Biological Antioxidant Potential Levels Research Articles

CSF biological antioxidant potentials may differentiate neurodegenerative diseases—A preliminary report

AbstractOxidative stress has a significant impact on neurodegenerative diseases. Biological antioxidant potential (BAP) is a rapid measure of total antioxidant properties in the serum. However, few studies measured BAP in cerebrospinal fluid (CSF). We measured CSF BAP in patients with neurodegenerative disease. We had 17 patients with Alzheimer's disease (AD), nine with dementia with Lewy bodies (DLB), 10 with Parkinson's disease (PD), 11 with multiple system atrophy (MSA) patients, with the same background, and 19 healthy subjects as normal controls. We measured CSF BAP using a Free Radical Elective Evaluator. As a result, CSF BAP level in patients with neurodegenerative disease was higher than that in controls. In particular, CSF BAP level in patients with AD was higher than that in patients with DLB (P < 0.05). We also found a close relationship between CSF Tau pT181/beta‐amyloid ratio and BAP in patients with AD (P < 0.01), although this relationship was not found in patients with DLB. In conclusion, CSF BAP may help differentiating AD and DLB.

Aging-Related Oxidative Stress: Positive Effect of Memory Training

The cognitive impairment characterizing the phenotype of older adults has been related to the efficiency of the antioxidant system. This study aimed at investigating the effect of memory training (MT) on memory, global cognitive functioning, and the oxidant and antioxidant capacity of plasma. We recruited 52 healthy subjects aged over 60. Twenty-nine subjects were submitted to 6-months of MT (Experimental Group, EG), and 23 were used as a Control Group (CG). Global cognitive functioning was assessed by the Mini-Mental State Examination (MMSE) and Short- and Long-Term Memory (STM and LTM, respectively) by the Rey Auditory Verbal Learning Test (RAVLT) at baseline (T0) and after 6-months (T1). Meanwhile, Reactive Oxygen Metabolites derivative compounds (d-ROMs), Biological Antioxidant Potential (BAP), and their ratio were evaluated on plasma. Results showed that the MMSE and RAVLT scores improved in EG at T1. At the same time, the d-ROMs levels significantly decreased, while the BAP and BAP/d-ROMs ratio showed an opposite trend. In both groups, the MMSE and LTM scores were negatively associated with d-ROMs levels, and positively correlated with BAP levels and the BAP/d-ROMs ratio. When we considered the Δvalue (Δvariable = variable post-MT minus variable pre-MT) in EG, the ΔMMSE and ΔLTM scores were negatively associated to Δd-ROMs, and positively to ΔBAP and ΔBAP/dROM. In conclusion, our results suggest that MT improves memory and global cognitive functioning. These processes were significantly associated to increase in resistance against oxidative stress at the plasma level in healthy older adults.

Effect of oral carbohydrate with amino acid solution on serum oxidative/anti-oxidative status in healthy volunteers.

The aim of this work was to investigate the effect of oral carbohydrate with amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in healthy persons. Fourteen healthy volunteers were segregated into control and ONS groups. Volunteers in the ONS group ingested 250ml of Arginaid Water (Nestle Japan, Tokyo, Japan) in the evening before the experiment and at 7:00am on the day of the experiment. Volunteers in the control group fasted after dinner and drank only water until 7:00am on the day of the experiment. In both groups, blood was collected at 9:00am. The serum total oxidant levels and antioxidant capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites) test and BAP (biological antioxidant potential) test, respectively. In the ONS group, the serum d-ROMs level was significantly lower than in the control group (297±43 and 327±41 U.CARR, respectively, p=0.018), while the serum BAP level was significantly higher than the control group (2410±432 and 1979±397µmol/l, respectively, p=0.005). The OXY level of Arginaid Water was much higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that an ONS with arginine loading could decrease oxidative stress and increase antioxidant capacity in healthy volunteers.

