Analysis of oxidative stress expressed by urinary level of biopyrrins and 8-hydroxydeoxyguanosine in patients with chronic schizophrenia.

AIMS: Previous studies have supported the claim that psychological stress induces the production of reactive oxygen species. Several authors have suggested that patients with psychiatric disorders show high levels of oxidative stress markers. We examined different oxidative stress markers in patients with chronic schizophrenia. METHODS: This study included 29 patients with chronic schizophrenia and 30 healthy volunteers. The concentration of urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG), as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. Psychiatric symptoms were assessed by the administration of the Brief Psychiatric Rating Scale (BPRS). RESULTS: The concentration of biopyrrins in patients with chronic schizophrenia was significantly higher when compared with healthy volunteers. The correlation between biopyrrin level and the duration of illness was highly significant. There were no significant differences in the levels of urinary 8-OHdG between the two groups. In schizophrenic patients, the level of urinary biopyrrins showed correlations with BPRS scores, while the level of urinary 8-OHdG did not show correlations with BPRS. CONCLUSIONS: Urinary biopyrrins are increased in patients with chronic schizophrenia while urinary 8-OHdG is not increased. These findings suggest that patients with chronic schizophrenia are under the condition of certain oxidative stresses.

Elevated urinary biopyrrin excretion and oxidative bilirubin metabolism during 24-hour ultramarathon running.

The oxidative metabolite of bilirubin, biopyrrin, is considered a useful candidate marker of oxidative stress in vivo. The present study examines whether urinary biopyrrin excretion is elevated and how general laboratory parameters are changed by long-duration running such as that involved in ultramarathons. Fifteen volunteer runners (12 males and 3 females; aged 44 +/- 9 years; means +/- SD) provided written informed consent to participate in this study. The 24-h experimental run was not a race against time but rather to determine the effects of running around a track for 24 h without sleep and sufficient rest. Blood and urine samples were obtained before (0 h), during (16 h), and immediately after (24 h) running for 24 h. All of the participants completed the run. The mean (+/- SD) distance run was 162.6 +/- 18.3 km. Mean urinary biopyrrin excretion values at 0, 16, and 24 h were 1.23 +/- 0.73, 2.55 +/- 0.95, and 4.00 +/- 1.50 U/g creatinine, respectively. Urinary biopyrrin excretion was positively and significantly correlated with the serum bilirubin concentration (p<0.05) and distance run (p<0.05). These results suggest that urinary biopyrrin excretion could be a useful marker of oxygen stress incurred during a 24-h ultramarathon.

Urinary biopyrrins levels are elevated in relation to severity of heart failure.

OBJECTIVES: We investigated the relationship between the urinary levels of biopyrrins and the severity of heart failure (HF). BACKGROUND: Oxidative stress is evident in heart disease and contributes to the development of ventricular dysfunction in patients with HF. Biopyrrins, oxidative metabolites of bilirubin, have been discovered as potential markers of oxidative stress. METHODS: We measured the levels of urinary biopyrrins and plasma B-type natriuretic peptide (BNP) in 94 patients with HF (59 men; mean age 65 years) and 47 control subjects (30 men; mean age 65 years). Urine and blood samples were taken after admission in all subjects. Further urine samples were obtained from 40 patients after treatment of HF. RESULTS: The urinary biopyrrins/creatinine levels (micromol/g creatinine) were the highest in patients in New York Heart Association (NYHA) class III/IV (n = 26; 17.05 [range 7.85 to 42.91]). The urinary biopyrrins/creatinine levels in patients in NYHA class I (n = 35; 3.46 [range 2.60 to 5.42]) or II (n = 33; 5.39 [range 3.37 to 9.36]) were significantly higher than those in controls (2.38 [range 1.57 to 3.15]). There were significant differences in urinary biopyrrins/creatinine levels among each group. The treatment of HF significantly decreased both urinary biopyrrins/creatinine levels (from 7.43 [range 3.84 to 17.05] to 3.07 [range 2.21 to 5.71]) and NYHA class (from 2.5 +/- 0.1 to 1.7 +/- 0.1). Log biopyrrins/creatinine levels were positively correlated with log BNP levels (r = 0.650, p < 0.001). CONCLUSIONS: These results indicate that urinary biopyrrins levels are increased in patients with HF and are elevated in proportion to its severity.

