Effects of parenteral lipid infusion on DNA damage in very low birth weight infants

Very low birth weight (VLBW) infants are known to have poorly developed antioxidant system and may be at increased risk for radical damage. Previous studies have reported higher levels of lipid peroxide products in lipid emulsion used for parenteral nutrition. To examine the direct effects of parenteral lipid infusion on DNA damage in VLBW infants, we measured urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in VLBW infants before, during, and after the parenteral lipid infusion. In both the lipid-infused and lipid-free groups, urinary 8-OHdG excretion levels at 14 days old were significantly (p < 0.01) lower than those at 2 and 7 days old. However, there were no significant differences in urinary 8-OHdG excretion levels between the lipid-infused and lipid-free groups at 2, 7, and 14 days old. Our results suggest that parenteral lipid infusion does not cause oxidative DNA damage, but irrespective of the infusion DNA damage during the first week of life is enhanced when compared with 14 days after birth in VLBW infants.     

Oxidative stress in very low birth weight infants as measured by urinary 8-OHdG

Very low birth weight (VLBW) infants can be subjected to oxidative stress in the course of intensive care. We measured 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative stress, and estimated the degree of oxidative stress in such infants. We also examined if the administered oxygen was related to oxidative stress. Urine samples of 50 Japanese VLBW infants [birth weights: 956.3+/-277.6g, and gestational ages: 28.0+/-2.6 weeks (mean +/- SD)] were collected on various postnatal days and 8-OHdG levels were determined using an ELISA kit. Sixteen term infants served as normal controls. As body weights at sampling increased, the average levels of urinary 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants under 1000g, 29.5+/-16.4 micromol/mol creatinine (n = 24); 1000-1500g, 23.8+/-14.9 (n = 12); over 1500g, 16.1+/-8.5 (n = 14); and control, 10.9+/-7.2 (n = 16). Significant differences were found between <1000g group and > or = 1500g group (p = 0.0030), <1000g group and control (p < 0.0001), and 1000-1500g group and control (p = 0.0108). Also as postconceptional age at sampling increased, the average levels of 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants before 252 days (36 weeks) of postconception: 27.4+/-15.5 micromol/mol creatinine (n = 34); after 252 days, 18.2+/-12.5 (n = 16). Differences between <252 days group and control (p < 0.0001), and <252 days group and > or = 252 days groups (p = 0.0253) were statistically significant. Among the three groups based on ambient oxygen concentration (21%, 22-29%, and > or = 30%) there was no significant difference (p = 0.417). The more premature the infants were, the more intense was the oxidative stress, hence, it is the prematurity rather than the administered oxygen which causes oxidative stress in VLBW infants. Drury et al. ["Urinary 8-hydroxydeoxyguanosine in infants and children" Free Radic. Res. 28 (1998) 423-4281 measured urinary 8-OHdG of 28 infants (24-40 weeks gestation) and found no gestation or birthweight related differences. This discrepancy seemed to be because of difference in birth weights and sampling period of the subjects.     

Urinary 8-Hydroxydeoxyguanosine in Infants and Children

Several diseases of prematurity are thought to be related to oxidative injury and many of the available markers are unsatisfactory. An assay was developed using HPLC with electrochemical detection for the quantitation of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a proposed indicator for oxygen-derived free radical injury to DNA in preterm infants.

A median value of 3.79 pmol/mol creatinine was obtained for normal children (2–15 years old, n = 14). Urinary 8-OHdG excretion in neonates ranged from 0–99μmol/mol creatinine. There were no gestation or birthweight related differences in urinary 8-OHdG, and no correlation with urinary malondialdehyde. Mean 8-OHdG excretion increased with postnatal age (r= 0.80, p < 0.0001, n = 15), mirroring the growth velocity curve. These changes could also be due to changes in the activity of the enzyme responsible for 8-OHdG excision.

Urinary 8-OHdG levels are unlikely to accurately reflect oxygen derived free radical activity given the strength of the relationship with growth.     

