Acrylamide-derived DNA adducts in human peripheral blood mononuclear cell DNA: Correlation with body mass.

Acrylamide (AA) is a carcinogen formed during thermal food processing and can cause tumors in rodents while its carcinogenic potency in humans is unclear. Metabolic conversion of AA leads to glycidamide (GA) forming N7-GA-guanine (N7-GA-Gua) as the major DNA adduct in rodents while no such adducts were found in human tissues so far. In a cohort of 56 healthy volunteers adduct levels were determined in peripheral blood mononuclear cell (PBMC) DNA and anthropometric, dietary, and biochemical parameters were measured or inquired using a questionnaire. In the majority of PBMC DNA samples the levels found were above one adduct/108 nucleosides not being correlated to dietary habits including coffee consumption, or to blood glucose levels or hemoglobin HbA1c. However, adduct levels were significantly correlated with the body mass index (BMI) and showed a continuous increase over three BMI classes. Our findings indicate a background of AA-derived DNA adducts present in humans in PBMC related to body mass rather than to certain dietary or lifestyle factors.

Isomerizing olefin metathesis as a strategy to access defined distributions of unsaturated compounds from fatty acids.

The dimeric palladium(I) complex [Pd(µ-Br)(t)Bu(3)P](2) was found to possess unique activity for the catalytic double-bond migration within unsaturated compounds. This isomerization catalyst is fully compatible with state-of-the-art olefin metathesis catalysts. In the presence of bifunctional catalyst systems consisting of [Pd(µ-Br)(t)Bu(3)P](2) and NHC-indylidene ruthenium complexes, unsaturated compounds are continuously converted into equilibrium mixtures of double-bond isomers, which concurrently undergo catalytic olefin metathesis. Using such highly active catalyst systems, the isomerizing olefin metathesis becomes an efficient way to access defined distributions of unsaturated compounds from olefinic substrates. Computational models were designed to predict the outcome of such reactions. The synthetic utility of isomerizing metatheses is demonstrated by various new applications. Thus, the isomerizing self-metathesis of oleic and other fatty acids and esters provides olefins along with unsaturated mono- and dicarboxylates in distributions with adjustable widths. The cross-metathesis of two olefins with different chain lengths leads to regular distributions with a mean chain length that depends on the chain length of both starting materials and their ratio. The cross-metathesis of oleic acid with ethylene serves to access olefin blends with mean chain lengths below 18 carbons, while its analogous reaction with hex-3-enedioic acid gives unsaturated dicarboxylic acids with adjustable mean chain lengths as major products. Overall, the concept of isomerizing metatheses promises to open up new synthetic opportunities for the incorporation of oleochemicals as renewable feedstocks into the chemical value chain.

Antioxidant-rich coffee reduces DNA damage, elevates glutathione status and contributes to weight control: results from an intervention study.

Epidemiological and experimental evidence increasingly suggests coffee consumption to be correlated to prevention or delay of degenerative diseases connected with oxidative cellular stress. In an intervention study comprising 33 healthy volunteers, we examined DNA-protective and antioxidative effects exerted in vivo by daily ingestion of 750 mL of freshly brewed coffee rich in both green coffee bean constituents as well as roast products. The study design encompassed an initial 4 wk of wash-out, followed by 4 wk of coffee intake and 4 wk of second wash-out. At the start and after each study phase blood samples were taken to monitor biomarkers of oxidative stress response. In addition, body weight/composition and intake of energy/nutrients were recorded. In the coffee ingestion period, the primary endpoint, oxidative DNA damage as measured by the Comet assay (± FPG), was markedly reduced (p<0.001). Glutathione level (p<0.05) and GSR-activity (p<0.01) were elevated. Body weight (p<0.01)/body fat (p<0.05) and energy (p<0.001)/nutrient (p<0.001-0.05) intake were reduced. Our results allow to conclude that daily consumption of 3-4 cups of brew from a special Arabica coffee exerts health beneficial effects, as evidenced by reduced oxidative damage, body fat mass and energy/nutrient uptake.

Anthocyanin/polyphenolic-rich fruit juice reduces oxidative cell damage in an intervention study with patients on hemodialysis.

