergic rhinitis (AR) is characterized by chronic inflammation of the nasal mucosa. Under the influence of exogenous factors - allergens, reactive oxygen species (ROS) are released during cellular metabolism. They induce a series of pathological changes in the mucosa. Oxidative stress is а result of an imbalance between the production of ROS and the ability to neutralize them. The aim of this study is to compare the levels of oxidative stress between healthy children and children with allergic rhinitis. Material and methods: A total number of 60 children were included (30 healthy children and 30 children with AR). The oxidative stress index was determined by using the FRAS 5 (Free Radical Analytical System) Bravo system. Demographic characteristics, medical history, children's living conditions and eating habits were obtained from the questionnaire. Anthropometric measurements and the absolute number of eosinophils in the peripheral smear were performed on each child. Results: This study showed high oxidative stress index and a significantly higher value of the absolute number of eosinophils in the peripheral smear in children with AR in comparison to healthy children (p<0.05). The group of children with AR had more atopic characteristics and was more exposed to passive smoking than healthy children. Conclusion: Compared to healthy children, children with AR have a high index of oxidative stress, despite of the very high mean value of the concentration of water-soluble antioxidants in serum (PAT test) in the group of children with AR.

Plasma ascorbic acid, antioxidant capacity, and reactive oxygen species in healthy foals.

To describe ascorbic acid (AA) concentrations, plasma antioxidant capacity (PAC) and markers of oxidative stress, as measured by derivatives of reactive oxygen metabolites (dROMs), in healthy foals at birth and during the first month of life. Venous blood samples were collected from healthy Standardbred (n = 13) and Quarter Horse (n = 10) foals. Plasma AA, PAC, and dROMs were assessed at 3 to 12 hours, 3 days, and 1, 2, and 4 weeks of age. AA was measured via high-performance liquid chromatography. PAC and dROMs were measured with a free radical analytical system. Comparisons of AA, PAC, and dROMs at different time points were assessed. Mean ± standard deviation AA concentrations at 3 to 12 hours (44.7 ± 19.6 μmol/L; P ≤ .01), 1 (48.6 ± 22.5 μmol/L; P ≤ .001), and 2 weeks (41.8 ± 15.8 μmol/L; P ≤ .001) were higher than at 4 weeks of age (28.5 ± 12.7 μmol/L). Both PAC and dROMs significantly increased at different time points compared to 3 to 12 hours of age. Healthy foals have higher plasma AA concentrations shortly after birth, which then gradually decrease throughout the first month of life, suggesting that AA may represent a key antioxidant in the postnatal period. The concurrent increase in PAC and dROMs suggests that dynamic development of oxidative balance occurs after birth in foals. Development of AA, PAC, and dROM reference ranges in healthy foals could be used to guide therapeutic interventions and monitor during disease states characterized by increased oxidative stress.

Effects of enzymatically modified isoquercitrin in supplementary protein powder on athlete body composition: a randomized, placebo-controlled, double-blind trial

BackgroundEnzymatically modified isoquercitrin (EMIQ), a water-soluble quercetin, has been shown to intensify muscle hypertrophy in mice. We investigated the effect of EMIQ in supplementary protein powder on athlete body composition.MethodsForty Japanese males who played American football (age: 19.8 ± 1.4 years; body height: 174.1 ± 6.0 cm; body mass: 75.5 ± 10.7 kg) were assigned to a randomized, placebo-controlled, double-blind trial of parallel group. Participants received either EMIQ in whey protein (EW, n = 19) or contrast whey protein (W, n = 20) 6 days per week over 4 months. Body composition was assessed using dual-energy X-ray absorptiometry. Markers of oxidative stress, derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP), were assessed using a free radical analytical system. Data were analyzed using a univariate and repeated measures general model statistics.ResultsAfter 4 months, changes in lower limb fat-free mass and muscle mass were significantly greater in the EW group than in the W group (mean change ±95% CI; W: 324.1 ± 284.3, EW: 950.3 ± 473.2, p = 0.031, W: 255.7 ± 288.6, EW: 930.9 ± 471.5, p = 0.021, respectively). Moreover, the EW group exhibited a significantly higher BAP/d-ROMs ratio, antioxidation index, than the W group after 4 months (mean change ± SD; W: 8.8 ± 1.1, EW: 10.3 ± 2.8; p = 0.028). No significant differences in body mass, lean body mass, fat mass, or lower limb fat mass were observed between the groups.ConclusionIngestion of EMIQ in supplementary protein powder for 4 months exerts antioxidant effects and increases muscle mass among American football players.Trial registrationUniversity Hospital Medical Information Network Clinical Trial Registry, UMIN000036036. Retrospectively registered in 2019.