The effects of exercise load during development on oxidative stress levels and antioxidant potential in adulthood

The objective of this study was to elucidate the impact of physical activity during the growth period as well as on oxidative stress and antioxidative potential in adulthood. The experimental animals used were four-week old male Wistar rats, which were randomly divided into three groups. The exercise loads were as follows: control (CON), treadmill exercise (TE), and jumping exercise (JE). The exercise was performed at the same time of day, at a frequency of five days per week, for eight weeks. Derivatives of reactive oxygen metabolites (d-ROSs) and biological antioxidant potential (BAP) were measured during periods of rest prior to commencement of the experiment and after the experiment. Analysis was conducted using a Wilcoxon signed-rank test and Schaffer’s multiple comparison procedure and the significance level was set at p < 0.05. The percent increase in d-ROM levels in the JE group, which experienced short-duration intense exercise loads, was higher than that in the TE group, which experienced moderately intense exercise loads. However, BAP, which is an index of antioxidant potential, markedly decreased in adulthood in the CON group, as compared to that in the developmental period, whereas the exercise groups showed no notable changes in BAP levels. Oxidative stress levels and antioxidant potential are affected differently in adulthood, depending on the intensity of sustained exercise loads experienced during development. Results suggested that in order to increase antioxidant potential, while taking oxidative stress production into account, moderately intense exercise loads are more desirable than highly intense exercise loads.

Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice.

Whole-wheat intake is known to reduce the risk of metabolic syndrome. However, the active component remains unclear. Recently, we identified bioactive peptides [leucine-arginine-proline (LRP) and leucine-glutamine‑proline(LQP)] from wheat bran autolytic hydrolysate. The present study aimed to investigate the effects of LRP and LQP on non-alcoholic steatohepatitis (NASH) in a mouse model. We also evaluated the effects of these peptides on oxidative stress and on the AMP-activated protein kinase (AMPK) signaling pathway, two major pathogenic factors of NASH. Seven‑week-old male C57BL/6 mice were fed a high-fat diet for 10weeks and administered water supplemented with 0.05%LRP, 0.20%LRP, 0.05%LQP, or 0.20%LQP (each n=5) or distilled water (control; n=5) adlibitum. Oxidative stress was evaluated by measuring the serum levels of diacron reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP). Hepatic expression of phosphorylated AMPK and phosphorylated acetyl-CoA carboxylase (ACC) were evaluated by immunoblotting. The result showed that non‑alcoholic fatty liver disease activity score was significantly decreased in all types of treatment. Serum d-ROM levels were significantly decreased in the 0.20% LRP group, but not in the 0.05% LRP, 0.05% LQP, and 0.20% LQP groups. Serum BAP levels were significantly increased in the 0.05% LRP and 0.20% LRP groups, but not in the 0.05% LQP and 0.20% LQP groups. Immunoblotting analysis revealed that the expression of phospho-AMPK was increased whereas that of phospho-ACC was decreased in the 0.20% LQP group. In conclusion, we demonstrated that both LRP and LQP alleviated the severity of NASH in a high-fat diet-induced NASH mouse model. In addition, we showed that LRP and LQP modulated oxidative stress and upregulated AMPK/ACC, respectively. Thus, LRP and LQP may constitute clinically applicable therapeutic agents for NASH.

Effect of startup circuit exercise on derivatives reactive oxygen metabolites, biological antioxidant potential levels and physical fitness of adolescents boys with intellectual disabilities.

The purpose of this study was to examine the effect of starup circuit exercise program on derivatives reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP) levels and physical fitness of adolescents with intellectual disabilities, and to sugesst exercise programs to promote the health and physical development of such adolescents. Twelve students with intellectual disabilities were divided into two groups; circuit exercise group (CE group: n=6; age, 14.83±0.98 years; height, 163.83±5.78 cm; body mass, 67.08±3.32 kg; %Fat, 25.68±2.42), control group (CON group: n=6; age: 15.00±0.63 years; height, 162.33±4.41 cm; body mass, 67.50±3.62 kg; %Fat, 26.96±2.06). The CE group performed the CE program 4 times a week over a 12-week period. The CON group maintained their activities of daily living. The following were measured before and after intervention: physical fitness by before and after the completion of the training programm, and were measured and blood samples were assessed. The results of the study indicate that the 12-week CE program increased significantly physical fitness (P<0.05). Furthermore, This study proved that the CE program improved physical fitness, and reduced the d-ROM levels, and increased the BAP levels of the adolescents with intellectual disabilities. Therefore, it may enhance the health and physical development of adolescents boys with intellectual disabilities.