[Oxidative stress related diseases and biopyrrins].

Reactive oxygen species (ROS) cause damage to the structure and function of tissues. Therefore tissues have systems that eliminate ROS. Bilirubin is one antioxidant that reacts with ROS to produce oxidative metabolites. Biopyrrins are one of the metabolites, the level of which in urine reflects oxidative stress. They are measured by non-competitive inhibition ELISA that employs anti-bilirubin antibody (24G7) and the results are corrected for the urinary concentration of cereatinine. Some reports suggested that psychological stress increased oxidative stress markers. Urinary biopyrrins were also elevated by speech stress, and the subjective stress score recorded by the speakers correlated with the level. The result suggests that bilirubin might eliminate ROS generated by psychological stress. From the beginning of the study of biopyrrins, their urinary level has been known to be increased by surgical stress. Furthermore, it was significantly higher in a major operation patient group than in a minor one, and correlated with operation duration. Sepsis increased the level in surgical patients. Ischemia-reperfusion elevates ROS and, as a result, biopyrrin production. An increase in urinary biopyrrins was observed in a coronary spastic angina group after a spasm provocation test, and the level in myocardial infarction patients with NYHA (New York Heart Association) classification became higher. Correlation between urinary biopyrrins and plasma B-type natriuretic peptide (BNP) was also reported. Research that determines the structures of biopyrrins and their clinical application are in progress.

[Clinical biochemical evaluation of central fatigue with 24-hour continuous exercise].

OBJECTIVE: The present study was conducted to clarify the effects of ultra-marathon (ultra long-term aerobic exercise in which people run long distances) on the brain; examine the issue of central fatigue; verify the serotonin hypothesis of exercise-induced brain fatigue, and ascertain relationships between central fatigue and oxidative stress. METHODS: Subjects consisted of 15 individuals (12 men, 3 women) who ran continuously for 24 h. Mean age was 44 +/- 9 years (range, 31 approximately 64 years). Blood tests were conducted: (1) before starting to run (around 09:00); (2) 16h after starting (02:00 the next day); and (3) just after the finish (around 10:00 the next day) to measure the serum levels of serotonin, melatonin, free tryptophan (f-Tp) and free fatty acid. At the same time, urine samples were collected to measure levels of urinary biopyrrins (BPn). Subjective symptoms were investigated using the Japanese version of the Profile of Mood States (POMS) instrument. RESULTS: (1) Participants ran a mean (+/- SD) distance of 162.6 +/- 18.3 km. (2) There were not marked changes in serum serotonin levels. Serum melatonin levels at 3 time points were 3.4 +/- 0.6 pg/ml, 57.2 +/- 15.2pg/ml and 7.8 +/- 8.9pg/ml, respectively(p < 0.01 before start vs. 16h after start). Serum f-Trp levels at the 3 time points were 5.4 +/- 0.9 nmol/ml, 9.7 +/- 2.1 nmol/ml and 11.5 +/- 4.9 nmol/ml, respectively (p< 0.05 before start vs. just before finish). Free fatty acid levels were 0.42 +/- 0.10 nmol/ml, 1.26 +/- 0.11 nmol/ml and 1.39 +/- 0.23 nmol/ml, respectively (p < 0.01 before start vs. 16 hours after start) (p < 0.05 before start vs. just after finish). (3) Urinary BPn levels increased with time, from 1.2 +/- 0.7 nmol/ml to 2.6 +/- 1.0 nmol/ml to 4.0 +/- 1.5 nmol/ml, respectively (p < 0.01 before the start vs. 16 hours after the start). (4) In terms of POMS scores, fatigue score (Factor F) increased, but vitality score (Factor V) was high at all time points and did not demonstrate any marked changes. Scores for anger and hostility were low (Iceberg profile-type: convex type). Urinary BPn levels were correlated significantly with both serum f-Trp level and Factor F:(y = 8.41x + 2.5, r = 0.708, n = 42) and (y = 2.82x + 5.9, r = 0.568, n = 42), respectively. Urinary BPn thus reflected the degree of subjective fatigue with a high level of sensitivity. CONCLUSIONS: The present results suggest that running continuously for 24h induces brain fatigue and that oxidative stress may be involved.

