The correlations of glycated hemoglobin and carbohydrate metabolism parameters with heart rate variability in apparently healthy sedentary young male subjects

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

Obituary for Tamara Grummt

Tamara Grummt passed away on January 26, 2020 in Oelsnitz/Vogtland, Germany. Tamara was one of the scientific pioneers in the field of environmental toxicology, namely genotoxicity and hygiene of drinking and bathing waters. Her passing is not only a great loss to environmental research and to the global environmental toxicology community—we have lost an outstanding personality with the heart in the right place, who has become, for many of us, a wonderful friend

Antioxidants / Effects of -carotene and its cleavage products in primary pneumocyte type II cells

-Carotene has been shown to increase the risk of developing lung cancer in smokers and asbestos workers in two large scale trails, the Beta-Carotene and Retinol Efficacy Trial (CARET) and the Alpha-Tocopherol Beta-carotene Cancer Prevention Trial (ATBC). Based on this observation, it was proposed that genotoxic oxidative breakdown products may cause this effect. In support of this assumption, increased levels of sister chromatid exchanges, micronuclei, and chromosomal aberrations were found in primary hepatocyte cultures treated with a mixture of cleavage products (CPs) and the major product apo-8′carotenal. However, because these findings cannot directly be transferred to the lung due to the exceptional biotransformation capacity of the liver, potential genotoxic and cytotoxic effects of -carotene under oxidative stress and its CPs were investigated in primary pneumocyte type II cells. The results indicate that increased concentrations of -carotene in the presence of the redox cycling quinone dimethoxynaphthoquinone (DMNQ) exhibit a cytotoxic potential, as evidenced by an increase of apoptotic cells and loss of cell density at concentrations > 10 M. On the other hand, the analysis of micronucleated cells gave no clear picture due to the cytotoxicity related reduction of mitotic cells. Last, although CPs induced significant levels of DNA strand breaks even at concentrations 1 M and 5 M, respectively, -carotene in the presence of DMNQ did not cause DNA damage. Instead, -carotene appeared to act as an antioxidant. These findings are in contrast with what was demonstrated for primary hepatocytes and may reflect different sensitivities to and different metabolism of -carotene in the two cell types.(VLID)219514

Xanthohumol attenuates tumour cell-mediated breaching of the lymphendothelial barrier and prevents intravasation and metastasis

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Adduction to arginine detoxifies aflatoxin B1 by eliminating genotoxicity and altering in vitro toxicokinetic profiles

Aflatoxin B1 (AFB1), a class 1 carcinogen and prominent food contaminant, is highly linked to the development of hepatocellular carcinoma (HCC) and plays a causative role in a large portion of global HCC cases. We have demonstrated that a mixture of common organic acids (citric and phosphoric acid) along with arginine can eliminate >99% of AFB1 in solution as well as on corn kernels and convert it to the AFB2a-Arg adduct, acting as a potential detoxification process for contaminated foods. Evaluation of toxicokinetic changes after AFB2a-Arg formation show that the product is highly stable in biological fluids, is not metabolized by P450 enzymes, is highly plasma protein bound, has low lipid solubility, and has poor intestinal permeability/ high intestinal efflux compared to AFB1. Ames’ test results show that at mutagenic concentrations of AFB1, AFB2a-Arg does not have any measurable mutagenic effect which was confirmed by DNA adduct identification by liquid chromatography-mass spectrometry. Evaluation in HepG2 and HepaRG cells showed that AFB2a-Arg did not cause any significant decreases in cell viability nor did it increase micronuclei formation when administered at toxic concentrations of AFB1. These results show that conversion of AFB1 to AFB2a-Arg is a potential strategy to detoxify contaminated food

Inhalative Exposure to Vanadium Pentoxide Causes DNA Damage in Workers: Results of a Multiple End Point Study