Oxidative stress and inflammation are associated with physical frailty in patients with Alzheimer's disease.

Dementia is closely connected with frailty, and these two conditions are common in older adults. However, the biological mechanism that causes frailty in patients with Alzheimer's disease (AD) is not fully understood. We determined whether oxidative stress and inflammatory mechanisms could be associated with physical frailty in patients with AD. We studied 140 elderly outpatients with mild-to-moderate AD. Frailty status was determined according to the presence of the following five measurable characteristics: weight loss, exhaustion, low physical activity, slowness and weakness. We measured oxidative stress markers, including plasma levels of diacron reactive oxygen metabolite and biological anti-oxidant potential, endogenous plasma anti-oxidants, such as albumin, bilirubin and uric acid, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epiPGF2α (8-isoprostane), and inflammatory markers, including interleukin-6 and tumor necrosis factor-α. Among patients, 44 (31%) were non-frail, 62 (44%) were prefrail and 34 (24%) were frail. Frail and prefrail patients were older, more likely to be women and had more comorbid medical conditions than non-frail patients. Frail or prefrail patients showed significantly higher diacron reactive oxygen metabolite and lower biological anti-oxidant potential levels, a significant decrease in bilirubin, a significant increase in urinary 8-OHdG and 8-isoprostane levels, and a significantly higher interleukin-6 level, in contrast to non-frail patients. Physical frailty is common in old and female AD patients with comorbid medical diseases. The present results strongly suggest that oxidative stress and inflammation are involved in the pathophysiology of frailty status in individuals with AD. Geriatr Gerontol Int 2017; 17: 913-918.

Effect of Complex Training Program on Physical Fitness, Derivatives Reactive Oxygen Metabolite and Biological Antioxidant Potential Levels of Adolescents with Intellectual Disabilities

Aim: The purpose of this study was to examine the effects of complex exercise program on physical fitness, derivatives reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP) levels of adolescents with intellectual disabilities, and to sugesst exercise programs to promote the health and physical development of such adolescents. Methods: Sixteen students with intellectual disabilities were divided into 2 groups (Age: 13.37 ± 2.36 yrs, Height: 155.63 ± 9.72 cm, Weight: 63.24 ± 11.25 kg); exercise group (n=8), control group (n=8). The exercise group performed the complex exercise program 60 minutes a day, 3 times a week over a 12-week period. Then, the control group maintained their activities of daily living. Before and after the completion of the training program, and physical fitness were measured and blood samples were assessed. Results: The results of the study indicate that the 12-weeks complex exercise program increased significantly health- and skill-related. Furthermore, the d-ROM levels decreased more significantly in the exercise group than in the control group, and the BAP levels decreased after completion of the exercise program in the exercise group. Conclusion: This study proved that the complex exercise program improved physical fitness, and reduced the d-ROM levels of the adolescents with intellectual disabilities. Therefore, it may enhance the health and physical development of adolescents with intellectual disabilities.

Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis

Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)--compounds formed by the transformation of proteins--were evaluated as potential new markers of oxidative stress in this disease. This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; M age = 38 ± 13 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. Serum d-ROMs were elevated, and BAP decreased in HT patients compared with controls (p < 0.001), and the two parameters were inversely correlated (r = -0.211; p = 0.027), clearly indicating an enhanced oxidative stress. Furthermore, AGE levels were higher in HT patients (M = 223.18 AU/g prot) than in controls (M = 189.636 AU/g prot; p = 0.020) and inversely correlated with BAP levels (r = -0.196; p = 0.037). In uni- and multivariate analysis, serum antithyroperoxidase antibodies were the main predictors for d-ROMs (p = 0.006), BAP (p < 0.001), and AGEs (p = 0.014), irrespective of thyrotropin and/or free thyroxine values. No differences in AOPPs levels were found between patients and controls (p = 0.923). Oxidants are increased and antioxidants decreased in euthyroid HT patients. As a result, the oxidative/antioxidative balance is shifted toward the oxidative side. Moreover, this study reports on a possible significant involvement of AGEs in HT, thus contributing to a better definition of the redox homoeostasis dysregulation in HT.