Effects of lifestyle factors on urinary oxidative stress and serum antioxidant markers in pregnant Japanese women: A cohort study.

Oxidative stress plays a major pathological role in pregnancy-related complications. Although oxidative stress is induced by exogenous toxins in association with a poor lifestyle in normal subjects, there is little information on the factors altering oxidative stress and antioxidant levels during pregnancy. The purpose of this study was to determine the relationship between lifestyle factors and oxidative stress/antioxidant levels during each trimester and 1-month postpartum. This prospective cohort study followed 54 healthy women through pregnancy; first, second, and third trimester and 1-month postpartum. Participants were administered a questionnaire on characteristics and lifestyle factors. Morning blood and urine samples were obtained to measure urinary biopyrrins and serum coenzyme Q10 (CoQ10) levels. The levels of urinary biopyrrins and serum CoQ10 increased significantly throughout pregnancy, with peak values registered during the third trimester. Higher biopyrrin levels were significantly associated with non-consumption of morning meal during the first trimester, smoking during the third trimester and 1-month postpartum, alcohol consumption during the third trimester, high food-based polyunsaturated fatty acid intake during the third trimester, and poor mental health scores during the first and third trimesters. Higher CoQ10 levels were significantly associated with no smoking during pregnancy and at 1-month postpartum, and with a high frequency of exercise during the third trimester and 1-month postpartum. Thus, pregnancy represents a state of oxidative stress, which can be counterbalanced by increased levels of antioxidants, such as CoQ10. We speculate that certain lifestyle choices such as avoiding smoking can reduce oxidative stress and increase antioxidant levels during pregnancy.

Differences in oxidative stress markers based on the aetiology of heart failure: comparison of oxidative stress in patients with and without coronary artery disease.

Various oxidative stress markers have been measured to evaluate the status of heart failure (HF). However, the relationships between these markers and the aetiology of HF have not been fully investigated. This study compared 8-hydroxy-2'-deoxyguanosine (8-OHdG) and biopyrrins levels in patients with ischemic and non-ischemic HF. Study subjects were divided into a coronary artery disease (CAD) group (n=70), a non-CAD group (n=61) and a control group (n=33). In the CAD group, 8-OHdG and biopyrrins levels increased with the severity of the New York Heart Association (NYHA) functional class and log BNP levels correlated with 8-OHdG and biopyrrins levels. However, non-CAD patients with NYHA class III/IV had significantly lower 8-OHdG levels than CAD patients with NYHA class III/IV and the levels did not correlate with log BNP levels. In the CAD group, 8-OHdG levels reflected the severity of atherosclerosis. These results indicate that the properties of oxidative stress markers should be carefully taken into consideration for the assessment of HF status.

Diurnal variation of biopyrrin excretion in random urine specimens is not corrected by creatinine.

Circulating bilirubin is thought to function as a physiological antioxidant. One of the decomposition products of this process is the biopyrrins, which include two regioisomers: biotripyrrin-a (1,14,15,17-tetrahydro-2,7,13-trimethyl-1,14-deoxy-3-vinyl-16H-tripyrrin-8,12-dipropionic acid) and biotripyrrin-b (1,14,15,17-tetrahydro-3,7,13-trimethyl-1,14-deoxy-3-vinyl-16H-tripyrrin-8,12-dipropionic acid). We measured biopyrrins in random urine specimens and investigated whether the biopyrrin values obtained were valid when expressed as a ratio of the creatinine (Cr) concentrations. All of the random urine specimens collected over 48 hr were from presumably healthy adults. We measured the biopyrrins by means of an enzyme-linked immunosorbent assay (ELISA) using an anti-bilirubin monoclonal antibody. When the values were expressed in terms of the ratio to Cr, the within-day coefficient of variation (%CV) of the excretion of biopyrrins was reduced to 27%+/-10% (P<0.05) from 59%+/-27%. However, assay values on random or spot urine specimens were unreliable because of the large %CV. The biopyrrin concentrations only in the first-morning-urine specimens in terms of both absolute amounts and ratios to Cr significantly reflected those in a 24-hr urine specimen (P<0.001). Concentrations in a random urine specimen voided at the second collection or later did not correlate with the concentration in a 24-hr urine specimen (P>0.05), even if their values were corrected by Cr. The amounts of biopyrrins excreted in 24-hr urine specimens were significantly correlated with the 24-hr cortisol excretion (P<0.001) but not to uropepsin (P>0.05).

