Excretion Of 8-hydroxydeoxyguanosine Research Articles

Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men.

Molecular hydrogen has been suggested to have a cytoprotective effect on the whole body and to enhance exercise performances. However, the effect of hydrogen-rich gas mixture (HG) inhalation on physiological responses has been poorly investigated. We examined the impact of acute HG inhalation on subsequent oxidative stress, muscle damage, and exercise performances during the recovery period after a strenuous exercise. This is a two-trial, double-blind, crossover, repeated measures study. Eight physically active male volunteers inhaled HG (estimated fraction of inspired oxygen and hydrogen were 21.57 and 4.08% at most, respectively) or normal gas (placebo, ambient air 400 m above sea level) during a 60-minute recovery phase after oxidative stress-inducing exercise) completion comprising 30-minute treadmill running at an intensity corresponding to 75% of maximal oxygen uptake and squat jumps (5 sets × 10 repetitions). Before oxidative stress-inducing exercise and 10 minutes after the post-exercise gas inhalation, blood and urine samples were obtained and exercise performances (jumping ability; pedaling power output; muscle strength) were evaluated. Post-exercise HG inhalation attenuated the increase in urinary 8-hydroxydeoxyguanosine excretion rate (P < 0.05), a DNA oxidation marker, and the reduction in the countermovement jump height (P < 0.05), compared with Placebo inhalation. Other exercise performances and blood oxidative stress and muscle damage markers did not differ between HG and Placebo inhalation. Moreover, the increase in urinary 8-hydroxydeoxyguanosine excretion rate was significantly associated with countermovement jump performance reduction (r = –0.78, P < 0.01). These findings suggested that HG inhalation during post-exercise recovery period might improve exercise performance via reducing systemic oxidative damage. The study was approved by the Human Research Ethics Committee of the University of Yamanashi (approval No. H29-006) on June 28, 2017.

Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage.

Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. This cross-sectional study included 6517 individuals aged 45 to 74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector. Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one-category increase of stress; ptrend = .025), even after adjusting for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG. In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.

Oxidative DNA damage during night shift work

ObjectivesWe previously reported that compared with night sleep, day sleep among shift workers was associated with reduced urinary excretion of 8-hydroxydeoxyguanosine (8-OH-dG), potentially reflecting a reduced ability to repair 8-OH-dG...

The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus.

Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes. At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed. To evaluate the effect of OCT on the renin-angiotensin system, we performed a further study using aliskiren (ALS). At 20 weeks, the diabetic rats were divided into two groups: the ALS-treated group (ALS) and the ALS plus OCT-treated group (ALS + OCT), and we evaluated the renin-angiotensin system (RAS) and cardiac lesions at 30 weeks. At 30 weeks, despite comparable blood pressure and renal function, heart volume, intracardiac oxidative stress by immunohistological analysis, cardiac and perivascular fibrosis and urinary excretion of 8-hydroxydeoxyguanosine and serum N-terminal pro-brain natriuretic peptide levels were significantly decreased in the OCT group compared to the DM group. mRNA expressions of dihydronicotinamide adenine dinucleotide phosphate (NADPH) p47 subunit and cardiac injury-related markers in the heart were also significantly decreased in the OCT group compared to the DM group. The cardioprotective effect of OCT was preserved even in the context of RAS inhibition. Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition.

Consumption of 5-hydroxymethylfurfural-rich dried fruits is associated with reduction in urinary excretion of 8-hydroxy-2′-deoxyguanosine: a randomized clinical trial

5-Hydroxymethylfurfural is widely presented in foods and produced through the degradation of hexoses and the Maillard reaction. This study aimed to investigate any association between 5-HMF content of consumed dried fruits and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG). The study consisted of 75 healthy volunteers. After an overnight fasting, two urine samples were collected before and 5 h after consumption of date, apricot, currant, plum and fruit bread, 100 g each. Twenty-five samples from frequently consumed types of dried fruits were analyzed for 5-HMF with HPLC. Urinary 5-hydroxymethyl-2-furoic acid (HMFA) and 8-OHdG were determined using HPLC and ELISA, respectively. The amount of 5-HMF in the tested samples varied from 314.8 ± 166.1 to 2496.3 ± 2301.2 mg/kg. The lowest and highest levels of 8-OHdG were 10.1 ± 1.5 µg/g creatinine for plum and 24.7 ± 6.6 µg/g creatinine for date. At the two time points, mean HMFA levels varied from 630.6 ± 114.5 to 2116.8 ± 600.3 and 286.7 ± 24.8 to 582.0 ± 119.2 (µg/g creatinine), respectively. There was a significant difference in HMFA amounts of the samples before and after consumption of apricot and plum (P 0.66, P < 0.01). It is concluded that consumption of 5-HMF-rich dried fruits is associated with a significant reduction in urinary excretion of 8-OHdG.