A new method to assess oxidative stress in ART cycles

The role of oxidative stress (OS) in female reproduction is an understudied area for investigation. The aim of the study was to assess reactive oxygen species (ROS) levels both in follicular fluid (FF) and in serum samples of women undergoing IVF and to relate them to clinical outcomes. A total of 56 women were enrolled. From each patient a sample of serum and FF were collected at oocyte retrieval day and analyzed for OS, by measuring a class of reactive oxygen metabolites (ROMs) (dROMs test) and for biological anti-oxidant potential levels (BAP test). The data analyzed in serum and in FF were related to pregnancy outcomes. There was no significant relationship between d-ROMs and BAP levels in serum or FF GROUP A and B and the clinical parameters of prognosis of women: age, number of oocytes retrieved number of oocytes methaphase II, FSH, fertilization rate and cleavage rate, number of embryos transferred and embryo score. There was a positive association between systemic levels of OS measured in serum GROUP A and pregnancy outcomes (p = 0.007) suggesting that the evaluation of OS in FF needs more investigation about markers in follicular microenvironment in order to predict IVF success.

Age-dependency of the serum oxidative level in the senescence-accelerated mouse prone 8.

Systemic oxidative stress is considered to cause aging. In this study, to estimate the oxidative stress level in senescence-accelerated mouse prone 8 (SAMP8), we evaluated serum reactive oxygen species production and reduction capacity by measurement of Diacron-Reactive Oxygen Metabolites (d-ROM) and Biological Antioxidant Potential (BAP), respectively, with age. SAMP8 showed earlier increase of d-ROM value with age than SAM resistant 1 (SAMR1), the control strain. The BAP level was the highest in adult SAMP8, whereas SAMR1 presented the sustained BAP values between ages. These results indicate that oxidative stress in SAMP8 is higher than SAMR1. Our study is the first detailed report about d-ROM and BAP in SAMP8 and will provide useful fundamental data for future aging studies.

Biological Antioxidant Potential Negatively Correlates With Carotid Artery Intima-Media Thickness.

Oxidative stress is a crucial factor in the pathogenesis and development of cardiovascular disease. Recently, simplified methods for the detection of reactive oxygen species (ROS) using the derivatives of reactive oxygen metabolites (d-ROMs) test as an index of ROS products and the biological antioxidant potential (BAP) test as an index of antioxidant potential have been utilized. These methods are easy to perform, quick, inexpensive since they use small equipment, and provide reliable results compared with established oxidative stress and antioxidant markers. Because oxidative stress has been shown to represent the balance of production of ROS and antioxidant capacity, it is more appropriate to evaluate ROS and antioxidant capacity simultaneously. However, no study has examined the associations among d-ROMs, BAP values, and carotid artery intima-media thickness (IMT) concurrently. Therefore, we studied the associations among d-ROMs, BAP values, and the carotid artery IMT. Carotid artery IMT, blood pressure (BP), fasting circulating d-ROMs, BAP, glucose metabolism, lipid, and C-reactive protein levels were measured in 95 subjects (age: 49.5 ± 13.8 years; men: 41; women: 54), including 42 healthy subjects and 53 patients with hypertension, dyslipidemia, and diabetes mellitus who were not on medication. The results of multiple regression analysis revealed that dependent carotid artery IMT determinants remained significantly associated with age, systolic BP, total cholesterol, and BAP, whereas dependent BAP determinants remained significantly associated with body mass index and carotid artery IMT. BAP was strongly correlated with carotid artery IMT in our cohort. Our results suggest that BAP may be a useful risk marker for carotid atherosclerosis.