BackgroundInhalative exposure to vanadium pentoxide (V(2)O(5)) causes lung cancer in rodents.ObjectiveThe aim of the study was to investigate the impact of V(2)O(5) on DNA stability in workers from a V(2)O(5) factory.MethodsWe determined DNA strand breaks in leukocytes of 52 workers and controls using the alkaline comet assay. We also investigated different parameters of chromosomal instability in lymphocytes of 23 workers and 24 controls using the cytokinesis-block micronucleus (MN) cytome method.ResultsSeven of eight biomarkers were increased in blood cells of the workers, and vanadium plasma concentrations in plasma were 7-fold higher than in the controls (0.31 microg/L). We observed no difference in DNA migration under standard conditions, but we found increased tail lengths due to formation of oxidized purines (7%) and pyrimidines (30%) with lesion-specific enzymes (formamidopyrimidine glycosylase and endonuclease III) in the workers. Bleomycin-induced DNA migration was higher in the exposed group (25%), whereas the repair of bleomycin-induced lesions was reduced. Workers had a 2.5-fold higher MN frequency, and nucleoplasmic bridges (NPBs) and nuclear buds (Nbuds) were increased 7-fold and 3-fold, respectively. Also, apoptosis and necrosis rates were higher, but only the latter parameter reached statistical significance.ConclusionsV(2)O(5) causes oxidation of DNA bases, affects DNA repair, and induces formation of MNs, NPBs, and Nbuds in blood cells, suggesting that the workers are at increased risk for cancer and other diseases that are related to DNA instability.Veronika A. Ehrlich, Armen K. Nersesyan, Kambis Atefie, Christine Hoelzl, Franziska Ferk, Julia Bichler, Eva Valic, Andreas Schaffer, Rolf Schulte‑Hermann, Michael Fenech, Karl‑Heinz Wagner and Siegfried Knasmüllerhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2599764

Supported ionic liquids for the efficient removal of acetylsalicylic acid from aqueous solutions

Acetylsalicylic acid, commercially available as aspirin, is one of the most used drugs in the world, being detected in several environmental compartments, including drinking water supplies. Given its environmental impact, the development of a cost‐effective technology capable of removing this pharmaceutical from water samples is of high relevance, for which materials based on silica chemically modified with ionic liquids (SILs) can be foreseen as a promising alternative. In this work, four SILs (with the chloride anion and imidazolium or tetraalkylammonium cations of different alkyl side chain length) were synthesized and characterized, and their potential for the adsorption of acetylsalicylic acid appraised by adsorption kinetics and isotherms. Envisioning their use to treat drinking water, the toxicity of all SILs towards the liver cell line Hep2G was determined. The best identified SIL, comprising the dimethylbutylammonium cation, displays a maximum adsorption capacity of 0.08 mmol/g, being 1 g of this material sufficient to treat ca. 14,500 L of water containing 1 μg/L of acetylsalicylic acid (under ideal conditions). Furthermore, this material has a negligible toxicity towards the liver cell line Hep2G. The results obtained reinforce the potential of SILs as alternative adsorbents to effectively remove a cetylsalicylic acid from aqueous solutions, and may be envisioned as a promising strategy for the treatment of wastewater and drinking water.publishe

EGCG Prevents High Fat Diet-Induced Changes in Gut Microbiota, Decreases of DNA Strand Breaks, and Changes in Expression and DNA Methylation of Dnmt1

Obesity as a multifactorial disorder involves low-grade inflammation, increased reactive oxygen species incidence, gut microbiota aberrations, and epigenetic consequences. Thus, prevention and therapies with epigenetic active antioxidants, (-)-Epigallocatechin-3-gallate (EGCG), are of increasing interest. DNA damage, DNA methylation and gene expression of DNA methyltransferase 1, interleukin 6, and MutL homologue 1 were analyzed in C57BL/6J male mice fed a high-fat diet (HFD) or a control diet (CD) with and without EGCG supplementation. Gut microbiota was analyzed with quantitative real-time polymerase chain reaction. An induction of DNA damage was observed, as a consequence of HFD-feeding, whereas EGCG supplementation decreased DNA damage. HFD-feeding induced a higher inflammatory status. Supplementation reversed these effects, resulting in tissue specific gene expression and methylation patterns of DNA methyltransferase 1 and MutL homologue 1. HFD feeding caused a significant lower bacterial abundance. The Firmicutes/Bacteroidetes ratio is significantly lower in HFD + EGCG but higher in CD + EGCG compared to control groups. The results demonstrate the impact of EGCG on the one hand on gut microbiota which together with dietary components affects host health. On the other hand effects may derive from antioxidative activities as well as epigenetic modifications observed on CpG methylation but also likely to include other epigenetic elements