8-hydroxy-2--deoxyguanosine and Weight-Gain

The aim of this study was to investigate if purple carrot extract is able to protect against the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis, genotoxicity and oxidative status were investigated in this setting. A total of twenty Wistar rats weighing 250g on the average, and 8 weeks age were distributed into four groups (n=5), as follows: Control group (non-treated group, CTRL); Cadmium group (Cd) and Purple carrot extract groups at 400mg/L or 800mg/L. Histopathological analysis revealed that liver from animals treated with purple carrot extract improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as depicted by comet and micronucleus assays in animals treated with purple carrot extract. SOD-CuZn and cytocrome C gene expression increased in groups treated with purple carrot extract. Purple carrot extract also reduced the 8OHdG levels in liver cells when compared to cadmium group. Taken together, our results demonstrate that purple carrot extract is able to protect against cadmium intoxication by means of reducing tissue regeneration, genotoxicity and oxidative stress in multiple organs of Wistar rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Bone Marrow Cells; Cadmium Poisoning; Comet Assay; Cytochromes c; Daucus carota; Deoxyguanosine; DNA Damage; Gene Expression Regulation; Immunohistochemistry; Liver; Micronucleus Tests; Mutagens; Organ Specificity; Oxidative Stress; Plant Extracts; Rats, Wistar; Real-Time Polymerase Chain Reaction; Spectrometry, Mass, Electrospray Ionization; Weight Gain

Indole-3-carbinol (I3C) has a liver tumor promoting activity in rats, and is also known as a cytochrome p450 1A (CYP1A) inducer. The generation of reactive oxygen species (ROS) resulting from CYP1A induction due to I3C, is probably involved in the tumor promotion. To clarify whether ROS generation contributes to I3C's induction of hepatocellular altered foci, partially hepatectomized rats were fed a diet containing 0.5% of I3C for 8 weeks with or without 0.3% N-acetyl-L-cysteine (NAC), an antioxidant, in their drinking water after N-diethylnitrosamine (DEN) initiation. Immunohistochemical analysis showed that the glutathione-S-transferase placental form (GST-P) positive foci promoted by I3C were suppressed by the administration of NAC. The mRNAs of members of the phase II nuclear factor, erythroid derived 2, like 2 (Nrf2) gene batteries, whose promoter region is called as antioxidant response element (ARE), were down-regulated in the DEN-I3C-NAC group compared to the DEN-I3C group, but Cyp1a1 was not suppressed in the DEN-I3C-NAC group compared to the DEN-I3C group. There was no marked difference in production of microsomal ROS and genomic 8-hydroxy-2'-deoxygunosine (8-OHdG) as an oxidative DNA marker between the DEN-I3C-NAC and DEN-I3C groups, while mapkapk3 and Myc were decreased by the NAC treatment. These results indicate that oxidative stress plays an important role for I3C's tumor promotion, and NAC suppresses induction of hepatocellular altered foci with suppressed cytoplasmic oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcysteine; Alkylating Agents; Animals; Antioxidants; Carcinogens; Deoxyguanosine; Diethylnitrosamine; DNA Damage; Gene Expression Profiling; Hepatectomy; Indoles; Liver Neoplasms, Experimental; Male; Microsomes, Liver; Oligonucleotide Array Sequence Analysis; Organ Size; Oxidative Stress; Rats; Rats, Inbred F344; Reactive Oxygen Species; Weight Gain

Short-term inhalation experiments were performed using Fischer 344 rats exposed to emission from the urea selective catalytic reduction (SCR) diesel engine system to identify health effects and compare them to those of the conventional diesel engine system. Rats were exposed to high-, middle-, or low-concentration emission (dilution ratio 1:29, 1:290, or 1:580) or clean air (control) for 1, 3, or 7 days (6 h/day), under driving conditions at a speed of 1320 rpm and a torque of 840 Nm. For the high-concentration group, the major components of the urea SCR emission were 0.04 mg/m(3) particulate matter (PM) and 0.78 ppm nitrogen dioxide (NO(2)); those of the conventional emission were 0.95 mg/m(3) PM and 0.31 ppm NO(2). The authors evaluated the respiratory effects of each emission on rats. Lymphocytes for 3-day exposure of both emissions significantly increased in bronchoalveolar lavage fluid, but there were slight differences. With an increase in potential antioxidant (PAO), 8-hydroxy-2'-deoxyguanosine for the urea SCR emission was significantly decreased, but that of the conventional emission was highest among all groups and did not show a response to PAO. In lungs, heme oxygenase (HO)-1 and tumor necrosis factor (TNF)-alpha mRNA expressions for the urea SCR emission showed a tendency to increase compared to those of the conventional emission. Thus, gene analysis results suggested that NO(2) from the urea SCR emission affected the expressions of mRNAs in lungs. However, as a whole, the results suggested that the health effects of the urea SCR emission might be less than the conventional emission on rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Air Pollutants, Occupational; Air Pollution; Animals; Bronchoalveolar Lavage Fluid; Catalysis; Deoxyguanosine; Dithiothreitol; Lung; Male; Nitrogen Dioxide; Oligonucleotide Array Sequence Analysis; Organ Size; Oxidants, Photochemical; Oxidative Stress; Particulate Matter; Rats; Rats, Inbred F344; RNA, Messenger; Sulfhydryl Reagents; Trachea; Urea; Vehicle Emissions; Weight Gain