Influence of green tea catechins on oxidative stress metabolites at rest and during exercise in healthy humans

ObjectivesThe aim of this study was to investigate the effects of green tea catechins (GTC) on oxidative stress metabolites in healthy individuals while at rest and during exercise. The effects investigated included response to fat metabolism, blood lactate concentrations, and rating of perceived exertion. MethodsIn a paralleled, crossover, randomized controlled study, 16 trained male gymnastic students were randomly divided into two groups. The rest group (n = 8; GTC-NEX) received a single dose of 780 mg GTC with water but no exercise; the exercise group (n = 8; GTC-EX) received a similar dose of GTC but were instructed to exercise. This was followed by a crossover study with similar exercise regime as a placebo group (PL-EX) that received water only. Blood samples were collected at baseline and after 60 and 120 min of GTC intake. Oxidative stress blood biomarkers using the diacron reactive oxygen metabolite (d-ROMs) and biological antioxidant potential (BAP) tests; urinary 8-hydroxydeoxyguanosine (8-OHdG); 8-OHdG/creatinine; and blood lactate concentrations were analyzed. During the cycle ergometer exercise, volume of maximal oxygen uptake, volume of oxygen consumption, volume of carbon dioxide, and respiratory exchange ratio were measured from a sample of respiratory breath gas collected during low, moderate, and high intensity exercising, and the amount of fat burning and sugar consumption were calculated. Analysis of variance was used to determine statistical significance (P < 0.05) between and among the groups. ResultsLevels of postexercise oxidative stress metabolites BAP and d-ROMs were found significant (P < 0.0001) in the PL-EX and GTC-EX groups, and returned to pre-exercise levels after the recovery period. Levels of d-ROMs showed no significant difference from baseline upon GTC intake followed by resting and a resting recovery period in the GTC-NEX group. BAP levels were significant upon GTC intake followed by resting (P = 0.04), and after a resting recovery period (P = 0.0006) in the GTC-NEX group. Urinary 8-OHdG levels were significant (P < 0.005) for all groups after the recovery period. A significant difference was noticed between the ratios of resting BAP to d-ROMs and exercise-induced BAP to d-ROMs (P = 0.022) after 60 min of GTC intake, as well as resting 8-OHdG and exercise-induced 8-OHdG levels (P = 0.004) after the recovery period. Oxidative potentials were higher when exercise was performed at low to moderate intensity, accompanied by lower blood lactate concentration and higher amounts of fat oxidation. ConclusionsThe results of the present study indicate that single-dose consumption of GTC influences oxidative stress biomarkers when compared between the GTC-NEX and GTC-EX groups, which could be beneficial for oxidative metabolism at rest and during exercise, possibly through the catechol-O-methyltransferase mechanism that is most often cited in previous studies.

Correlation between Systemic Oxidative Stress and Intraocular Pressure Level.

BackgroundThe involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. We reported previously that the level of systemic antioxidative capacity is lower in patients with open-angle glaucoma than controls without glaucoma. Here, we assessed the correlation between IOP and systemic levels of prooxidants and antioxidants by analyzing the blood biochemistry in patients with glaucoma.MethodsPeripheral blood samples were collected from Japanese patients with primary open-angle glaucoma (n = 206), exfoliation syndrome (n = 199), and controls (n = 126). Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. To test the possible effect of oxidative stress on IOP levels, the patients were classified into one of four groups (Q1, Q2, Q3, and Q4, with Q1 having the lowest IOP) based on the quartile value of IOP. For this classification, the known highest IOP value in both the right and left eyes was regarded as each subject’s IOP. For comparisons among the IOP groups, the differences were calculated using one-way analysis of variance followed by post-hoc unpaired t-tests. To adjust for differences in demographic characteristic distributions, the dROM, BAP, and SH test values were compared among the IOP groups using multiple logistic regression analysis; the odds ratio (OR) of each variable was calculated with the Q1 group as the reference.ResultsThe dROM and the SH levels did not differ significantly (p = 0.6704 and p = 0.6376, respectively) among the four IOP groups. The BAP levels differed significantly (p = 0.0115) among the four IOP groups; the value was significantly lower in the Q4 group (1,932 μmol/L) compared with the Q1 (2,023 μmol/L, p = 0.0042) and Q2 (2,003 μmol/L, p = 0.0302) groups and significantly lower in the Q3 group (1,948 μmol/L) than the Q1 (p = 0.0174) group. After adjustment for differences in various demographic characteristics, lower BAP values were significantly associated with the classification into higher IOP groups (Q3 group, p = 0.0261 and OR = 0.06/range; Q4 group, p = 0.0018 and OR = 0.04/range). The dROM and SH values did not reach significance in any comparisons.ConclusionsLower systemic antioxidant capacity measured by ferric-reducing activity is involved in the pathogenesis of open-angle glaucoma via its roles in IOP elevation.