Anti-oxidative effect of the β-blocker carvedilol on diabetic nephropathy in non-obese type 2 diabetic rats.

Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The β-blocker carvedilol has been proven to have an anti-oxidant property. The aim of the present study was to elucidate the effects of carvedilol on diabetic nephropathy. At 20weeks of age, male Spontaneously Diabetic Torii (SDT) rats were divided into three groups based on treatment: (i) an INS group (administered insulin); (ii) a CAR group (administered 10mg/kg per day, p.o., carvedilol); and (iii) a diabetic (DM) group (administered vehicle). Rats were treated for a period of 10weeks and were killed at 30weeks of age. Urinary albumin excretion, renal histomorphology, and oxidative stress were evaluated. Urinary albumin excretion was significantly lower in the CAR than DM group (42.82±3.94 vs 76.62±13.74mg/day respectively; P<0.05). The mesangial index was lower in the CAR group than in the DM group. Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), the number of 8-OHdG-positive cells in glomeruli, and the mRNA expression of NADPH oxidase p22phox and p47phox were also lower in the CAR than DM group. However, haemoglobin A1c (HbA1c) and blood pressure levels were comparable between the two groups. The results suggest that carvedilol could prevent the progression of diabetic nephropathy by suppressing oxidative stress.

Increased oxidative DNA damage seen in renal biopsies adjacent stones in patients with nephrolithiasis.

Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, is significantly higher in nephrolithiasis patients than in healthy individuals, indicating that these patients have higher degree of oxidative stress. In the present study, we investigated 8-OHdG expression in renal biopsies of patients with nephrolithiasis and in renal tubular cells (HK-2 cells) exposed to calcium oxalate monohydrate (COM). We performed immunohistochemical staining for 8-OHdG in renal biopsies adjacent stones obtained from 28 patients with nephrolithiasis. Controls were noncancerous renal tissues from nephrectomies of patients with renal cancer. 8-OHdG was overexpressed in the nucleus of renal tubular cells in patients with nephrolithiasis compared with controls. Only one nephrolithiasis biopsy was negative for 8-OHdG, whereas in 19 cases 8-OHdG was highly expressed. The level of expression of 8-OHdG among patients with calcium oxalate (mostly mixed with calcium phosphate) and uric acid stones was not significantly different. Increased leukocyte infiltration was observed in renal tissues from patients with nephrolithiasis. Exposure of HK-2 cells to COM caused increased intracellular reactive oxygen species and nuclear expression of 8-OHdG. To our knowledge, this is the first report of increased 8-OHdG expression in renal tubular cells of patients with nephrolithiasis. In vitro, COM crystals were capable of inducing oxidative damage of DNA in the proximal renal tubular cells.

Oxidative stress: A cause and therapeutic target of diabetic complications.

Oxidative stress is defined as excessive production of reactive oxygen species (ROS) in the presence of diminished anti-oxidant substances. Increased oxidative stress could be one of the common pathogenic factors of diabetic complications. However, the mechanisms by which hyperglycemia increases oxidative stress are not fully understood. In this review, we focus on the impact of mitochondrial derived ROS (mtROS) on diabetic complications and suggest potential therapeutic approaches to suppress mtROS. It has been shown that hyperglycemia increases ROS production from mitochondrial electron transport chain and normalizing mitochondrial ROS ameliorates major pathways of hyperglycemic damage, such as activation of polyol pathway, activation of PKC and accumulation of advanced glycation end-products (AGE). Additionally, in subjects with type 2 diabetes, we found a positive correlation between HbA1c and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), which reflects mitochondrial oxidative damage, and further reported that 8-OHdG was elevated in subjects with diabetic micro- and macro- vascular complications. We recently created vascular endothelial cell-specific manganese superoxide dismutase (MnSOD) transgenic mice, and clarified that overexpression of MnSOD in endothelium could prevent diabetic retinopathy in vivo. Furthermore, we found that metformin and pioglitazone, both of which have the ability to reduce diabetic vascular complications, could ameliorate hyperglycemia-induced mtROS production by the induction of PPARγ coactivator-1α (PGC-1α) and MnSOD and/or activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). We also found that metformin and pioglitazone promote mitochondrial biogenesis through the same AMPK-PGC-1α pathway. Taking these results, mtROS could be the key initiator of and a therapeutic target for diabetic vascular complications. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00013.x, 2010).