The tolerable level of dietary quercetin for exerting its antioxidative effect was evaluated in high cholesterol-fed rats, using quercetin-containing diets (31-1260 mg quercetin/kg body weight/day) and onion diets (19-94 mg quercetin aglycone equivalent/kg body weight/day), from the viewpoint of a safety assessment. After feeding for 4 weeks, the urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels of the quercetin-containing diet groups fed more than 157 mg quercetin/kg body weight/day were higher than the group fed a quercetin-free diet, although the plasma quercetin metabolite levels and plasma antioxidative activity were elevated depending on the amounts of quercetin or onion diet intake. No significant effect on body weight gain by quercetin-containing diets or onion diets was observed. However, ratios of the liver and kidney weights to the body weight were significantly increased in the quercetin-containing diet groups fed more than 314 mg and 157 mg quercetin/kg body weight/day, respectively, and in the onion diet groups fed more than 47 mg quercetin aglycone equivalent/kg body weight/day. These results indicated that the tolerable level for dietary quercetin for exerting its antioxidative effect was between 126 and 157 mg/kg/day for the quercetin diet and between 19 and 34 mg/kg/day for the onion diet.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Oral; Animal Feed; Animals; Antioxidants; Cholesterol, Dietary; Deoxyguanosine; Hypercholesterolemia; Kidney; Lipid Metabolism; Lipids; Liver; Male; Onions; Organ Size; Oxidative Stress; Plant Extracts; Quercetin; Rats; Rats, Wistar; Weight Gain

Tissue accumulation of advanced glycation end products (AGEs) is associated with ageing, both in diabetics and nondiabetic subjects.. The purpose of this study was to assess immunostaining for AGEs, specifically carboxymethyl-lysine (CML) and receptor for AGEs (RAGE), in muscle tissue of healthy male subjects differing in age and weight stability.. Muscle tissue was obtained during hernia surgery in middle-aged men reporting weight maintenance (WM, n = 10) or weight gain (WG, n = 7), and also in 4 elderly men. Tissue inmunostaining for CML and RAGE was performed.. Intensity of CML and RAGE staining were highly correlated (r = 0.84) and also significantly associated with weight change and age. Muscle AGEs accretion was statistically associated with muscle expression of oxidative injury (8-hydroxy-deoxyguanosine and 4-hydroxy-2-nonenal) and inflammatory markers (tumor necrosis factor-alpha).. The increase of skeletal muscle AGEs/RAGE and markers of inflammation and oxidative injury in association with weight gain and old age suggest a pathogenic role of AGEs in weight gain and in sarcopenia of aging.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Biomarkers; Deoxyguanosine; Glycation End Products, Advanced; Humans; Immunohistochemistry; Inflammation; Male; Middle Aged; Muscle, Skeletal; Oxidation-Reduction; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Tumor Necrosis Factor-alpha; Weight Gain

Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance.. During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported <4kg increase, and weight gainers (WG) reported >5kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-alpha, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66-101yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-alpha and IL-6) were obtained.. 8OHdG was higher in WG compared with WM (149.1+/-16.2 versus 117.8+/-29.5, P=0.03), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9+/-7.6 versus 9.8+/-6.3) but noticeably higher in elderly subjects (21.5+/-15.3, P=0.059). TNF-alpha protein in WG was higher compared with WM (114.0+/-41.7 versus 70.1+/-23.3, P=0.025), and was associated with weight increase.. Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Aging; Aldehydes; Case-Control Studies; Deoxyguanosine; DNA Damage; Humans; Immunohistochemistry; Inflammation; Male; Middle Aged; Muscle, Skeletal; Obesity; Tumor Necrosis Factor-alpha; Weight Gain

The aim was to assess the developmental and biochemical effects resulting from separate and combined exposures to radiation and noise in adult male Sprague-Dawley rats. For 21 days, animals were exposed daily (1) to whole-body 121 kVp X-ray exposure (cumulative dose=5 Gy), (2) to random intermittent noise band-limited between 0.4 and 20 kHz; 2 h day(-1) 86 decibels (dB) and (3) to combined exposures. Control animals were housed under ambient noise conditions 55 dB A-weighted (dBA) and sham-exposed to X-rays. Body weight gain was significantly reduced in animals exposed to either X-rays or noise, and the loss was more pronounced in animals exposed to both conditions. Neither plasma adrenocorticotropic hormone (ACTH) nor corticosterone was altered by the treatment conditions. This study corroborated previous reports that ionizing radiation exposure increased plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHDG), but no effect was observed in animals co-exposed to chronic noise. Plasma big-endothelin-1 (Big ET-1) was significantly reduced in animals exposed to a combination of noise and X-rays. The results indicated that (1) adaptation to chronic noise appeared to occur at the level of the hypothalamic pituitary adrenal (HPA) response, in spite of a compromise in overall body weight gain; and (2) ionizing radiation exposure might alter systems activated by stressor exposure and/or act independently to influence health outcomes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenal Glands; Adrenocorticotropic Hormone; Animals; Corticosterone; Deoxyguanosine; Endothelin-1; Male; Noise; Rats; Rats, Sprague-Dawley; Weight Gain; X-Rays