Urinary excretion of 8-hydroxydeoxyguanosine and malondialdehyde after high dose radiochemotherapy preceding stem cell transplantation

The urinary excretion of the hydroxylated DNA base 8-hydroxydeoxyguanosine (8-OHdG) and the lipid peroxidation product malondialdehyde (MDA) was monitored in 11 patients with hematological malignancies undergoing total body irradiation and high-dose chemotherapy preceding bone marrow transplantation. Nine patients showed a prompt increase in urinary 8-OHdG (8-25 times the initial baseline level) on days 0-7 after irradiation onset; the excretion then decreased during the aplastic period and increased again when engraftment took place (in 7 patients). A significant positive correlation was found between urinary 8-OHdG and whole blood leukocyte count, both on day 5 (p =.04, r =.72) and on day 22 (p =.009, r =.80) after irradiation onset. One patient who lacked the first peak of 8-OHdG excretion showed low blood leukocyte counts (less than 2 x 10(9)/l) before therapy onset; this patient, however, later had a successful engraftment and then also showed considerable increases in both 8-OHdG excretion and leukocyte count. These observations suggest leukocytes play a part in the excretion of 8-OHdG after conditioning therapy preceding bone marrow transplantation. As opposed to the biphasic 8-OHdG excretion, the excretion of MDA showed a single peak appearing on days 11-19 after radiochemotherapy onset, i.e., during the period in which the patients suffered from cytopenia, mucositis, and other side effects of the treatment. It is suggested, therefore, that these clinical manifestations are associated with increased lipid peroxidation. Altogether, these findings illustrate the utility of serial urinary samples for monitoring oxidative stress due to conditioning therapy in clinical practice. They also demonstrate that different oxidative stress markers may behave quite differently regarding their appearance in the urine after whole-body oxidative stress.     

Urinary Levels of 8-Hydroxydeoxyguanosine as a Marker of Oxidative Damage in Road Cycling

We have determined the urinary 8-hydroxydeoxyguanosine (8-OHdG) levels of eight professional cyclists during a 4-day and a 3-week stage races. Monitoring of heart rates was used to establish zones corresponding to different intensities of exercise. The urinary 8-OHdG excretion, expressed by body weight, increased significantly in the first day or the first week of each race, respectively, and did not show further increases thereafter. Maximum 8-OHdG levels were reached in parallel to longer times spent at high intensities of exercise. Urinary excretion of creatinine increased with exercise, and changes in 8-OHdG levels were not detected when corrected by creatinine excretion. Serum glutathione concentrations did not change significantly at any point during exercise. We conclude that road cycling courses with an oxidative damage to DNA, which is sustained as long as the exercise is repeated. Both adaptation of antioxidant defenses and a decreased capacity to maintain a high intensity of effort may contribute to explain the absence of progressive increases in 8-OHdG excretion. The results of this study also confirm that the correction procedure using the amount of creatinine excreted should not be used when studying effects of exercise on urinary 8-OHdG.     

Urinary levels of 8-hydroxydeoxyguanosine as a marker of oxidative damage in road cycling

We have determined the urinary 8-hydroxydeoxyguanosine (8-OHdG) levels of eight professional cyclists during a 4-day and a 3-week stage races. Monitoring of heart rates was used to establish zones corresponding to different intensities of exercise. The urinary 8-OHdG excretion, expressed by body weight, increased significantly in the first day or the first week of each race, respectively, and did not show further increases thereafter. Maximum 8-OHdG levels were reached in parallel to longer times spent at high intensities of exercise. Urinary excretion of creatinine increased with exercise, and changes in 8-OHdG levels were not detected when corrected by creatinine excretion. Serum glutathione concentrations did not change significantly at any point during exercise. We conclude that road cycling courses with an oxidative damage to DNA, which is sustained as long as the exercise is repeated. Both adaptation of antioxidant defenses and a decreased capacity to maintain a high intensity of effort may contribute to explain the absence of progressive increases in 8-OHdG excretion. The results of this study also confirm that the correction procedure using the amount of creatinine excreted should not be used when studying effects of exercise on urinary 8-OHdG.     