Lipid peroxidation in early type 1 diabetes mellitus is unassociated with oxidative damage to DNA

Oxidative stress damages DNA in experimental diabetes, and in vitro studies have suggested that it is linked to lipid peroxidation. The objective of the study was to determine whether lipid peroxidation, as assessed with malondialdehyde excretion in recent-onset type 1 diabetes mellitus, is associated with oxidative damage to DNA, as assessed from 8-hydroxydeoxyguanosine excretion. A 3-year longitudinal study of recent-onset type 1 diabetes mellitus was performed. Age- and sex-matched control subjects were studied once. Patients were studied as inpatients at West Virginia University Hospitals. Thirty-seven patients with recent-onset (2-22 months) type 1 diabetes mellitus (male ,10; female, 27) were enrolled in a longitudinal study of oxidative stress. The mean age of the patients was 20 years. None of the patients had hyperlipidemia or were treated with lipid-lowering drugs. Only 1 patient had hypertension and was being treated with β-adrenergic blocking therapy. Thirty-six patients completed the study; one withdrew after the second evaluation. Lipid peroxidation was assessed by measuring malondialdehyde excretion. Oxidative damage to DNA was assessed from 8-hydroxydeoxyguanosine excretion. Malondialdehyde excretion was increased in the diabetic patients at the first evaluation (2.43 ± 0.31 μmol/g creatinine), second evaluation (2.34 ± 0.24), and third evaluation (1.93 ± 0.15) compared with control subjects (1.51 ± 0.11) ( P < .005). 8-Hydroxydeoxyguanosine excretion, however, was not increased in the diabetic patients. There was no correlation between malondialdehyde and 8-hydroxydeoxyguanosine excretion. We confirmed the presence of oxidative stress in early diabetes as assessed from malondialdehyde excretion. We were unable, however, to confirm oxidative damage to DNA in this cohort of patients; and there was no evidence of a correlation between lipid peroxidation and DNA damage.

Effects of chronic chromium picolinate treatment on glycemic control and kidney function of db/db mice

Previous studies suggest a clastogenic effect of chromium picolinate (Cr(Pic)3). We tested the hypothesis that Cr(Pic)3 improves glycemic status accompanied by decreased renal accumulation and excretion of 8‐hydroxy deoxyguanosine (8‐OHdG). Male db/db mice were fed diets lacking or containing 5 or 100 mg/kg chromium (as Cr(Pic)3) from 6‐24 weeks of age; lean nondiabetic db/m mice served as controls. The untreated db/db mice displayed marked elevation in hemoglobin A1c than db/m controls. The db/db mice fed the 100 (but not 5) mg/kg diet displayed lower hemoglobin A1c (p&lt;0.05). As expected, total proteinuria and albumin excretion were significantly greater in db/db than db/m mice; Cr(Pic)3 reduced total protein and albumin excretions in db/db mice. Urinary excretion of 8‐OHdG was also significantly higher in the untreated db/db than db/m mice and dietary Cr(pic)3 treatment reduced urinary 8‐OHdG excretion. Renal tubular cells of the db/db kidney showed moderate‐intense immunoreactivity for 8‐OHdG in the form of cytoplasmic microgranules. Interestingly, renal tissue of the Cr(Pic)3‐treated db/db mice showed a decrease in the intensity of staining for 8‐OHdG than those of untreated db/db mice. Taken together, the data suggest that while Cr(Pic)3 does not increase the propensity for oxidative DNA damage, it exerts dose‐dependent effects on glycemic control and kidney function in db/db mice. Supported by NIH.

Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress

Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease (CVD). Increased oxidative stress plays a role in the pathogenesis of CVD in CKD patients. The oral charcoal adsorbent AST-120 attenuates the progression of CKD possibly by removing uraemic toxins such as indoxyl sulfate (IS), and reduces oxidative stress. We investigated the relationship between oxidative stress and cardiac damage in CKD and its prevention by AST-120. Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed. At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 +/- 0.28 mL/min versus 1.60 +/- 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 +/- 0.46 mL/min versus 0.75 +/- 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores. Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.

Effects of chromium picolinate on glycemic control and kidney of the obese Zucker rat

BackgroundChromium picolinate (Cr(pic)3) is advocated as adjuvant therapy for impaired glycemic control, despite concerns for DNA damage. Potential toxicity of Cr(pic)3 should be greater for the kidney that accumulates chromium. Therefore, we tested the hypothesis that Cr(pic)3 treatment of obese Zucker rats (OZR) exacerbates renal abnormalities associated with dysglycemia.MethodsMale OZR were treated with diets lacking or containing 5 and 10 mg/kg of chromium, as Cr(pic)3, for 20 weeks; lean Zucker rats (LZR) served as controls. Glycemic and renal effects of Cr(pic)3 were determined in the context of indices of oxidative stress and inflammation.ResultsThe OZR displayed increased fasting plasma glucose and insulin in association with enlarged pancreatic islets exhibiting collagen and periodic acid Schiff-positive deposits compared to LZR; Cr(pic)3 treatment did not affect these parameters. The OZR, irrespective of Cr(pic)3, excreted more albumin than LZR. Also, other indices of renal function or histopathology were not affected by Cr(pic)3 treatment. Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), an index of oxidative DNA damage, was greater in the OZR than LZR; dietary Cr(pic)3 treatment attenuated 8-OHdG excretion. However, immunostaining of kidney for 8-OHdG revealed similar staining pattern and intensity, despite significant renal accumulation of chromium in Cr(pic)3-treated groups. Finally, increased renal nitrotyrosine and cyclooxygenase-2 levels and urinary excretion of monocyte chemoattractant protein-1 of OZR were partially reversed by Cr(pic)3 treatment.ConclusionDietary Cr(pic)3 treatment of OZR does not beneficially influence glycemic status or increase the risk for oxidative DNA damage; rather, the treatment attenuates indices of oxidative stress and inflammation.

Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia: A novel role of oxidative stress and therapeutic implications

Diabetes mellitus is associated with increased risk of osteopenia and bone fracture. However, the mechanisms accounting for diabetic bone disorder are unclear. We have previously reported that streptozotocin-induced diabetic mice develop low turnover osteopenia associated with increased oxidative stress in the diabetic condition. To determine the role of oxidative stress in the development of diabetic osteopenia, we presently investigated the effect of overexpression of thioredoxin-1 (TRX), a major intracellular antioxidant, on the development of diabetic osteopenia, using TRX transgenic mice (TRX-Tg).TRX-Tg are C57BL/6 mice that carry the human TRX transgene under the control of β-actin promoter. Eight-week-old male TRX-Tg mice and wild type (WT) littermates were intraperitoneally injected with either streptozotocin or vehicle. Mice were grouped as 1) non-diabetic WT, 2) non-diabetic TRX-Tg, 3) diabetic WT, and 4) diabetic TRX-Tg. After 12 weeks of streptozotocin treatment, oxidative stress on the whole body and bone was evaluated, and the physical properties of the femora, and histomorphometry parameters of the tibiae were assessed.TRX overexpression did not affect either body weight or hemoglobin A1c levels. There were no significant differences in renal function and in serum levels of calcium, phosphate, and intact parathyroid hormone among the four groups. On the other hand, urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly elevated in diabetic WT and attenuated in diabetic TRX-Tg. Immunohistochemical staining for 8-OHdG revealed marked intensity in the bone tissue of diabetic WT compared with non-diabetic WT, while staining was attenuated in diabetic TRX-Tg. TRX overexpression partially restored reduced bone mineral density and prevented the suppression of bone formation observed in diabetic WT. Increased oxidative stress in diabetic condition contributes to the development of diabetic osteopenia. Suppression of increased oxidative stress by TRX induction could be a potential therapeutic approach for diabetic osteopenia.