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, and its metabolites have been reported to protect against oxidative DNA damage in vitro. Streptozotocin (STZ) has drawn attention as a potential source of oxidative stress that induces genotoxicity. In order to elucidate the antioxidative effects of fluvastatin in vivo, we investigated the effects of 7-day treatment with fluvastatin on DNA damage in STZ-treated mice, as well as the effects of the main fluvastatin metabolites (M2, M3 and M4) and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects against DNA damage in the liver and kidney from STZ-treated mice were assessed by the single-cell gel electrophoresis assay, and by detecting 8-hydroxy-2'-deoxyguanosine. A single intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and also caused DNA damage in the liver and kidney. Fluvastatin and its metabolites prevented the STZ-induced elevation of DNA damage and inhibited the increase in serum levels of AST, ALT and BUN. Fluvastatin and its metabolites showed protective effects against DNA damage as potent as that of the reference antioxidants (ascorbic acid, trolox and probucol) though pravastatin and simvastatin still lacked protective activity. Fluvastatin protected the mice against STZ-induced DNA damage, and may reduce the risk of oxidative stress in vivo.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Blood Glucose; Blood Urea Nitrogen; Creatinine; Deoxyguanosine; Diabetes Mellitus, Experimental; DNA; DNA Damage; Fatty Acids, Monounsaturated; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney; Liver; Male; Mice; Mice, Inbred ICR; Oxidative Stress; Pravastatin; Simvastatin; Weight Gain

Heterocyclic aromatic amines (HAA) are initiating agents of colon carcinogenesis in animals and are suspected in the aetiology of human colon cancer. In the context of prevention, it seems interesting to test possible protective compounds, such as fermented milk, against HAA food carcinogens. Male F344 rats were used in a model of HAA-induced colon carcinogenesis. The HAA, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (ratio 1:1:1) were administered in food for a 7 week induction period, with a cumulative dose of 250 mg of the HAA, per kg body weight. Four different diets were given to four rat groups: supplemented with 20% water, 30% non-fermented milk, 30% Bifidobacterium animalis DN-173 010 fermented milk and 30% Streptococcus thermophilus DN-001 158 fermented milk. Fecal mutagenicity was quantified during the induction period. At the end of the treatment, DNA lesion levels were determined in the liver and colon using the number of 8-oxo-7,8-dihydro-2'desoxyguanosine (8-oxodGuo) oxidized bases, "3D Test" and comet assay. The metabolic activity of hepatic and colon cytochrome P450 (CYP450) 1A1 and 1A2 was also evaluated. Aberrant colon crypts were scored, 8 weeks after the last HAA treatment. The results showed that dairy products decreased the incidence of aberrant crypts in rats: 66% inhibition with the milk-supplemented diet, 96% inhibition with the B.animalis fermented milk-supplemented diet and 93% inhibition with the S.thermophilus fermented milk-supplemented diet. Intermediate biomarkers showed that there was a decrease in HAA metabolism, fecal mutagenicity and colon DNA lesions. These results demonstrate the early protective effect of milk in the carcinogenesis process. This effect being more pronounced in the case of milk fermented by lactic acid bacteria.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers, Tumor; Colon; Colonic Neoplasms; Comet Assay; Dairy Products; Deoxyguanosine; Diet; DNA Damage; Feces; Fermentation; Heterocyclic Compounds; Liver; Male; Milk; Mutagenesis; Rats; Rats, Inbred F344; Weight Gain

Mitochondrial damage in rat liver induced by chronic vitamin A-deficiency was studied using three different groups of rats: (i) control rats, (ii) rats fed a vitamin A-free diet until 50 d after birth and (iii) vitamin A-deficient rats re-fed a control diet for 30 d. No statistical difference in body weight and food intake was found between control and vitamin A-deficient rats. Liver GSH concentration was similar in both groups. However, in vitamin A-deficient rats, the mitochondrial GSH/GSSG ratio was significantly lower and the levels of malondialdehyde (MDA) and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (oxo8dG) were higher when compared to control rats. These values were partially restored in re-fed rats. The mitochondrial membrane potential of vitamin A-deficient rats was significantly lower than in control rats and returned to normal levels in restored vitamin A rats. Two populations of mitochondria were found in vitamin A-deficient rats according to the composition of membrane lipids. One population showed a similar pattern to the control mitochondria and the second population had a higher membrane lipid content. This report emphasizes the protective role of vitamin A in liver mitochondria under physiological circumstances.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Animals; Deoxyguanosine; Energy Intake; Female; Flow Cytometry; Glutathione; Glutathione Disulfide; Intracellular Membranes; Malondialdehyde; Membrane Lipids; Membrane Potentials; Mitochondria, Liver; Rats; Vitamin A; Vitamin A Deficiency; Weight Gain