Serum Reactive Oxygen Metabolite Levels Are Associated with Poor Prognosis in Patients with Diffuse Large B-Cell Lymphoma

[Introduction] Oxidative stress caused by the increased production of reactive oxygen species (ROS) or decreased efficacy of the antioxidant system is implicated in the pathogenesis of various disease entities, such as atherosclerosis, cardiovascular disease, renal failure, malignant tumors, and autoimmune diseases. Recent observations suggested that oxidative stress is closely related to all aspects of cancer. Oxidative stress markers are prognostically important in various cancers including diffuse large B-cell lymphoma (DLBCL). However, the prognostic role of serum reactive oxygen metabolites (ROMs) in DLBCL is still unknown. The objective of this study is to evaluate the role of serum ROMs in patients with DLBCL.[Methods] We enrolled 52 patients with DLBCL who were treated at our institution between 2012 and 2014. To assess oxidative stress, instead of measuring serum ROS directly, we measured serum d-ROMs (the derivatives of Reactive Oxygen Metabolites) levels. In the present study, serum d-ROMs levels were prospectively examined in 52 patients with DLBCL and 12 healthy subjects by using the Free Radical Analytical System 4 (FRAS 4, Wismerll Co. Ltd., Tokyo, Japan). The d-ROMs test has been successfully used to evaluate oxidative stress in a very large number of studies on humans and animals. The d-ROMs test essentially determines the concentration of hydroperoxides in the blood, which are substances that belong to a broad class of reactive oxygen metabolites. The d-ROMs concentration is expressed in Carratelli Units (1 CARR U = 0.08mg hydrogen peroxide/dl). The study protocol and sampling were approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki.[Results] The median follow-up time was 52 months. Median age at diagnosis was 74 years (range, 39-91 years) and 60% were male. 34 patients (65%) were stage 3-4 and 33 patients (63%) were R-IPI poor risk. The serum d-ROMs levels in patients with DLBCL were significantly elevated compared with normal controls (578.9+/-194.3 vs. 286.8+/-24.2 CARR U, P<0.001). In 52 DLBCL patients, patients with high serum d-ROMs levels (≥513 CARR U) had significantly shorter overall survival (OS) than those with low serum d-ROMs levels (<513 CARR U) (5-year OS, 37.9% versus 77.7%, respectively; P<0.001) (Figure. 1). In multivariate analysis, parameters having independent adverse significance for OS were: high serum d-ROMs levels (≥513 CARR U) (p=0.002, HR 5.17), high LDH levels (p=0.008, HR 4.58), and extranodal involvement >1 (p=0.002, HR 4.57).[Conclusion] In the present study we demonstrated that elevated serum d-ROMs levels are associated with poor prognosis in patients with DLBCL. In particular, our data proved that a high serum d-ROMs level is an independent prognostic factor for survival in patients with DLBCL. These results suggest that oxidative stress may have an important role in DLBCL and may be also a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Oxidative Stress Is Associated with Poor Prognosis in Patients with Follicular Lymphoma