Evaluation of oxidative stress in a group of adolescents exposed to a high level of aflatoxin B1 a multi-center and multi-biomarker study

The association between aflatoxin B1 (AFB1) exposure and oxidative stress was extensively examined in 84 adolescents from an area at high risk for hepatocellular carcinoma in China. Plasma level of aflatoxin B1-albumin adducts (AAAs) was associated with AFB1 excretion in urine (r = 0.394, P < 0.001). Urinary AFB1 was also associated with both the urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG) (r > or = 0.479, P < 0.001) and 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.308, P < or = 0.005). Similarly, AAA was significantly associated with both the urinary excretion of 8-OHdG (r > or = 0.259, P < or = 0.018) and the 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.313, P < or = 0.004). In addition, urinary 8-OHdG was correlated with both the level of DNA 8-OHdG (r > or = 0.24, P < or = 0.05) and the expression of hOGG1 in peripheral leukocytes (r > or = 0.429, P < 0.001). Protein carbonyl content (PCC) level was significantly associated with not only the level of DNA 8-OHdG (r > or = 0.366, P < 0.001) and the urinary 8-OHdG (r > or = 0.258, P < or = 0.018) but also the expression of hOGG1 in peripheral leukocytes (r = 0.485, P < 0.001). A significant but weak association was found between high-performance liquid chromatograph-electrochemical detection (HPLC-ECD) and enzyme-linked immunosorbent assay (ELISA) for urinary 8-OHdG (r = 0.334, P = 0.002) and between HPLC-ECD and flow cytometry assays for 8-OHdG in leucocytes (r = 0.395, P < 0.001). Significant associations were observed between AAA and PCC and liver function indices (alanine aminotransferase and aspartate aminotransferase). These findings suggest significant contribution from AFB1 exposure to oxidative stress and subsequent repair among adolescents that may impose substantial risk for hepatocarcinogenesis in adulthood in this region.

Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: A possible role of oxidative stress

Diabetic osteopenia causes an increase in bone fracture and a delay in healing of fractures, and affects the quality of life. However, the mechanisms responsible for the disease have not been clearly identified. Oxidative stress may be a potential candidate for the pathogenesis, since it is increased under diabetic conditions and is known to induce cellular dysfunction in a wide variety of cell types. Although in vitro studies have shown that oxidative stress inhibits osteoblastic differentiation and induces osteoblast insults and apoptosis, the relationship between diabetic osteopenia and oxidative stress remains unclear. To explore these issues, analysis of a mouse model that represents the diabetic osteopenia as seen in patients with diabetes is necessary. However, there are few reports of such a model. Therefore, we focused on the streptozotocin (STZ)-induced diabetic mouse, one of the most common animal models of type 1 diabetes. Eight-week-old male C57BL/6 mice were randomly assigned to the following three groups: 1) control group, 2) diabetic group, and 3) insulin-treated diabetic group. After 12 weeks of STZ treatment, the physical properties of the femora, and the static and dynamic parameters of bone histomorphometry of the tibiae from STZ-induced diabetic mice (STZ-mice) were assessed, and oxidative stress in the whole body and bone of the mice was evaluated. Renal function was comparable in all three groups at the end of the experimental period. In addition, no significant difference in serum PTH, Ca, and P was found among the three groups. In contrast, radiological analysis demonstrated a significant decrease in trabecular bone volume, and histomorphometric analyses confirmed that parameters for both bone formation (OV/BV, OS/BS, and BFR/BS) and bone resorption (ES/BS and Oc.S/BS) were also significantly lower in STZ-mice. In addition, urinary excretion of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, was elevated in STZ-mice. Further immunohistological studies showed intensified immunostaining of an oxidative stress marker in bone tissue including the osteoblasts of diabetic mice. Here, we demonstrated that STZ-mice exhibit low-turnover osteopenia associated with increased oxidative stress.

Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

Modulation by lycopene of aflatoxin B(1) (AFB(1))-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB(1) (250 microg/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB(1) (250 mug/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB(1) and greatly modulated AFB(1) metabolism and metabolic activation. Urinary excretion of AFB(1) phase 1 metabolites, AFM(1), AFQ(1), and AFP(1), was significantly decreased in lycopene-treated animals. Formation of serum AFB(1)-albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p<0.05) to 67.7% on day 15 (p<0.001). Lycopene intervention also significantly reduced formation of AFB(1)-DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p<0.05). Levels of AFB(1)-N(7)-guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB(1)-mecapturic acid, was significantly increased in lycopene-intervened animals. AFB(1)-induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene.