Urinary excretion of 8-hydroxy-2'-deoxyguanosine measured by high-performance liquid chromatography with electrochemical detection

There is good evidence that oxidative DNA damage permanently occurs in living cells. The oxidative DNA damage product 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the predominant forms of radical-induced lesions to DNA, and has therefore been widely used as a biomarker for oxidative stress, either in cellular DNA or as DNA repair product in urine. In this paper we describe the use of a high-performance liquid chromatographic procedure with electrochemical detection for the measurement of urinary 8-OHdG. Our study has addressed the questions (i) of baseline urinary levels of 8-OHdG in spot urine and 24-h urine, (ii) of inter- and intra-individual variation of this biomarker, and (iii) of confounding factors for the excretion of 8-OHdG. No significant difference between the mean group levels of 8-OHdG/creatinine in spot urine (2.03+/-1.21 micromol/mol, n=148) and in 24-h urine (1.86+/-1.09 micromol/mol, n=67) was observed. However, when only 24-h urine was used for analysis, 8-OHdG was found to be statistically significantly higher in smokers. By multiple linear regression analysis, urinary creatinine was identified as the only predictor of 8-OHdG/24 h (r(p)=0.33, P=0.007). High intra-individual coefficients of variation of 8-OHdG/24 h were observed in two healthy subjects over a period of 10 consecutive days (37 and 57%, respectively), indicating that the intra-individual fluctuation of urinary 8-OHdG has so far been underestimated. Therefore, we suggest that single values of 8-OHdG should be considered with caution, in particular in small study groups and when spot urine is used.     

Effects of supplemental oxygen on urinary 8-hydroxy-2’-deoxyguanosine levels in extremely low birth weight infants

Abstract

As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2’-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 ± 6.9 vs. 5.6 ± 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.     

Longitudinal study of urinary 8-hydroxy-2'-deoxyguanosine excretion in healthy adults

Numerous studies have investigated the urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for the assessment of oxidative DNA damage in humans. In this study, we performed six consecutive series of measurement of urinary levels of 8-OHdG in 68 healthy probands, in order to provide information on the intra- and inter-individual variability of 8-OHdG and to estimate the influence of smoking, age, sex, body weight and body mass index (BMI) on the excretion of 8-OHdG. The intraindividual coefficient of variation (CV) of urinary 8-OHdG/24h ranged from 0.18 to 1.06 (mean CV=0.48). Women excreted significantly lower amounts of 8-OHdG/24h than men, but the difference lost its significance when the body weight or urinary creatinine were used as covariates. By multiple linear regression analysis significant correlations between the mean individual levels of 8-OHdG/24h excretion and urinary creatinine (r_p = 0.61), and cotinine (r_p = 0.27) have been observed, whereas no statistically significant effect of age, body weight and BMI was found. The 8-OHdG/creatinine ratio was found to be significantly increased in 23 smokers (1.95 ± 0.40 μmol/mol) opposed to 45 non-smoking probands (1.62 ± 0.50 μmol/mol), which is in good agreement with previously published data. No effect of passive smoking on the excretion of 8-OHdG was found. From our data we conclude that the intraindividual variability of urinary 8-OHdG excretion has been underestimated so far, indicating that values of 8-OHdG measured by single spot monitoring are not representative for individual base levels.     

Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise

Rahimi, R. Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. J Strength Cond Res 25(12): 3448-3455, 2011-Creatine (Cr), or methyl guanidine-acetic acid, can be either ingested from exogenous sources, such as fish or meat, or produced endogenously by the body, primarily in the liver. It is used as an ergogenic aid to improve muscle mass, strength, and endurance. Heretofore, Cr's positive therapeutic benefits in various oxidative stress-associated diseases have been reported in the literature and, recently, Cr has also been shown to exert direct antioxidant effects. Therefore, the purpose of this study was to investigate the effects of an acute bout of resistance exercise (RE) on oxidative stress response and oxidative DNA damage in male athletes and whether supplementation with Cr could negate any observed differences. Twenty-seven resistance-trained men were randomly divided into a Cr supplementation group (the Cr group [21.6 ± 3.6 years], taking 4 × 5 g Cr monohydrate per day) or a placebo (PL) supplementation group (the PL group [21.2 ± 3.2 years], taking 4 × 5 g maltodextrin per day). A double-blind research design was employed for a 7-day supplementation period. Before and after the seventh day of supplementation, the subjects performed an RE protocol (7 sets of 4 exercises using 60-90 1 repetition maximum) in the flat pyramid loading pattern. Blood and urine samples taken before, immediately, and 24-hour postexercise were analyzed for plasma malondialdehyde (MDA) and urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion. Before the supplementation period, a significant increase in the urinary 8-OHdG excretion and plasma MDA levels was observed after RE. The Cr supplementation induces a significant increase in athletics performance, and it attenuated the changes observed in the urinary 8-OHdG excretion and plasma MDA. These results indicate that Cr supplementation reduced oxidative DNA damage and lipid peroxidation induced by a single bout of RE.     