Hemodialysis patients face an elevated risk of cancer, arteriosclerosis, and other diseases, ascribed in part to increased oxidative stress. Red fruit juice with high anthocyanin/polyphenol content had been shown to reduce oxidative damage in healthy probands. To test its preventive potential in hemodialysis patients, 21 subjects in a pilot intervention study consumed 200 mL/day of red fruit juice (3-week run-in; 4-week juice uptake; 3-week wash-out). Weekly blood sampling was done to monitor DNA damage (comet assay +/- formamidopyrimidine-DNA glycosylase enzyme), glutathione, malondialdehyde, protein carbonyls, trolox equivalent antioxidant capacity, triglycerides, and DNA binding capacity of the transcription factor nuclear factor-kappaB. Results show a significant decrease of DNA oxidation damage (P < 0.0001), protein and lipid peroxidation (P < 0.0001 and P < 0.001, respectively), and nuclear factor-kappaB binding activity (P < 0.01), and an increase of glutathione level and status (both P < 0.0001) during juice uptake. We attribute this reduction in oxidative (cell) damage in hemodialysis patients to the especially high anthocyanin/polyphenol content of the juice. This provides promising perspectives into the prevention of chronic diseases such as cancer and cardiovascular disease in population subgroups exposed to enhanced oxidative stress like hemodialysis patients.

An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands.

Oxidative cell damage is involved in the pathogenesis of atherosclerosis, cancer, diabetes and other diseases. Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols, might reduce oxidative cell damage. Therefore, an intervention study was performed with a red mixed berry juice [trolox equivalent antioxidative capacity (TEAC): 19.1 mmol/L trolox] and a corresponding polyphenol-depleted juice (polyphenols largely removed, TEAC 2.4 mmol/L trolox), serving as control. After a 3-week run-in period, 18 male probands daily consumed 700 mL juice, and 9 consumed control juice, in a 4-week intervention, followed by a 3-week wash-out. Samples were collected weekly to analyze DNA damage (comet assay), lipid peroxidation (plasma malondialdehyde: HPLC/fluorescence; urinary isoprostanes: GC-MS), blood glutathione (photometrically), DNA-binding activity of nuclear factor-kappaB (ELISA) and plasma carotenoid/alpha-tocopherol levels (HPLC-DAD). During intervention with the fruit juice, a decrease of oxidative DNA damage (p<5x10(-4)) and an increase of reduced glutathione (p<5x10(-4)) and of glutathione status (p<0.05) were observed, which returned to the run-in levels in the subsequent wash-out phase. The other biomarkers were not significantly modulated by the juice supplement. Intervention with the control juice did not result in reduction of oxidative damage. In conclusion, the fruit juice clearly reduces oxidative cell damage in healthy probands.

Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in uremic patients.

Uremic patients undergoing hemodialysis (HD) are considered to face an elevated risk for atherosclerosis and cancer. This has been attributed in part to an increased oxidative stress. In this pilot study, oxidative cell damage in blood of HD-patients was compared to those of controls: total DNA damage (basic and specific oxidative DNA damage), modulation of glutathione levels (total and oxidized glutathione) and of lipid peroxidation were monitored via the Comet assay (with and without FPG), a kinetic photometric assay and HPLC quantification of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were analysed for malondialdehyde-deoxyguanosine-adducts (M1dG) with an immunoslot blot technique. HD-patients (n=21) showed a significant increase of total DNA damage (p<10(-12)), compared to controls (n=12). In a subset of patients and controls, GSSG levels and M1dG, however, only increased slightly, while tGSH and MDA levels did not differ. The influence of different low flux HD-membranes was tested in a pilot study with nine patients consecutively dialysed on three membrane types for four weeks each. In addition to the individual disposition of the patient, the dialyser membrane had a significant impact on oxidative stress. Total DNA damage was found to be almost identical for polysulfone and vitamin E coated cellulosic membranes, whereas a slight, but significant increase was observed with cellulose-diacetate (p<0.001). In patients receiving iron infusion during HD, MDA-formation (n=11) and total DNA damage (n=10) were additionally increased (p<0.005). Our results show an increased oxidative damage in HD-patients, compared to healthy volunteers. Significant influences were found for the dialyser membrane type and iron infusion.