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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.

The amount of 8-hydroxydeoxyguanosine (8-OH-dG) excreted in urine can be used not only as an indicator of DNA repair capacity, but also as a potential marker of oxidative DNA damage. To clarify the oxidation-related factors, in consideration of cancer risk, this study investigated how urinary 8-OH-dG was associated with occupational and lifestyle factors in 372 healthy workers. The creatinine-adjusted urinary 8-OH-dG level was significantly higher in male subjects, smokers and drinkers compared with their counterparts. There were significant positive correlations of the 8-OH-dG level with average number of working hours, involvement in work, average number of cigarettes smoked, average volume of alcohol consumed and serum cortisol level, and there were significant negative correlations of the 8-OH-dG level with body mass index (BMI) and consumption of soybean products, rice and light-colored vegetables. Multiple regression analysis showed that average number of working hours and average number of cigarettes smoked were significant predictors of increased 8-OH-dG levels, whereas being female and BMI were significant predictors of decreased 8-OH-dG levels. Working hours, BMI and smoking were significant predictors of urinary 8-OH-dG in male subjects, whereas age and BMI were significant predictors in female subjects. We suggest that several occupational and lifestyle factors, particularly long working hours and cigarette smoking, are linked to the formation of 8-OH-dG in workers.

The urinary levels of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, of 318 healthy men aged 18 - 58 were measured with high resolution by a newly developed automated high-pressure liquid chromatography (HPLC) system coupled to an electrochemical detector (ECD). The mean 8-OH-dG level (mg / g creatinine) was 4.12 +/- 1.73 (SD). An eleven-fold inter-individual variation was observed. The accuracy of the measurement estimated from the recovery of an added 8-OH-dG standard was 90 - 98%. By univariate analysis, it was found that moderate physical exercise (P = 0.0023) and high body mass index (BMI) (P = 0.0032) reduced the 8-OH-dG level, while physical labor (P = 0.0097), smoking (P = 0.032), and low meat intake (less than once / week) (P = 0.041) increased its level. Based on a multi-regression analysis of the log-transformed values, moderate physical exercise (P = 0.0039), high BMI (P = 0.0099), and age (P = 0.021) showed significant reducing effects on the 8-OH-dG level, while low meat intake (P = 0.010), smoking (P = 0.013), and day-night shift work (P = 0.044) increased its level. These results suggest that many types of life-style factors that either generate or scavenge oxygen radicals may affect the level of oxidative DNA damage of each individual.

The 8‐hydroxydeoxyguanosine (8‐OH‐dG) levels in the peripheral parts of human lung tissues were compared between lung cancer patients (n=70) and non‐cancer patient controls (n=15). An increased level of 8‐OH‐dG was observed in the lung cancer group, in both the adenocarcinoma and non‐adenocarcinoma (mainly squamous cell carcinoma) groups, as compared to the non‐cancer control group. This result suggests that reactive oxygen species are partly involved in the induction of lung carcinomas (both adenocarcinoma and non‐adenocarcinoma).

Arsenicals are epidemiologically significant chemicals in relation to induction of liver cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenicals in mammals, in a rat liver carcinogenesis model. In experiment 1, glutathione-S-transferase placental form (GST-P)-positive foci, putative preneoplastic lesions, were employed as endpoints of a liver medium-term bioassay for carcinogens (Ito test). Starting 2 weeks after initiation with diethylnitrosamine, male F344 rats were treated with 0, 25, 50 or 100 ppm of DMAA in the drinking water for 6 weeks. All animals underwent two-thirds partial hepatectomy at week 3 after initiation. Examination of liver sections after termination at 8 weeks revealed dose-dependent increases in the numbers and areas of GST-P-positive foci in DMAA-treated rats as compared with controls. In experiment 2, ornithine decarboxylase activity, which is a biomarker of cell proliferation, was found to be significantly increased in the livers of rats treated with DMAA. In experiment 3, formation of 8-hydroxydeoxyguanosine, which is a marker of oxygen radical-mediated DNA damage, was significantly increased after administration of DMAA. These results indicate that DMAA has the potential to promote rat liver carcinogenesis, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals.

Ferric nitrilotriacetate (Fe‐NTA) is a renal toxicant and carcinogen in rats and mice. We found that its administration results in formation of 4‐hydroxy‐2‐nonenal (HNE) in the renal proximal tubule cells of rats, and 8‐hydroxydeoxyguanosine (8‐OHdG) adducts in their DNA, suggesting a role for oxidative stress. Since 2‐mercaptoethane sulfonate (MESNA) and N‐acetylcysteine (NAC), administered orally, have been shown to increase the kidney levels of free thiol groups, their influence on the renal toxicity and carcinogenicity induced by Fe‐NTA was examined in the present study. Male Wistar rats were intraperitoneally injected with Fe‐NTA (12 mg Fe/kg), and MESNA (100 mg/kg) or NAC (200 mg/kg) was given orally 1 h before and 1 h after this treatment. The animals were killed for tissue analyses 3 h after the Fe‐NTA exposure. In accord with our previous reports, HNE‐modified protein was detected in the proximal tubules of Fe‐NTA‐treated rats by means of immunohistochemistry. Likewise, levels of 8‐OHdG in the renal nuclear DNA, lipid peroxides as thiobarbituric acid‐reactive substances in the kidneys, and blood urea nitrogen and creatinine in the serum were significantly increased by the Fe‐NTA treatment. All of these changes were completely inhibited by oral administration of MESNA or NAC. These results suggest that both of these compounds can prevent the oxidative stress induced by Fe‐NTA.