Peripheral Oxidative Stress Markers in Individuals with Alzheimer's Disease with or without Cerebrovascular Disease

To the Editor: Growing evidence suggests that oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD).1, 2 A previous meta-analysis reported that a number of studies showed high lipid peroxidation marker, protein oxidation marker, and deoxyribonucleic acid and ribonucleic acid oxidation marker levels and low antioxidant levels in individuals with AD.3 Extensive lines of evidence support the role of oxidative injury in the pathogenesis of stroke and other vascular disease.4 Cerebrovascular disease (CVD), such as lacunes and white matter lesions, are common in elderly adults with AD. Although there may be some differences in oxidative damage between individuals with AD with and without CVD, there is a lack of studies examining biomarkers of oxidative damage in these individuals. In the present study, differences in peripheral oxidative stress markers between individuals with CVD with and without AD were determined, and correlations between biomarkers of oxidative damage and cognitive impairment were investigated. Sixty-nine individuals with AD without CVD (AD group) and 36 individuals with AD and CVD (AD + CVD group) were enrolled from a memory clinic. Individuals with AD had to meet the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria5 for a diagnosis of probable AD. AD with CVD was defined as typical AD associated with clinical and radiological evidence of CVD in the deep gray and white matter.6 In addition, 40 elderly individuals with no signs of cognitive impairment or CVD in the clinic were randomly chosen and used as a control group. Individuals with malignancies, severe cardiac or pulmonary disease, liver cirrhosis, renal failure, infectious disease, or disease requiring immunosuppressive therapy; current smokers; and individuals taking antioxidant supplements or vitamins were excluded. Cognitive function was assessed using the Mini-Mental State Examination (MMSE).7 Diacron reactive oxygen metabolite (dROM) levels, reflecting the amount of organic hydroperoxide, and biological antioxidant potential (BAP), measuring the ferric reducing ability of blood plasma, were measured using a free radical analyzer system (FRAS 4, Wismerll Company Ltd., Tokyo, Japan).8, 9 All analyses were performed within 48 hours of venous blood collection. Statistical analysis was conducted using Student t-tests, the chi-square test, analysis of covariance (ANCOVA), and the Spearman rank correlation test. Table 1 show participant characteristics and peripheral oxidative stress markers. The group with AD was significantly younger than the control group and had significantly more women than the control and AD + CVD groups. No significant differences in education and comorbidities such as hypertension, diabetes mellitus, dyslipidemia, and heart disease were found between the three groups. The AD and AD + CVD groups had significantly lower MMSE scores than the control group, but no significant differences in MMSE score and dementia duration were found between the AD and AD + CVD groups. ANCOVA, taking into account age and sex as covariates, showed that dROM levels were significantly higher in the AD group than in the control group and that BAP levels were significantly lower in the AD + CVD group than in the control and AD groups. As a result, BAP/dROM ratios were significantly lower in the AD and AD + CVD groups than in the control group and significantly lower in the AD + CVD group than in the AD group. MMSE scores significantly and negatively correlated with dROM levels (correlation coefficient (r) = −0.231, P = .02) and significantly and positively correlated with BAP/dROM ratios (r = 0.224, P = .02) but did not correlate significantly with BAP levels in participants with AD and AD + CVD. Oxidative damage was involved in the pathophysiology of the AD and AD + CVD groups and correlated with cognitive impairment. In particular, the AD + CVD group had greater abnormalities of oxidative stress markers, including the antioxidant defense system, than the AD group. These results suggest that intervention for oxidative stress may be appropriate for the inhibition of progression and prevention of cognitive impairment in individuals with AD, particularly for those who also have CVD. Although there may be some differences in oxidative damage between the central nervous system and peripheral tissue, measurements of peripheral oxidative stress markers may be useful for the assessment of disease progression. Conflict of Interest: The authors have no financial disclosures to declare. There are no conflicts of interest regarding this letter. Author Contributions: Hanyu, Iwamoto: study concept and design, acquisition of participants and data, data analysis and interpretation, preparation of manuscript. Hatanaka, Hirose, Fukasawa, Namioka: acquisition of patients, data analysis. Sponsor's Role: None.