[Introduction] Follicular lymphoma (FL) is an indolent non-Hodgkinfs lymphoma (NHL), with a highly variable clinical course that can range from indolent to rapidly progressive disease, including the transformation to aggressive NHL. Oxidative stress caused by the increased production of reactive oxygen species (ROS) or decreased efficacy of the antioxidant system is implicated in the pathogenesis of various disease entities, such as atherosclerosis, cardiovascular disease, renal failure, malignant tumors, and autoimmune diseases. Recent observations suggested that oxidative stress is closely related to all aspects of cancer. Oxidative stress markers are prognostically important in various cancers including diffuse large B-cell lymphoma (DLBCL). However, the prognostic role of oxidative stress in FL is still unknown. The objective of this study is to evaluate the role of oxidative stress in patients with FL.[Methods] 8-hydroxy-2-deoxyguanosine (8-OHdG), which originates from damaged DNA repaired by non-specific endonucleases and specific glycosylates and is eliminated into urine, is widely used as a sensitive biomarker of oxidative stress. Urinary 8-OHdG levels have been reported to be elevated in patients with various malignancies. In the present study, urinary 8-OHdG levels were prospectively examined in 30 patients with FL by using a novel automatic oxidative stress analyzer, ICR-001. We also evaluated serum d-ROMs (the derivatives of Reactive Oxygen Metabolites) levels by using the Free Radical Analytical System 4 (FRAS 4, Wismerll Co. Ltd., Tokyo, Japan). The d-ROMs test has been successfully used to evaluate oxidative stress in a very large number of studies on humans and animals. The d-ROMs test essentially determines the concentration of hydroperoxides in the blood, which are substances that belong to a broad class of reactive oxygen metabolites. The d-ROMs concentration is expressed in Carratelli Units (1 CARR U = 0.08mg hydrogen peroxide/dl). The study protocol and sampling were approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki.[Results] Median age at diagnosis was 70 years (range, 43-84 years) and 53% were male. According to the WHO pathological grading, grade 1 FL was observed in 16 patients (53%), grade 2 FL in 8 patients (27%), and grade 3 FL in 6 patients (20%). FLIPI scores were 0 to 1 in 27%, 2 in 27%, and 3 to 5 in 46%.The urinary 8-OHdG levels in patients with FL (N=30) were elevated compared with normal controls (N=20) (19.7+/-10.3 vs. 13.7+/-3.4 ng/mg/Cr, P=0.01). In 30 FL patients, patients with high urinary 8-OHdG levels (over 23.9 ng/mg/Cr) had significantly shorter overall survival (OS) than those with low urinary 8-OHdG levels (under 23.9 ng/mg/Cr) (3-year OS, 33.3% versus 90.5%, respectively; P<0.001) (Figure. 1). The serum d-ROMs levels in patients with FL were significantly elevated compared with normal controls (543.9+/-199.4 vs. 281.1+/-25.9 CARR U, P<0.001). Patients with high serum d-ROMs levels (over 519 CARR U) had significantly shorter overall survival (OS) than those with low serum d-ROMs levels (under 519 CARR U) (3-year OS, 41.7% versus 94.4%, respectively; P<0.001) (Figure. 2). In univariate analysis, high 8-OHdG levels, high d-ROMs levels, high PS, high LDH levels, high tumor burden (GELF criteria), high beta-2 microglobulin levels, and high FLIPI score were associated with poor OS in patients with FL. In multivariate analysis, parameters having independent adverse significance for OS were: high serum d-ROMs levels (over 519 CARR U) (p=0.01, HR 15.68), high LDH levels (p=0.02, HR 12.25).[Conclusion] In the present study we demonstrated that elevated urinary 8-OHdG levels and serum d-ROMs levels are associated with poor prognosis in patients with FL. In particular, our data proved that a high serum d-ROMs level is an independent prognostic factor for survival in patients with FL. These results suggest that oxidative stress may have an important role in FL and also may be a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. [Display omitted] [Display omitted] DisclosuresNakazato:Mundipharma KK: Research Funding.

Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.

Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

A systematic review of diagnostic clinical prediction rules for low back pain

for eight weeks. Oxidative stress and antioxidant activity were measured by Free Radical Analytical System 4. Statistical analysis was performed by IBM SPSS Statistics 21.0 and Scheffe’s test was used for multiple comparison among the three groups with statistical significance of P< 0.05. Results: When these animals grew to adulthood eight weeks after starting the experiment, oxidative stress at rest was significantly high only in Group J by 28.2% relative to Group C (P< 0.05). Oxidative stress at rest significantly increased in all groups at eight weeks compared to the preexperimental state (all P< 0.001). A comparison of preand post-experimental antioxidant activity in all groups showed a significant decrease in Groups C and T at eight weeks (all P< 0.001). Conclusion(s): An increase in oxidative stress can surpass anti-oxidative stress activity depending on the intensity, duration, and types of exercise. Our study also implied that oxidative stress may increase with musculoskeletal growth in adulthood. Particularly for exercise in the growth stage, it was suggested that active oxygen produced by muscle damage through anaerobic exercise such as jumping had a greater effect on oxidative stress than that by aerobic exercise. It was also indicated that antioxidant activity constantly changes to control oxidative stress within a certain level in response to an increase in oxidative stress. Implications: Our study suggested that anaerobic exercise in the growth stage can help enhance antioxidant activity. However, exercise itself can possibly inflict serious damage on the living body. Therefore, exercise in the growth stage should be demonstrated with good consideration of exercise modality and load. These results are helpful as preclinical data for pediatric physiotherapy.