Association between M/L55-polymorphism of paraoxonase enzyme and oxidative DNA damage in patients with type 2 diabetes mellitus and in control subjects

The paraoxonase enzyme (PON) gene polymorphism causes a change of methionine (M-allele) to leucine (L-allele). PON may reduce low density lipoprotein oxidation and prevent atherosclerosis. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive index of oxidative DNA damage. We have studied the association between the PON genotypes and the urinary excretion of 8-OHdG. The study population consisted of 93 Finnish type 2 diabetes patients and 106 non-diabetic control subjects. The 24-h excretion of 8-OHdG was significantly higher in diabetic patients than in control subjects (P<0.001). In control subjects, the ratio of the 8-OHdG/glomerular filtration rate increased in order of genotype from MM to ML to LL (P<0.0412). These results suggest that lipid peroxidation may have an effect on DNA oxidation.     

Fluidity and oxidative stress in erythrocytes from very low birth weight infants during their first 7 days of life

Objective: To study the evolution of lipid peroxidation, enzymatic antioxidants response, lipid profile and membrane fluidity in erythrocytes from very low birth weight (VLBW) infants during their first 7 days of extra-uterine life.

Study design: One hundred and twenty infants were selected and divided in two groups according to their weight and gestational age. Hydroperoxides, fatty-acid profile, fluidity (DPH and TMA-DPH) and catalase, SOD and GPx activities were measured in erythrocytes.

Results: VLBW group showed higher concentration of hydroperoxides and lower membrane fluidity during the first 72 h, lower SOD activity during the first 3 h and higher GPx activity during the first 7 days of life. Also, this group showed lower n-3 polyunsaturated fatty-acids percentage with respect to the term group.

Conclusion: Erythrocytes from VLBW infants showed higher oxidative damage and lower fluidity in their membranes, at least during the first 3 days of extra-uterine life, which may cause alterations in their functions and flexibility.     

Fluidity and oxidative stress in erythrocytes from very low birth weight infants during their first 7 days of life

Objective: To study the evolution of lipid peroxidation, enzymatic antioxidants response, lipid profile and membrane fluidity in erythrocytes from very low birth weight (VLBW) infants during their first 7 days of extra-uterine life.

Study design: One hundred and twenty infants were selected and divided in two groups according to their weight and gestational age. Hydroperoxides, fatty-acid profile, fluidity (DPH and TMA-DPH) and catalase, SOD and GPx activities were measured in erythrocytes.

Results: VLBW group showed higher concentration of hydroperoxides and lower membrane fluidity during the first 72 h, lower SOD activity during the first 3 h and higher GPx activity during the first 7 days of life. Also, this group showed lower n-3 polyunsaturated fatty-acids percentage with respect to the term group.

Conclusion: Erythrocytes from VLBW infants showed higher oxidative damage and lower fluidity in their membranes, at least during the first 3 days of extra-uterine life, which may cause alterations in their functions and flexibility.     