Increased urinary excretion of 8-hydroxydeoxyguanosine in engine room personnel exposed to polycyclic aromatic hydrocarbons

Background: Previous investigations indicate that engine room personnel on ships are exposed to polycyclic aromatic hydrocarbons (PAH) from oil and oil products, with dermal uptake as the major route of...

Translocation of Glomerular p47phox and p67phox by Protein Kinase C-β Activation Is Required for Oxidative Stress in Diabetic Nephropathy

Oxidative stress is implicated to play an important role in the development of diabetic vascular complications, including diabetic nephropathy. It is unclear whether oxidative stress is primarily enhanced in the diabetic glomeruli or whether it is merely a consequence of diabetes-induced glomerular injury. To address this issue, we examined diabetic glomeruli to determine whether oxidative stress is enhanced, as well as examined the role of protein kinase C (PKC)-beta activation in modulating NADPH oxidase activity. Urinary 8-hydroxydeoxyguanosine excretion and its intense immune-reactive staining in the glomeruli were markedly higher in diabetic than in control rats, and these alterations were ameliorated by a treatment with a selective PKC-beta inhibitor, ruboxistaurin (RBX; LY333531) mesylate, without affecting glycemia. NADPH oxidase activity, which was significantly enhanced in diabetic glomeruli and the source of reactive oxygen species (ROS) generation, was also improved by RBX treatment by preventing the membranous translocation of p47phox and p67phox from cytoplasmic fraction without affecting their protein levels. Adenoviral-mediated PKC-beta(2) overexpression enhanced ROS generation by modulating the membranous translocation of p47phox and p67phox in cultured mesangial cells. We now demonstrate that oxidative stress is primarily enhanced in the diabetic glomeruli due to a PKC-beta-dependent activation of NADPH oxidase resulting in ROS generation.

Urinary 8‐hydroxydeoxyguanosine excretion in children before and after therapy for eradication of Helicobacter pylori infection

Aim: A number of reports have implicated oxygen free radicals in the pathogenesis of Helicobacter pylori (H. pylori)‐associated disease. 8‐hydroxydeoxyguanosine (8‐OHdG) has recently been accepted as a sensitive marker for reflecting the oxidative DNA damage. However, there have been no previous studies comparing the changes in urinary 8‐OHdG excretions before and after therapy for eradication of H. pylori infection, or to examine 8‐OHdG excretions in children with H. pylori infection. The aim of this study was therefore to examine the DNA damage in gastric mucosal cells in children with H. pylori infection. Methods: Urinary 8‐OHdG excretions were measured before and after therapy for eradication of H. pylori infection in 15 children diagnosed with the H. pylori infection and 13 parents who were also suffering from the same infection. Results: In both the children and their parents, no significant differences were found in urinary 8‐OHdG excretions either before or after the eradication therapy. Furthermore, there was no significant difference in urinary 8‐OHdG excretions between 8 children with peptic ulcers and 7 children without ulcers, either before or after the therapy. Conclusion: These results suggest that measurement of urinary 8‐OHdG levels is not useful for evaluation of the DNA damage in H. pylori‐infected gastric mucosa in children.

Urinary 8-hydroxydeoxyguanosine excretion in children before and after therapy for eradication of Helicobacter pylori infection.

A number of reports have implicated oxygen free radicals in the pathogenesis of Helicobacter pylori (H. pylori)-associated disease. 8-hydroxydeoxyguanosine (8-OHdG) has recently been accepted as a sensitive marker for reflecting the oxidative DNA damage. However, there have been no previous studies comparing the changes in urinary 8-OHdG excretions before and after therapy for eradication of H. pylori infection, or to examine 8-OHdG excretions in children with H. pylori infection. The aim of this study was therefore to examine the DNA damage in gastric mucosal cells in children with H. pylori infection. Urinary 8-OHdG excretions were measured before and after therapy for eradication of H. pylori infection in 15 children diagnosed with the H. pylori infection and 13 parents who were also suffering from the same infection. In both the children and their parents, no significant differences were found in urinary 8-OHdG excretions either before or after the eradication therapy. Furthermore, there was no significant difference in urinary 8-OHdG excretions between 8 children with peptic ulcers and 7 children without ulcers, either before or after the therapy. These results suggest that measurement of urinary 8-OHdG levels is not useful for evaluation of the DNA damage in H. pylori-infected gastric mucosa in children.