Identification of clinical parameters associated with serum oxidative stress in patients with rheumatoid arthritis

Objectives. Reactive oxygen species (ROS) are considered to be involved in the pathobiology of rheumatoid arthritis (RA); however, their association with disease activity has not been elucidated. In this study, we measured reactive oxygen metabolites (ROM) in patients with RA using a new Free Radical Analytical System and determined clinical parameters associated with ROM.Methods. One hundred and fifty-two patients with RA and 80 patients with diabetes mellitus (DM) were included in this observational study. To measure ROM, the d-ROM test was performed on blood samples drawn from all subjects. The correlation between ROM and biomarkers, disease activity, doses of methotrexate (MTX), and prednisolone (PSL) were investigated.Results. There were significant, positive correlations between ROM and CRP, matrix metalloproteinase 3 (MMP3), Disease Activity Score 28–erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). Multiple regression analysis revealed that CRP and DAS28-ESR were correlated with ROM.Conclusions. The serum level of ROM was associated with CRP and DAS28-ESR, suggesting that ROM, in conjunction with CRP and MMP3, may be able to be used as a new biological disease marker to evaluate the disease activity of RA.

Pilot study of preoperative immunonutrition with antioxidants in living donor liver transplantation donors.

Previous studies have demonstrated that oxidative stress by mediating the excessive production of reactive oxygen species is involved in tissue damage and organ failure during and after surgery. The impact of the preoperative immunonutrition including antioxidants on the postoperative course of patients undergoing hepatic surgery was investigated in this pilot study. Twenty-three living donor liver transplantation (LDLT) donors were randomly assigned to either an experimental (AO) group, received a commercial supplement enriched with antioxidant nutrients for each of the 5 days immediately prior to surgery while maintaining normal food intake, or a control (CT) group, administered no supplement. Antioxidative capacity was measured by spectrophotometry of patient serum using a free-radical analytical system. The antioxidative capacity of 90.9% patients in the AO group increased after immunonutrition. Compared to the CT group, the AO group was found to have higher antioxidant capacity and transferrin levels; lower WBC, lymphocyte, and neutrophil counts; and briefer duration of postoperative fever during the postsurgical period. No significant differences were found between the 2 groups regarding the nutritional parameters; liver functioning parameters; immunological parameters; intraoperative factors; postoperative outcomes. Preoperative immunonutrition including antioxidants might play a beneficial role in improving postsurgical immunological response but the modest biological advantage was not associated with any significant clinical outcome.

SAT0113 Intense Repression of Serum Oxidative Stress Marker in Rheumatoid Arthritis Cases Treated with Tocilizumab: Cross Sectional and Longitudinal Evaluation

BackgroundOxidative stress induced by reactive oxygen species (ROS) is also an important mechanism that underlies destructive and proliferative synovitis in rheumatoid arthritis (RA). Abundant amounts of reactive oxygen species have...

Reduction of oxidative stress in liver cancer patients by oral green tea polyphenol tablets during hepatic arterial infusion chemotherapy

