RESUMO
A potential contribution of H. pylori contamination to low-grade inflammation, oxidative stress (OS) and insulin resistance as well as correlations between these parameters in asymptomatic sedentary males was analysed. We enrolled 30 apparently healthy asymptomatic young subjects (18 H. pylori negative and 12 positive) and measured whole blood glucose, glycated haemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, TNF-alpha and comet assay. As markers of OS, we used urine levels of iso-PGF2-α and 1,4-dihydroxynonane mercapturic acid (DHN-MA). Twofold elevation of fasting insulin level and HOMA index in H. pylori-positive subjects (p < .05) was shown. Inflammatory parameters and monocyte DNA damage, urine levels of DHN-MA and iso-PGF2-α did not show significant differences between the groups. The early stage of H. pylori-triggered metabolic derangements in sedentary subjects include development of insulin resistance in H. pylori-positive subjects; however, there is no evidence of systemic inflammatory and OS-related changes.
Assuntos
Doenças Assintomáticas , Dinoprosta/análogos & derivados , Helicobacter pylori/fisiologia , Resistência à Insulina , Comportamento Sedentário , Adulto , Biomarcadores/metabolismo , Dinoprosta/urina , Humanos , Inflamação/metabolismo , Masculino , Adulto JovemRESUMO
Xanthohumol (XN) is a hop flavonoid contained in beers and soft drinks. In vitro and animal studies indicated that XN has DNA and cancer protective properties. To find out if it causes DNA protective effects in humans, an intervention trial was conducted in which the participants (n = 22) consumed a XN containing drink (12 mg XN/P/d). We monitored prevention of DNA damage induced by representatives of major groups of dietary carcinogens [i.e., nitrosodimethylamine (NDMA) benzo(a)pyrene (B(a)P) and the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)]. Lymphocytes were collected before, during, and after the intervention and incubated with the carcinogens and with human liver homogenate (S9). We found substantial reduction of B(a)P and IQ (P < 0.001 for both substances) induced DNA damage after consumption of the beverage; also, with the nitrosamine a moderate, but significant protective effect was found. The results of a follow-up trial (n = 10) with XN pills showed that the effects are caused by the flavonoid and were confirmed in γH2AX experiments. To elucidate the underlying mechanisms we measured several parameters of glutathione related detoxification. We found clear induction of α-GST (by 42.8%, P < 0.05), but no alteration of π-GST. This observation provides a partial explanation for the DNA protective effects and indicates that the flavonoid also protects against other carcinogens that are detoxified by α-GST. Taken together, our findings support the assumption that XN has anticarcinogenic properties in humans. Cancer Prev Res; 10(2); 153-60. ©2016 AACR.
Assuntos
Carcinógenos/toxicidade , Dano ao DNA , Flavonoides/farmacologia , Linfócitos/efeitos dos fármacos , Propiofenonas/farmacologia , Adulto , Estudos Cross-Over , Dieta , Feminino , Humanos , MasculinoRESUMO
SCOPE: Xanthohumol (XN) is a hop flavonoid found in beers and refreshment drinks. Results of in vitro and animal studies indicate that it causes beneficial health effects due to DNA protective, anti-inflammatory, antioxidant, and phytoestrogenic properties. Aim of the present study was to find out if XN causes alterations of health-related parameters in humans. METHODS AND RESULTS: The effects of the flavonoid were investigated in a randomized crossover intervention trial (n = 22) in which the participants consumed a XN drink (12 mg XN/P/day). We monitored alterations of the DNA stability in single cell gel electrophoresis assays in lymphocytes and of several health-related biomarkers. A decrease of oxidatively damaged purines and protection toward reactive oxygen species induced DNA damage was found after the consumption of the beverage; also the excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-guanosine in urine was reduced. The assumption that the flavonoid causes DNA protection was confirmed in a randomized follow-up study with pure XN (n = 10) with a parallel design. Other biochemical parameters reflecting the redox- and hormonal status and lipid- and glucose metabolism were not altered after the intervention. CONCLUSION: Taken together, our data indicate that low doses of XN protect humans against oxidative DNA damage.
Assuntos
DNA/efeitos dos fármacos , Flavonoides/farmacologia , Propiofenonas/farmacologia , Substâncias Protetoras/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Adulto , DNA/química , Dano ao DNA/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Flavonoides/sangue , Humanos , Masculino , Propiofenonas/sangue , Análise de Célula Única/métodosRESUMO
INTRODUCTION: Sedentary lifestyle is a major risk factor for diabetes, cardiovascular and many other age-related diseases. Heart rate variability (HRV) reflects the function of regulatory systems of internal organs and may sensitively indicate early metabolic disturbances. We hypothesize that quantitative and qualitative changes of HRV in young subjects may reflect early metabolic derangements responsible for further development of clinically significant disease. AIM: The aim of our study was to determine whether the parameters of carbohydrate metabolism (fasting blood glucose, HBA1c and surrogate insulin sensitivity/resistance indices) correlate with anthropometric data and HRV. METHODS: The study group consisted of 30 healthy sedentary male subjects aged 20-40, nonsmokers, mainly office and research employees, medical staff and students. Athletes, actively training more than one hour per week, severely obese and men of physical work were excluded from the study. HRV parameters were derived from short term ECG records (five minutes intervals) in supine position and during orthostatic test. Anthropometric data included height, weight, body mass index (BMI), age and body composition (estimation by bioelectric impedance method). The fasting blood glucose, insulin and C-peptide, homeostatic model assessment (HOMA-IR) index and glycated hemoglobin (HbA1c) were evaluated. Linear correlation coefficient (r) was calculated using Statistica 10.0 software. RESULTS AND DISCUSSION: HOMA-IR index correlated positively with body weight, visceral fat and BMI (p=0.047, 0.027 and 0.017 respectively). In supine position pNN50 positively correlated with glucose/insulin ratio (p=0.011) and heart rate with HOMA-IR (p=0.006). In orthostatic test negative correlations of HBA1c with standard deviation, total and low frequency power were determined (p=0.034, 0.400 and 0.403 respectively), which indicates a gradual worsening of functional capacity of cardiovascular system with low-grade increase (under the conventional threshold) of HBA1c. CONCLUSIONS: In apparently healthy sedentary subjects HRV reduction correlates with the age advancement, subclinical deteriorations of carbohydrate metabolism and excessive fat accumulation.