Hypertension often occurs in conjunction with insulin resistance. The purpose of this study was to evaluate whether sustained renal hypertension increases the risk of diabetes mellitus in rats, and to define the underlying mechanisms. Two‐kidney, one‐clip hypertensive (2K1C) rats received captopril (50 mg/kg/day), α‐lipoic acid (100 mg/kg/day), or vehicle treatment for 3 months after surgery. Blood pressure was measured by tail cuff plethysmography. Oral glucose tolerance test (OGTT), immunohistochemistry, and western blotting were performed. In addition, insulin secretion from islet cells was measured. OGTT yielded abnormal results, and the number of islet cells and the size of pancreatic β/α cells were decreased in 2K1C rats. Basal insulin levels were also reduced in the plasma. Insulin secretion from pancreatic islet cells in response to high glucose was also attenuated in 2K1C rats compared with sham rats. The levels of oxidative stress markers, including 8‐hydroxydeoxyguanosine and NADPH oxidase‐4, were increased in pancreatic tissue and pancreatic islets in 2K1C rats. The abnormalities observed in 2K1C rats were improved by captopril or α‐lipoic acid treatment. These findings indicate that sustained renal hypertension may lead to pancreatic dysfunction, increasing oxidative stress in pancreatic islets.

Effects of exercise on the formation of 8‐hydroxydeoxyguanosine (8‐OH‐dG), a biomarker of oxidative DNA damage, and other purine metabolites such as hypoxanthine, xanthine and uric acid were examined. Venous blood and urine were collected from swimmers and distance runners before and after the usual training. The amount of 8‐OH‐dG obtained from nuclear DNA of lymphocytes decreased remarkably after intermittent swimming. The amount of nuclear 8‐OH‐dG also declined after distance running, but this difference is statistically not significant. After each exercise, plasma concentrations of hypoxanthine, xanthine and uric acid rose significantly. Urinary excretion of hypoxanthine increased, and xanthine and uric acid decreased after exercise. The 8‐OH‐dG‐to‐creatinine ratio in urine increased slightly after swimming or running. It is supposed that the repair of oxidative DNA damage is augmented by exercise. As far as we know, this is the first report concerning the effect of exercise on oxidative damage in nuclear DNA.

Long-Evans Cinnamon (LEC) rats, a mutant strain originating from Long-Evans rats, spontaneously develop hereditary hepatitis followed by hepatocellular carcinoma. The hepatic disorder in LEC rats is associated with their abnormal copper metabolism; metal-catalyzed reactions often give rise to oxygen radicals, which may be related to the carcinogenesis. By means of high-pressure liquid chromatography with electrochemical detection, cellular DNA damage caused by oxygen radicals can be assessed in terms of the amount of 8-hydroxydeoxyguanosine (oh8dG). We assayed the amount of oh8dG in DNA of liver, kidneys, and brain of LEC and Long-Evans Agouti (LEA) control rats in seven groups (n = 3 to 6) aged from 5 weeks to 24 months. Control rats, a healthy sibling line, were age-matched. The amount of oh8dG was correlated with the severity of the age-related clinical symptoms in LEC rats. The amount was higher in LEC rats than in the controls, especially in the liver at the acute stage of hepatitis. These findings suggest that oxygen radicals may be important in the carcinogenesis that occurs in LEC rats.

Changes in kidney levels of 8-hydroxydeoxyguanosine (8-OH-dG), lipid peroxidation (LPO), glutathione (GSH) and relative organ weight were examined 6, 24, 48, 72 and 96 h after a single i.p. administration of potassium bromate (KBrO3) at a dose of 70 mg/kg to male F344 rats. The 8-OH-dG level was significantly increased 24 h after the treatment at this dose and thereafter gradually decreased. On the other hand, significant elevation in LPO level was observed from 6 h after the treatment with a continuous increase up to a plateau at 48 h and no subsequent drop. GSH level was significantly raised from 6 to 72 h, and relative kidney weight varied in almost the same manner as the 8-OH-dG level. Investigation of the dose-response relation revealed the 8-OH-dG and LPO levels to be significantly increased from a dose of 40 mg/kg KBrO3 in a dose-dependent manner. The results suggest that enhanced formation of 8-OH-dG in kidney DNA due to KBrO3 is closely related to the increase in LPO levels.

Incubation of calf thymus DNA with 3-morpholinosydnonimine (SIN-1), which simultaneously generates nitric oxide (NO) and superoxide (O2−), induced a significant increase of 8-hydroxydeoxyguanosine (8-OH-dG). Peroxynitrite also increased 8-OH-dG in calf thymus DNA. Addition of free hydroxyl radical (•OH) scavengers inhibited the increase of 8-OH-dG by SIN-1 or peroxynitrite. Incubation of 32P-labeled DNA fragment with SIN-1 or peroxynitrite caused DNA cleavage at every nucleotide with a little dominance at guanine residues. The results suggest that NO reacts with O2− to form peroxynitrite and the peroxynitrite induces oxidative DNA damage through an active intermediate of which reactivity is similar to •OH.

8-Hydroxydeoxyguanosine (8-OH-dG) levels were examined in liver and kidney DNA after di(2-ethylhexyl)phthalate (DEHP), di(2-ethylhexyl)adipate (DEHA) and phthalic anhydride administration to male 6-week-old F-344 rats in the diet at concentrations of 1.2, 2.5 and 1.5%, respectively. Significant increases in 8-OH-dG levels were observed only in the liver (target organ of DEHP and DEHA carcinogenesis) DNA after 1 and 2 weeks of treatment with DEHP and DEHA, respectively. The results suggest the involvement of oxidative DNA damage in hepatocarcinogenesis by peroxisome proliferators.