Effects of Febuxostat on Oxidative Stress

PurposeWe previously examined factors that affect the measured derivatives of reactive oxygen metabolites (d-ROMs), an indicator of reactive oxygen species production, and biological antioxidant potential (BAP), an indicator of antioxidant capacity, in typical health checkup examinees and reported the usefulness of measuring both indicators simultaneously. In addition, a positive correlation reportedly exists between d-ROMs and the visceral fat area measured by using computed tomography. A recent study of the relationship between uric acid levels and various obesity-related factors found that visceral fat was the factor most strongly related to uric acid levels. Uric acid is itself a potent endogenous antioxidant, but because reactive oxygen species are produced during uric acid generation, it is suggested that uric acid may have opposing effects. The objective of this study was to analyze the effect of febuxostat, a novel xanthine oxidase inhibitor, on oxidative stress. MethodsStudy subjects were 43 hyperuricemia outpatients receiving care in the internal medicine department of our institution. The subjects were divided into a new administration group (29 patients) and a switched administration group (14 patients); the latter were allopurinol-treated patients with hyperuricemia who were switched to febuxostat. In addition to measuring the patients’ uric acid and creatinine levels and estimated glomerular filtration rate before and after treatment, their d-ROMs and BAP as well as the BAP/d-ROMs ratio were also measured. FindingsBoth groups exhibited significant decreases in uric acid levels, as well as significant decreases in d-ROMs and BAP. No significant changes were observed in the BAP/dROMs ratio or renal function, including creatinine levels and estimated glomerular filtration rate. ImplicationsFebuxostat could significantly reduce d-ROMs. However, BAP levels were also significantly reduced concurrently. No changes were observed in the BAP/d-ROMs ratios. This regulatory mechanism is believed to have counteracted changes in the in vivo oxidative stress balance caused by febuxostat administration.

Influence of smoking on perioperative oxidative stress after pulmonary resection.

We herein investigated the influence of smoking on changes in the levels of perioperative oxidative stress after pulmonary resection. A total of 31 patients with primary lung cancer who underwent curative pulmonary lobectomy were analyzed prospectively. The degree of perioperative oxidative stress was evaluated based on the serum levels of derivatives of reactive oxygen metabolites (d-ROM) and biological antioxidant potential (BAP). The patients were divided into two groups: group A (smoking < 40 pack-years) and group B (smoking ≥ 40 pack-years). The d-ROM and BAP measurements were obtained preoperatively, postoperatively and on the first, second, third and fifth postoperative days. In all 31 cases, the d-ROM values were higher on the third and fifth postoperative days than preoperatively. The extent of change in the d-ROM levels was greater in group A than in group B on the second, third and fifth postoperative days (1.05 ± 0.159 vs. 0.920 ± 0.205, p = 0.008; 1.20 ± 0.233 vs. 1.02 ± 0.186, p = 0.032; 1.34 ± 0.228 vs. 1.07 ± 0.200, p = 0.003, respectively). In contrast, there were no significant differences in the BAP values. The maximum increase in the d-ROM level and decrease in the BAP level negatively correlated with the amount of smoking (|r| = 0.428, p = 0.016 and |r| = 0.357. p = 0.049, respectively). Surgical stress associated with pulmonary lobectomy induces oxidative stress. In addition, smoking reduces the oxidative stress reaction, and the degree of this change is correlated with the amount of smoking.