Effect of docosahexaenoic acid and eicosapentaenoic acid supplementation on oxidative stress levels during pregnancy

Docosahexaenoic acid (DHA) is an indispensable component of cell membranes with high requirements during pregnancy. DHA supplementation is thought to enhance oxidative stress because of increased likelihood of lipid peroxidation. We estimated the oxidative stress levels in two groups of pregnant women who received daily supply of required vitamins with (n = 23) or without (n = 23) 500 mg of DHA and 150 mg of eicosapentaenoic acid (EPA) from 20 weeks of gestation to the time of delivery. Urinary excretions of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage and of malondialdehyde (MDA), a marker of lipid peroxidation, were measured at 20, 30 weeks and at the time of delivery. Urinary MDA excretion remained unchanged throughout the study period in both groups. Urinary 8-OHdG excretion at delivery was significantly higher than at 20 and 30 weeks (p < 0.05), but there were no group differences at the three time points. There were no differences between the two groups in plasma a-tocopherol levels. We conclude that under the conditions studied, a daily supplementation of 500 mg DHA and 150 mg EPA with vitamins to pregnant women did not enhance lipid peroxidation or oxidative DNA damage.     

Oxidative DNA damage (8-hydroxydeoxyguanosine) and body iron status: a study on 2507 healthy people

To clarify the relationship of oxidative stress and body iron status, we detected urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of oxidative DNA damage, and measured serum ferritin and total iron-binding capacity (TIBC), both reflecting body iron store, on 2507 healthy people aged between 22 and 89 years (males, 1253; females, 1254). The urinary 8-OHdG excretion of males showed almost no change with age, but the excretion of premenopausal females was lower than that of males, whereas postmenopausal females excreted significantly more than males. The values of serum ferritin showed no remarkable change with age in males, but increased gradually in postmenopausal females without iron loss due to bleeding, although the males' values remained higher than those of females at all ages (p<.05). On the other hand, the values of TIBC remained within the narrow limits in males, regardless of age, whereas those of females always stayed at a higher level than the males (p<.05). Conclusively, urinary 8-OHdG correlated with serum ferritin positively and with TIBC inversely, which suggested that body iron status would control the generation of 8-OHdG in vivo. After all, the increase of urinary 8-OHdG excretion in postmenopausal females may be caused by the decrease of body iron loss.     

Evaluation of a Multi-parameter Biomarker Set for Oxidative Damage in Man: Increased Urinary Excretion of Lipid,Protein and DNA Oxidation Products after One Hour of Exercise

The objective of the present study was to evaluate a comprehensive set of urinary biomarkers for oxidative damage to lipids, proteins and DNA, in man. Eighteen moderately trained males (mean age 24.6±0.7) exercised 60?min at 70% of maximal O₂ uptake on a cycle ergometer. Urine fractions for 12?h were collected 1 day before, and for 3 consecutive days after exercise.

As biomarkers of lipid peroxidation, 8 aldehydes (i.e. propanal, butanal, pentanal, hexanal, heptanal, octanal, nonanal and malondialdehyde—MDA)and acetone were analyzed in urines by gas chromatography with electron capture detection (GC-ECD). As a biomarker of protein oxidation, o,o′-dityrosine was analyzed in urine samples by a recently developed isotope dilution HPLC-atmospheric pressure chemical ionization (APCI)-tandem-mass spectrometry (HPLC-APCI-MS/MS) methodology. As a biomarker of oxidative DNA damage, urinary excretion of 8-hydroxy-2′-deoxyguanosine (8-OHdG) was measured by an ELISA method.

On the day of exercise, significant increases were observed in urinary excretions of acetone (?p<0.025, n=18) and butanal (?p<0.01, n=18) in the 12?h daytime fractions compared to the daytime fraction before exercise. The urinary acetone excretion was also significantly (?p<0.05) increased on the 1st day after exercise. Octanal and nonanal were increased in the daytime urine fraction on the 2nd day after exercise. However, these increases were of borderline significance (?p=0.09 and p=0.07, respectively).

Significantly elevated urinary o,o′-dityrosine amounts were observed in the daytime fraction on the day of exercise (?p<0.025) and on the 1st day after exercise (?p=0.07) compared to the before exercise daytime fraction.

Excretion of urinary 8-OHdG was statistically significantly increased in the daytime fractions on the day of exercise (?p=0.07) and on the 1st day after exercise (?p<0.025) compared to before exercise daytime fraction.

Increases in urinary excretions of acetone, propanal, pentanal, MDA and 8-OHdG significantly correlated with training status (hours of exercise/week) of the volunteers, while o,o′-dityrosine did not.