Psychological stress increases bilirubin metabolites in human urine.

Some authors have suggested that psychological stress induces the production of reactive oxygen species (ROS). Some studies have supported that bilirubin exerts anti-oxidative effects in vivo. However, it is not known whether ROS induced by psychological stress provoke bilirubin oxidation in vivo. We investigated if the concentration of bilirubin oxidative metabolite (BOM), a bilirubin oxidative metabolite, increased in urine from subjects exposed to psychological stress. Sixty healthy male volunteers working in a pharmaceutical company were divided into a Group I which did not attend a conference, a Group II which attended a conference but did not deliver a speech, and a Group III which attended a conference and delivered speeches in the presence of the company executives. Subjective stress was scored (self-rating score) after subjects in Group III delivered their speeches at the conference. Urine was collected on the next day. The BOM concentrations, as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. The concentration of BOM in Group III was significantly higher compared to that in Groups I and II (p<0.01 and p<0.05, respectively). Furthermore, in Group III, the concentration of BOM correlated with the self-rating stress score (r=0.53, p<0.01). These findings suggest that emotional stimuli are associated with an increase in the oxidative metabolites of bilirubin in human urine, and that BOMs could be useful markers of psychological stress.

Effort-reward imbalance and physical health among Japanese workers in a recently downsized corporation.

OBJECTIVES: The present study investigated the effort-reward imbalance (ERI) model-related biological markers of disease risks in Japanese workers of a recently downsized manufacturing corporation. METHODS: A total of 441 workers was examined to find whether situational effort-reward imbalance or personal overcommitment was associated with hematological and biochemical measurements, serum cortisol, and urine biopyrrins as oxidative metabolites of antioxidant bilirubin. RESULTS: The effort-reward imbalance was positively associated with the values of red blood cells, hemoglobin, hematocrit, triglycerides and glutamic pyruvic transaminase (GPT), and negatively correlated with the high-density lipoprotein cholesterol level. Overcommitment was positively related to the values of hematocrit and glucose levels, but negatively associated with the total protein level. The relationships between effort-reward imbalance and GPT level, and that between overcommitment and glucose level, persisted when potential confounders were adjusted for. The ERI model was not significantly related to either cortisol or biopyrrins levels. CONCLUSIONS: The ERI model seems to have an impact on the physical health of the downsized Japanese workers, although the results are mixed and are different from those in workers of Western countries.

Associations between oxidative stress levels and total duration of engagement in jobs with exposure to fly ash among workers at municipal solid waste incinerators.

The fly ash from municipal solid waste incinerators (MSWIs) is known to contain heavy metals, polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polyaromatic hydrocarbons (PAHs), and other organic materials. Heavy metals, PCDDs, PCDFs and PAHs reportedly cause oxidative stress in vitro and in vivo. In this study, we have measured the blood and urinary levels of several oxidative stress markers in MSWI workers and discuss herein whether the duration of engagement in jobs with exposure to MSWI fly ash is associated with these levels. The subjects were 81 male workers (mean age 42.7 years) from four MSWIs in the same city. Job history was determined from each subject and jobs were categorized according to the possibility of exposure to fly ash. The subjects were classified into four groups: long duration of engagement in jobs with exposure to fly ash, short duration of engagement in jobs with exposure to fly ash, engagement in jobs with limited exposure to fly ash and control. Blood and urine specimens were obtained from the subjects in the morning before breakfast. The levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in the urine and leukocytes were measured as markers of oxidative DNA damage. Blood malondialdehyde and lipid peroxide levels and the level of total urinary biopyrrins were also measured as markers of systemic oxidative stress. The mean levels of all markers were compared among the four groups. There was a significant trend showing that the level of urinary 8-OH-dG rose with increased duration of engagement in jobs with exposure to MSWI fly ash (P<0.05). Considering this result, we speculate that certain chemicals in fly ash might have induced oxidative stress in the study subjects.