Hepatic arterial infusion chemotherapy (HAI) using an implanted port system is the standard regimen for primary and metastatic liver cancers (MLCs). However, there have been few studies concerning HAI-induced oxidative stress and damage to the liver or other organs. The aim of the present study was to investigate the ability of green tea polyphenols (GTPs) to reduce the oxidative stress or increase the biological antioxidative potential in HAI-treated patients. A total of 19 patients with inoperable hepatocellular carcinoma (HCC) or MLC from colorectal malignancy were eligible for HAI with cisplatin (CDDP) and 5-fluorouracil (5FU). The study subjects were randomly assigned to either a 3 or a 6 oral GTP tablets per day group. Each tablet had a GTP content equivalent to 79 mg of epigallocatechin-3-gallate. The oxidative stress was assessed by measuring the levels of derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidative potential (BAP) values in patient plasma using the Free Radical Analytical System 4 (FRAS4), and correlating the results with clinical laboratory data for the patients. The levels of d-ROMs were significantly reduced by the oral intake of 6 GTP tablets for 6–9 months (P=0.0463) but were not significantly reduced by the oral intake of 3 GTP tablets daily. BAP values remained constant in the 3 and 6 tablet groups for 6–9 months during the follow-up study. The total serum bilirubin (T-bil) levels increased significantly at 3 (P=0.028) and 9 (P=0.0151) months and the red blood cell (RBC) count decreased at 6 months (P=0.0458) after intake for the 6 GTP tablet group. Alkaline phosphatase (ALP) levels increased significantly at 9 months (P=0.0298). Cholinesterase (ChE) decreased significantly at 9 (P= 0.0127) and 12 (P= 0.0207) months after intake for the 3 GTP tablet group. The results indicate that the daily intake of 6 GTP tablets containing 474 mg polyphenols significantly reduces HAI-induced oxidative stress in HCC or MLC patients while the antioxidative potentials of the patients remain constant.

Effects of Cyclosporine on Oxidative Stress in Human Bronchial Epithelial Cells

ObjectivesSome of the airway complications relate to the use of cyclosporine (CsA), a potent agent widely used after organ transplantations. Several recent studies have demonstrated CsA treatment to induce reactive oxygen species (ROS). The present study was undertaken to investigate effects of CsA on production of ROS and antoxidant defense of airway cells using the human bronchial epithelial cell line BEAS-2B. MethodsWe measured biological antioxidant potential (BAP), as well as ROS and malondialdehyde levels in BEAS-2B cells after CsA treatment, using Free Radical Analytical System 4 kits (Diacron, Grosseto, Italy). ROS production was expressed as Carr Units as established by the manufacturer and BAP as μmol/2 × 105 cells; malondialdehyde, by the thiobarbituric acid assay. ResultsROS production was increased in the BEAS-2B cells after CsA treatment: 73.5 at 0 (controls); 82.5 at 10; 84.0 at 30; 86.0 at 50; and 93.0 Carr Unit/2 × 105 cells at 100 μg/mL of CsA. The levels of BAP were 1821 at 0 (controls), 1698 at 10; 1653 at 30; 1366 at 50 μg/mL; and 1391 at 100 μg/mL. The levels of malondialdehyde were increased: 3.8 at 0 (controls); 3.4 at 10; 4.4 at 30; 4.2 at 50: and 5.0 nmol/106 cells at 100 μg/mL. ConclusionsIncreased production of ROS and decreased BAP by CsA in BEAS-2B cells may increase malondialdehyde levels by radical-induced damage.

Evaluation of the Time Course of Oxidative Stress in Patients with Sudden Sensorineural Hearing Loss

In recent years, several studies have been reported on the relationship between oxidative stress and various disorders including some inner ear disorders such as noise-induced hearing loss, drug-induced ototoxicity and age-related hearing loss. In this study, we investigated oxidative stress in 39 patients with sudden sensorineural hearing loss (SSNHL) using Free Radical Analytical System 4 (FRAS4). We compared the oxidative stress levels at before treatment to the levels at one and four weeks after treatment. The oxidative stress level with SSNHL exhibited higher values than the upper limit of the normal value. Furthermore after treatment, oxidative stress levels decreased in most of the patients. Next, we evaluated the relationship between oxidative stress levels and hearing recovery grades. In the patient group with complete and marked recovery, the oxidative stress levels before treatment were higher than the levels in the patients group with slight recovery and no recovery. No statistical significance was observed in the oxidative stress levels evaluated at after treatment between those two groups. Our findings suggest that SSHNL is related to oxidative stress at the onset period, and the oxidative stress levels before treatment can predict the hearing prognosis in the SSHNL patients.