To our knowledge, the present study is the first to evaluate a multi-parameter non-invasive biomarker set for damage to three main cellular targets of ROS. It shows that 1?h of exercise may already induce oxidative damage in moderately trained individuals and that the chosen urinary biomarkers are sensitive enough to monitor such damage.     

Analysis of 8-hydroxydeoxyguanosine among workers exposed to diesel particulate exhaust: comparison with urinary metabolites and PAH air monitoring

Oxidative DNA damage and repair, as measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and DNA samples were studied in association with work-related diesel exhaust exposure among garage and waste collection workers. Seasonal variations of the urinary 8-OHdG levels in pre- and two post-workshift urine samples of 29 exposed workers and 36 control persons were evaluated. The mean±SE levels of post-workshift 8-OHdG (μmol/mol crea) were 1.52±0.44 in winter and 1.61±0.33 in summer for the exposed workers, and 1.56±0.61 in winter and 1.43±0.49 in summer for the controls, respectively. No significant difference in the urinary 8-OHdG levels between exposed workers and control subjects in winter (p=0.923) and summer (p=0.350) was observed. A linear mixed model, adjusted for years of employment, age, ex/non-smoking and BMI, indicated no significant dose exposure-relationships between the urinary 8-OHdG and 15 PAH air concentrations nor between the 8-OHdG and 7 PAH monohydroxy-metabolites analyzed in the same workers. 8-OHdG was also analyzed in the mononuclear cell DNA of 19 exposed and 18 control subjects. The mean value of 8-OHdG/non-modified 2'-deoxyguanosine (8-OHdG/105 dG±SE) were 4.89±0.17 for the exposed and 4.11±0.16 for the control persons, which showed no correlation with the urinary 8-OHdG levels (r=0.01, n=28, P=0.96). The PAH exposure at workplaces was mainly composed of volatile compounds, particularly naphthalene, suggesting low exposure through the respiratory tract and a low effect of PAH in ROS induction.     

Effect of a Single Bout of Exercise and β-Carotene Supplementation on the Urinary Excretion of 8-Hydroxy-deoxyguanosine in Humans

We investigated the effects of acute exhaustive exercise and β-carotene supplementation on urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion in healthy nonsmoking men. Fourteen untrained male (19-22 years old) volunteers participated in a double blind design. The subjects were randomly assigned to either the β-carotene or placebo supplement group. Eight subjects were given 30 mg of β-carotene per day for 1 month, while six subjects were given a placebo for the same period. All subjects performed incremental exercise to exhaustion on a bicycle ergometer both before and after the 1-month β-carotene supplementation period. The blood lactate and pyruvate concentrations significantly increased immediately after exercise in both groups. The baseline plasma p-carotene concentration was significantly 17-fold higher after β-carotene supplementation. The plasma β-carotene decreased immediately after both trials of exercise, suggesting that β-carotene may contribute to the protection of the increasing oxidative stress during exercise. Both plasma hypoxanthine and xanthine increased immediately after exercise before and after supplementation. This thus suggests that both trials of exercise might enhance the oxidative stress. The 24-h urinary excretion of 8-OHdG was unchanged for 3 days after exercise before and after supplementation in both groups. However, the baseline urinary excretion of 8-OHdG before exercise tended to be lower after β-carotene supplementation. These results thus suggest that a single bout of incremental exercise does not induce the oxidative DNA damage, while β-carotene supplementation may attenuate it.     

Correlation of urinary inflammatory and oxidative stress markers in very low birth weight infants with subsequent development of bronchopulmonary dysplasia

Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) ('classic' BPD) and with minimal early lung disease ('atypical' BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1(st), 3(rd) and 7(th) day of life and measured the levels of leukotriene E(4) (LTE(4)) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3(rd) day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7(th) day were the independent risk factor for developing moderate/severe BPD. In 'classic' BPD, the 8-OHdG values on the 3(rd) day were higher than those of 'atypical' BPD. In 'atypical' BPD, the LTE(4) values on the 7(th) day were higher than the values in 'classic' BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in 'atypical' BPD.     

Oxidative stress early in pregnancy and pregnancy outcome

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.