Video-assisted thoracic surgery attenuates perioperative oxidative stress response in lung cancer patients: a preliminary study

Objectives: Reactive oxygen species (ROS) function as key metabolites that can impair biological processes. The aim of this preliminary study was to assess the perioperative oxidative changes in lung cancer surgery. Methods: We measured the levels of blood hydroperoxides, a type of ROS, as an index of oxidative injury to cellular components, as well as the plasma ferric-reducing ability as an index of total antioxidant potential in 32 lung cancer patients. Hydroperoxides were measured by the levels of diacron reactive oxygen metabolites (d-ROMs). The antioxidant potential was determined by the biological antioxidant potential (BAP), which represents the levels of endogenous antioxidant enzymes. Results: Lung cancer patients had slightly affected oxidative stress before surgery. The d-ROM and BAP levels after surgery and were significantly decreased than before surgery (p< 0.001) and the levels recovered preoperatively at third postoperative day. The d-ROM level in video-assisted surgery group (n=17) was significantly decreased than those in thoracotomy group (n=15) at third and seventh post-operative day (p < 0.001, and < 0.02). Conclusions: Lung cancer patients had already exposed oxidative stress before surgery and surgical intervention also generates large amounts of ROS. Video-assisted thoracic surgery can reduce the ROS compared to the standard thoractomy. ACTA MEDICA NAGASAKIENSIA 59: 19−25, 2014

PACAP38 suppresses cortical damage in mice with traumatic brain injury by enhancing antioxidant activity.

The production of reactive oxygen species (ROS) and the resulting oxidative stress in mice in response to a controlled cortical impact (CCI) are typical exacerbating factors associated with traumatic brain injury (TBI). Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a multifunctional peptide that has been shown to exhibit neuroprotective effects in response to a diverse range of injuries to neuronal cells. We recently reported that PACAP38 might regulate oxidative stress in mice. The aim of the present study was to determine whether PACAP38 exerts neuroprotective effects by regulating oxidative stress in mice with TBI. Reactive oxidative metabolites (ROMs) and biological antioxidant potential (BAP) were measured in male C57Bl/6 mice before and 3, 4, and 24 h after CCI. PACAP38 was administered intravenously immediately following CCI, and immunostaining for the oxidative stress indicator nitrotyrosine (NT), and for neuronal death as an indicator of the area affected by TBI, was measured 24 h later. Western blot experiments to determine antioxidant activity [as indicated by superoxide dismutase-2 (SOD-2) and glutathione peroxidase 1 (GPx-1)] in the neocortical region were also performed 3 h post-CCI. Results showed that plasma BAP and ROM levels were dramatically increased 3 h after CCI. PACAP38 suppressed the extent of TBI and NT-positive regions 24 h after CCI, and increased SOD-2 and GPx-1 levels in both hemispheres. Taken together, these results suggest that increasing antioxidant might be involving in the neuroprotective effect of PACAP38 in mice subjected to a CCI.

Changes in diacron‐reactive oxygen metabolites and biological antioxidant potential in maternal serum during pregnancy (910.6)

The objective of this research is to identify changes in serum oxidative stress and antioxidant levels during normal pregnancy using the diacron‐reactive oxygen metabolites (d‐ROMs) test and biological antioxidant potential (BAP) test. This cross‐sectional study enrolled 126 pregnant women who attended a maternity clinic in Japan. Healthy, non‐pregnant women of reproductive age were recruited as controls. Serum d‐ROMs and BAP were measured within 72 hours using a Free Radical Elective Evaluator. Subjects were divided into five groups: 8‐13 w (n=15), 14‐27 w (n=42), 28‐32 w (n=31), 36‐37 w (n=38), and control (n=7). The pregnant women’s average d‐ROMs and BAP levels were 499.4 ± 99.0 U.CARR and 1977.1 ± 179.3 μmol/l, respectively. The d‐ROMs level in 36‐37 w group increased significantly compared with the control, 8‐13 w and 14‐27 w groups (p=0.000, p=0.009, p=0.006). The BAP level in the 36‐37 w group decreased significantly compared with all other groups (p=0.000). These results suggest that oxidative stress increases and antioxidant power decreases throughout the gestational period, and that the pro‐oxidant antioxidant balance is disturbed most at the end of gestation.Grant Funding Source: KAKENHI（Grants‐in‐Aid for Scientific Research)