Oxidative Stress in Preretinopathic Diabetes Subjects and Antioxidants

This study assessed the effect of a systemic oral treatment with antioxidants (AOs) in preretinopathic diabetes (PRD) patients, through the evaluation of oxidative stress in plasma and changes in the full-field electroretinogram (ERG). Thirty-two PRD subjects with good metabolic control were recruited. Patients were randomized in two groups, one of which received oral AO treatment with α-lipoic acid at 400 mg/day in association with genistein and vitamins, whereas the other group received a placebo. Free radicals and the AO barrier were evaluated in plasma with the Free Radical Analytical System 4 instrument (H&D srl, Parma, Italy), and the same day the electrophysiological response was measured by ERG. These analyses were performed at enrollment and after 30 days of treatment. Statistically significant increases of plasma AO levels and ERG oscillatory potential values were observed in the group treated with AO, but not in the control group. Results of this preliminary study suggest that an oral treatment with AOs in PRD subjects may have a protective effect on retinal cells, as detected by ERG analysis, through the strengthening of the plasma AO barrier.

Oxidative Stress Levels in Myelodysplastic Syndrome Patients: Their Relationship to Serum Ferritin and Haemoglobin Values

Reactive oxygen species (ROS) and serum ferritin levels are both considered to be important biological factors in the pathogenesis of myelodysplastic syndrome (MDS). This study evaluated the levels of ROS in 40 patients with MDS (19 males and 21 females) using the Free Radical Analytical System, FRAS4, and derivatives of reactive oxygen metabolite kits. The patients' mean age was 67.3 years (range 58 - 86 years). The sera of 34 (85%) patients exhibited higher levels of oxidative stress than the reference range. There was a positive correlation between ROS levels and serum ferritin levels, and a negative correlation between ROS levels and haemoglobin levels. There was a negative relationship between serum haemoglobin and ferritin levels. The results indicated that iron accumulation or severe anaemia could contribute to oxidative stress in MDS patients. Iron chelation and antioxidant therapy may be suitable for the management of MDS.

Serum level of oxidative stress marker is dramatically low in patients with rheumatoid arthritis treated with tocilizumab

Regarding the pathobiology of rheumatoid arthritis, oxidative stress induced by reactive oxygen species is an important mechanism that underlies destructive and proliferative synovitis. Abundant amounts of reactive oxygen species have been detected in the synovial fluid of inflamed rheumatoid joints. It is reported that drugs that block tumor necrosis factor-α reduce the oxidative stress marker levels in patients with rheumatoid arthritis. In this study, we measured reactive oxygen species using a free radical analytical system in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, tumor necrosis factor-α-blocking drugs (infliximab, etanercept), and an interleukin-6-blocking drug (tocilizumab). The serum level of oxidative stress was drastically low in patients with rheumatoid arthritis treated with tocilizumab, suggesting that interleukin-6 blocking therapy reduces not only joint damage, but also vascular degeneration in patients with rheumatoid arthritis. We believe that such a drastic effect would reduce the incidence of cardiovascular events and mortality in patients with rheumatoid arthritis.

Analysis of reactive oxygen metabolites (ROMs) after cardiovascular surgery as a marker of oxidative stress.

The transient systemic low perfusion that occurs during cardiovascular surgery leads to oxidative stress and the production of free radicals. A systemic increase of various markers of oxidative stress has been shown to occur during cardiopulmonary bypass (CPB). However, these markers have not been adequately evaluated because they seem to be reactive and short-lived. Here, oxidative stress was measured using the free radical analytical system (FRAS 4) assessing the derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Blood samples were taken from 21 patients undergoing elective cardiovascular surgery. CPB was used in 15 patients, and abdominal aortic aneurysm (AAA) surgery without CPB was performed in 6. Measurements of d-ROMs and BAP were taken before surgery, 1 day, 1 week, and 2 weeks after surgery, and oxidative stress was evaluated. The d-ROM level increased gradually after cardiovascular surgery up to 2 weeks. Over time, the d-ROM level after surgery involving CPB became higher than that after AAA surgery. This difference reached statistical significance at 1 week and lasted to 2 weeks. The prolongation of CPB was prone to elevate the d-ROM level whereas the duration of the aortic clamp in AAA surgery had no relation to the d-ROM level. The BAP was also elevated after surgery, and was positively correlated with the level of d-ROMs. In this study, patients who underwent cardiovascular surgery involving CPB had significant oxidative damage. The production of ROMs was shown to depend on the duration of CPB. Damage can be reduced if CPB is avoided. When CPB must be used, shortening the CPB time may be effective in reducing oxidative stress.

