8-hydroxy-2--deoxyguanosine and Weight-Loss

Obesity may induce oxidative stress, causing oxidative damage of DNA. We examined associations between decreasing serum and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and weight loss in morbidly obese patients before and 6 months after laparoscopic adjustable gastric banding (LAGB).. We compared patients who had surgery for morbid obesity with healthy, nonobese controls. Urine and fasting blood samples were collected once from the controls and from the morbidly obese patients before and 6 months after the LAGB. The serum and urinary 8-OHdG levels were evaluated in these groups using an enzyme-linked immunosorbent assay kit.. We included 20 patients who had surgery for morbid obesity (8 men, 12 women, mean body mass index [BMI] 46.82 ± 4.47) and 20 healthy, nonobese people (10 men, 10 women, mean BMI 22.52 ± 2.08) in our study. There was no significant difference in serum 8-OHdG levels between the groups, whereas urinary 8- OHdG levels were significantly higher in morbidly obese patients than in controls. Weight, BMI and serum and urinary 8-OHdG levels were significantly decreased in morbidly obese patients 6 months after LAGB.. The LAGB provides efficient weight loss in patients with morbid obesity. The systemic oxidative DNA damage was increased by the morbid obesity, but this increase was not related to weight gain, and it was more evident in serum than urine samples. After LAGB for morbid obesity, the oxidative DNA damage declined both in serum and urine.. L’obésité peut provoquer stress oxydatif qui endommage l’ADN. Nous avons analysé les liens entre une baisse des taux de 8-OHdG (8-hydroxy-2’-désoxyguanosine) sériques et urinaires et la perte de poids chez des patients atteints d’obésité morbide avant, puis 6 mois après la pose d’un anneau gastrique ajustable par laparoscopie (AGAL).. Nous avons comparé des patients qui ont subi cette chirurgie pour un problème d’obésité morbide à des témoins non obèses en bonne santé. Nous avons prélevé des échantillons d’urine et de sang à jeun chez les témoins 1 fois et chez les patients atteints d'obésité morbide, avant, puis 6 mois après l’intervention pour AGAL. Les taux de 8-OHdG sériques et urinaires ont été mesurés dans les 2 groupes à l’aide d’une trousse de test ELISA (enzyme-linked immunosorbent assay).. Notre étude a inclus 20 patients soumis à la chirurgie pour obésité morbide (8 hommes, 12 femmes; indice de masse corporelle [IMC] moyen 46,82 ± 4,47) et 20 témoins non obèses en bonne santé (10 hommes, 10 femmes; IMC moyen 22,52 ± 2,08). Nous n’avons noté aucune différence significative des taux de 8-OHdG sériques entre les 2 groupes, mais les taux de 8-OHdG urinaires étaient significativement plus élevés chez les patients souffrant d’obésité morbide que chez les témoins. Le poids, l’IMC et les taux de 8-OHdG sériques et urinaires avaient significativement diminué chez les patients atteints d’obésité morbide 6 mois après l’intervention pour AGAL.. L’AGAL est une technique efficace de perte de poids chez les patients souffrant d’obésité morbide. L’atteinte oxydative systémique de l’ADN était exacerbée par l’obésité morbide, mais cette hausse n’était pas reliée au gain pondéral, et elle était plus évidente dans les échantillons sériques que dans les échantillons urinaires. Après la pose d’un AGAL pour obésité morbide, l’atteinte oxydative de l’ADN a diminué dans le sérum et dans l’urine.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Deoxyguanosine; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Gastroplasty; Humans; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Oxidative Stress; Treatment Outcome; Weight Loss

Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation. In order to better understand the role of Se in epithelial injury and tumorigenesis resulting from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or -sufficient mice in response to dextran sodium sulfate (DSS)-induced colitis, and azoxymethane (AOM) followed by cyclical administration of DSS, respectively. In response to DSS alone, Se-deficient mice demonstrated increased morbidity, weight loss, stool scores, and colonic injury with a concomitant increase in DNA damage and increases in inflammation-related cytokines. As there was an increase in DNA damage as well as expression of several EGF and TGF-β pathway genes in response to inflammatory injury, we sought to determine if tumorigenesis was altered in the setting of inflammatory carcinogenesis. Se-deficient mice subjected to AOM/DSS treatment to model colitis-associated cancer (CAC) had increased tumor number, though not size, as well as increased incidence of high grade dysplasia. This increase in tumor initiation was likely due to a general increase in colonic DNA damage, as increased 8-OHdG staining was seen in Se-deficient tumors and adjacent, non-tumor mucosa. Taken together, our results indicate that Se deficiency worsens experimental colitis and promotes tumor development and progression in inflammatory carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Azoxymethane; Carcinogenesis; Colitis; Colonic Neoplasms; Deoxyguanosine; Dextran Sulfate; Diet; DNA Damage; Epidermal Growth Factor; Gene Expression Regulation; Inflammation; Mice; Mice, Inbred C57BL; Selenium; Signal Transduction; Transforming Growth Factor beta; Weight Loss

The effect of stress associated with acute weight reduction on adipocytokine production is incompletely understood. In the present study, we have investigated the changes in circulating adipocytokine concentrations and urinary concentrations of stress markers in male collegiate wrestlers during acute weight reduction for a competition. Twenty healthy Japanese male wrestlers (18-22 years of age) who participated in the national collegiate wrestling tournament were studied. Body weight, body fat amount, serum testosterone, serum leptin, serum adiponectin, urinary 8-hydroxy-2'- deoxyguanosine (8-OHdG) and urinary biopyrrins were analyzed during acute weight reduction for the competition. Body weight, body fat amount and the serum concentrations of testosterone, leptin and adiponectin significantly decreased on the day of weigh-in compared with the levels 12 days before weigh-in. In contrast, urinary concentrations of 8-OHdG and biopyrrins significantly increased on the day of weigh-in compared with the concentrations 12 days before weigh-in. A positive correlation was observed between the serum concentrations of adiponectin and testosterone, and a negative correlation was observed between the concentrations of serum adiponectin and urinary biopyrrins. The present results suggest that rapid weight reduction increases the urinary concentrations of stress markers, which is associated with a decrease in serum concentrations of adiponectin.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adiponectin; Adiposity; Adolescent; Adult; Bilirubin; Biomarkers; Deoxyguanosine; Humans; Leptin; Male; Oxidative Stress; Testosterone; Weight Loss; Wrestling

Flumequine (FLU), an anti-bacterial quinolone agent, has been recognized as a non-genotoxic carcinogen for the mouse liver, but recent reports have suggested that some genotoxic mechanism involving oxidative DNA damage may be responsible for its hepatocarcinogenesis. In the present study, we investigated this possibility in the mouse liver using male and female B6C3F1 gpt delta mice fed diet containing 0.4% FLU, a carcinogenic dose, for 13 weeks. Measurements of 8-hydroxydeoxyguanosine levels in liver DNA, and gpt point and deletion mutations revealed no significant increases in any of these parameters in either sex. Histopathologically, centrilobular swelling of hepatocytes with vacuolation was apparent, however, together with significant increase in bromodeoxyuridine-labeling indices in the treated males and females. These results suggest that genotoxicity, including oxidative DNA damage, is not involved in mouse hepatocarcinogenesis by FLU, which might rather solely exert tumor-promoting effects in the liver.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anti-Infective Agents; Bromodeoxyuridine; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA; DNA Damage; Eating; Escherichia coli Proteins; Female; Fluoroquinolones; Hepatocytes; Immunochemistry; Liver; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Transgenic; Mutagenicity Tests; Mutation; Organ Size; Pentosyltransferases; Weight Loss

Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. It consists of the following five crude drugs: Cinnamomi Cortex, Poria, Moutan Cortex, Persicae Semen and Paeoniae Radix. In this study, the effects of keishibukuryogan against renal damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of keishibukuryogan significantly attenuated urinary protein excretion and serum creatinine levels. It did not affect body weight loss and blood glucose levels, but it suppressed renal and hepatic weights of WBN/Kob rats. Keishibukuryogan also reduced fibronectin and transforming growth factor beta(1) (TGF-beta(1)) protein expression in the renal cortex. Furthermore, lipid peroxidation levels in both kidney and liver were significantly lower than those of untreated control WBN/Kob rats. Urinary excretion of 8-hydroxy-deoxyguanosine was suppressed by keishibukuryogan treatment. These results suggest that keishibukuryogan reduces oxidative stress by hyperglycemia, and that it protects renal function and suppresses fibronectin deposition induced by TGF-beta(1) production in WBN/Kob rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Creatinine; Deoxyguanosine; Diabetes Mellitus, Experimental; Drugs, Chinese Herbal; Fibronectins; Hyperglycemia; Kidney; Lipid Peroxidation; Male; Medicine, Traditional; Organ Size; Oxidative Stress; Phytotherapy; Plant Preparations; Protective Agents; Proteinuria; Rats; Rats, Wistar; Transforming Growth Factor beta1; Weight Loss

The most noticeable hypothesis regarding the pathogenesis of cisplatin toxicity, seen mainly in kidney and intestine, is oxidative stress, an imbalance between free-radical generating cisplatin and radical scavenging systems. This paper describes the role of the antioxidant system in cisplatin-induced toxicity and the protective effect by a processed grain food (Antioxidant Biofactor: AOB), which has been shown to exhibit strong antioxidant activity. Male Fischer 344 rats were used. They were pre-fed either a basal diet (control, 15 g/day) or the diet supplemented with AOB to provide 6.5% or 20% of total diet throughout the experiment. Cisplatin (5 mg/kg, i.v.) was administered at the start of the experiment, and the animals were sacrificed 5 days later. Blood urea nitrogen (BUN) and plasma creatinine, NO2(-) and NO3(-) (NOx) were determined from the plasma. The levels of 4-hydroxy-2-nonenal (a lipid peroxidation product), 8-hydroxy-deoxyguanosine (8-OHdG, an oxidatively modified DNA adduct) and nitrotyrosine were histologically analyzed. The cisplatin administration resulted in a loss of body weight and elevations of BUN, serum creatinine and NOx levels, whereas AOB supplement reversed these effects. The severe morphological damages induced in the kidney and intestine by the cisplatin administration were markedly improved in the AOB group. The levels of lipid peroxidation, 8-OHdG, and nitrotyrosine all paralleled the morphological damage. The AOB effect was dose dependent. In conclusion, the present study suggests that certain food additives like AOB may be of benefit against the side effects of cisplatin.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Antioxidants; Blood Urea Nitrogen; Cisplatin; Creatinine; Deoxyguanosine; Diet; Edible Grain; Fermentation; Intestines; Kidney; Lipid Peroxidation; Male; Nitrates; Nitrites; Rats; Rats, Inbred F344; Tyrosine; Weight Loss

In the present study we demonstrated the protective effects of the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) against fulminant hepatitis with jaundice in LEC rats. In LEC rats an excess amount of copper is accumulated in the liver and causes hepatitis with severe jaundice. PBN was subcutaneously administered every 2 d at the concentration of 128 mg/kg, beginning with 13-week-old rats and continuing for 17 weeks. PBN prevented the loss of body weight, reduced death rate, and suppressed the increase in GTP and GOT values reflecting hepatic cell destruction. Ocular inspection also confirmed the suppressive effects of PBN on jaundice. In parallel with these phenomena, the amounts of thiobarbituric acid-reactive substances (TBARS) in livers of PBN-administered rats were found to be lower than those of non-PBN-administered rats. Little histological changes were observed in PBN-administered rats in comparison with non-PBN-administered rats. The protective effect of PBN on the formation of oxidative damage in liver DNA was observed but not so remarkable as that on lipid peroxidation. From these results, it was concluded that PBN had the liver-protective effects against fulminant hepatitis with jaundice. This suggested that free radicals play an important role in abnormally accumulated copper-induced liver injury and that PBN potentially has therapeutic value for the treatment of hepatitis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Alanine Transaminase; Animals; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Copper; Cyclic N-Oxides; Deoxyguanosine; DNA; Jaundice; Lipid Peroxidation; Liver; Nitrogen Oxides; Rats; Rats, Mutant Strains; Spin Labels; Thiobarbituric Acid Reactive Substances; Weight Loss