Effects of Cyclosporine on the Antioxidant Status and Oxidative Stress in the Glioma Cells

ObjectivesAfter organ transplantation, some patients suffer neurological complications. Among the immunosuppressants, cyclosporine can cause neurological side effects. However, the mechanisms of encephalopathy by cyclosporine are not fully understood. We measured the antioxidant status, the hydrogen peroxide level, and the malondialdehyde level in glioma cells after cyclosporine treatment. MethodsThe production of hydrogen peroxide was determined using a modified xylenol orange method. The amount of malondialdehyde was measured using the thiobarbituric acid assay. Total antioxidant status was measured using Free Radical Analytical System 4 with kits. ResultsCyclosporine resulted in the production of hydrogen peroxide by the glioma cells. The increased production of hydrogen peroxide depended on the drug concentration. The antioxidant status was decreased in the glioma cells after cyclosporine treatment. The malondialdehyde level was not changed in glioma cells after cyclosporine treatment. ConclusionsIncreased production of reactive oxygen species and decreased antioxdant status by cyclosporine in glioma cells may contribute to neurological side effects in transplantation patients.

Serum derivative of reactive oxygen metabolites (d‐ROMs) in pediatric hemato‐oncological patients with neutropenic fever

Early markers for predicting the severity of neutropenic fever (NF) in patients with hemato-oncological patients have not yet been established. Reactive oxygen species are known to play an important role in the antimicrobial function of neutrophils. The aim of this study was to determine the serum levels of derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) levels in these patients, and to investigate the associations between these levels and the severity of NF. Twenty-seven pediatric hemato-oncological patients were enroled in this prospective study. Their median age was 10 years (range 1-19). Laboratory samples for C-reactive protein (CRP), d-ROMs, and BAP were collected at the onset of NF. The Free Radical Analytical System 4(R) was used to measure levels of d-ROMs and BAP. A total 36 NF episodes were evaluated. Levels of d-ROMs in NF patients with systemic inflammatory response syndrome (SIRS, n = 7) were significantly lower than those in subjects without SIRS (n = 29; 197.6 vs. 314.1 U.CARR, P = 0.017). There were no statistically significant differences in CRP, BAP, WBC count, or neutrophil count at the onset. The peak levels of CRP were significantly higher in patients with SIRS than in those without SIRS (23.9 vs. 6.1 mg/dl, P = 0.0003). Patients with low level of d-ROMs at the onset of NF should be observed stringently since they possibly have severe NF.

010 Détermination du cycle des radicaux libres et effets cliniques chez les patients soumis à un régime alimentaire déterminé et rôle des anti-oxydants

The study was conducted to assess the role of antioxidants in the treatment of DMS, assessing their performance in relation to therapy. Have been highlighted some data that suggest the importance of food in the prevention of DMS and progression of the initial or intermediate stage of the disease. The hypothesis of oxidative stress in DMS is based on the deterioration of antioxidants systems in the retina. In our study, we evaluated for 12 consecutive months, 40 patients with AMD and we divided them into two groups. The first group (study group) was treated with antioxidants associated with a specific diet. The second group followed the recommended diet. Patients were regularly subjected to tests that included a careful control of the investigation fundus with a slit lamp associated with retinografia. Moreover, both before and during treatment was performed an assessment of oxidative stress of each patient, using a new technique that uses an innovative tool for the study of free radicals, the FRAS-4 (Free Radical Analytical System). With the FRAS-4, we run the d-ROMs test for determination of hydroperoxide in blood, on the assumption that there is a strong correlation between the amount of free radicals in blood and the development of DMS. A distance of 12 months, all patients treated with antioxidants associated with the special diet recommended by us were stable. In the control group, the deterioration was seen in both morphological and from the functional, with a further reduction in visual acuity. The most important on which to focus was the reduction in the levels of free radicals produced in the study group undergoing therapy with antioxidants, highlighted with the d-ROMs test at the end of treatment. Quantitative Analysis of data collected shows that the administration of antioxidants (and the consequent reduction in the circulation of ROM, assessed with the d-ROMs test), reduces the risk of progression of DMS.