Melatonin and Other Tryptophan Metabolites Produced by Yeasts: Implications in Cardiovascular and Neurodegenerative Diseases

Yeast metabolism produces compounds derived from tryptophan, which are found in fermented beverages, such as wine and beer. Melatonin and serotonin, in particular, may play a significant role due to their bioactivity in humans. Indeed, the former is a neurohormone related to circadiam rhythms, which also has a putative protective effect against degenerative diseases. Serotonin, on the other hand, is a neurotransmitter itself, in addition to being a precursor of melatonin synthesis. This paper summarizes data reported on fermented beverages, to evaluate dietary intake. Additionally, the article reviews observed effects of yeast amino acid metabolites on the prevention of neurodegenerative diseases (Alzheimer’s and Parkinson’s) and angiogenesis, focusing on evidence of the molecular mechanism involved and identification of molecular target

Estimating DXA Total Body Fat Percentage by Lipometer Subcutaneous Adipose Tissue Thicknesses

DXA is an accepted reference method to estimate body composition. However several difficulties in the applicability exist. The equipment is rather expensive, not portable, impractical for measurement of big study populations and it provides a minimal amount of ionizing radiation exposure. The optical device Lipometer (EU Pat.No. 0516251) provides non-invasive, quick, precise and safe measurements of subcutaneous adipose tissue (SAT) layer thicknesses at any site of the human body. Compared to DXA there are some advantages in the Lipometer approach, because this device is portable, quick, not expensive and no radiation is involved. To use these advantages in the field of total body fat% (TBF%) assessment, an acceptable estimation of DXA TBF% by Lipometer SAT thicknesses is necessary, which was the aim of this study. Height, weight, waist and hip circumferences, DXA TBF% and Lipometer SAT thicknesses at fifteen defined body sites were measured in 28 healthy men (age: 33.9 ± 16.6 years) and 52 healthy women (age: 40.1 ± 10.7 years). To estimate Lipometer TBF% stepwise multiple regression analysis was applied, using DXA TBF% as dependent variable. Using the fifteen Lipometer SAT thicknesses together with age, height, weight and BMI as independent variables provided the best estimations of Lipometer TBF% for both genders with strong correlations to DXA TBF% (R=0.985 for males and R=0.953 for females). The limits of agreement were –2.48% to +2.48% for males and –4.28% to +4.28% for females. For both genders we received a bias of 0.00%. The results of this paper extend the abilities of the Lipometer by a precise estimation of TBF% using DXA as »golden standard«

Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects

BACKGROUND: Zeolites are crystalline compounds with microporous structures of Si-tetrahedrons. In the gut, these silicates could act as adsorbents, ion-exchangers, catalysts, detergents or anti-diarrheic agents. This study evaluated whether zeolite supplementation affects biomarkers of intestinal wall permeability and parameters of oxidation and inflammation in aerobically trained individuals, and whether it could improve their performance. METHODS: In a randomized, double-blinded, placebo controlled trial, 52 endurance trained men and women, similar in body fat, non-smokers, 20–50 years, received 1.85 g of zeolite per day for 12 weeks. Stool samples for determination of intestinal wall integrity biomarkers were collected. From blood, markers of redox biology, inflammation, and DNA damage were determined at the beginning and the end of the study. In addition, VO(2max) and maximum performance were evaluated at baseline and after 12 weeks of treatment. For statistical analyses a 2-factor ANOVA was used. RESULTS: At baseline both groups showed slightly increased stool zonulin concentrations above normal. After 12 weeks with zeolite zonulin was significantly (p < 0.05) decreased in the supplemented group. IL-10 increased tendentially (p < 0.1) in the zeolite group. There were no significant changes observed in the other measured parameters. CONCLUSIONS: Twelve weeks of zeolite supplementation exerted beneficial effects on intestinal wall integrity as indicated via decreased concentrations of the tight junction modulator zonulin. This was accompanied by mild anti-inflammatory effects in this cohort of aerobically trained subjects. Further research is needed to explore mechanistic explanations for the observations in this study

5-Hydroxymethylfurfural: A Particularly Harmful Molecule Inducing Toxic Lipids and Proteins?

Introduction: 5-HMF is a molecule found in carbohydrate-rich foods that is associated not only with cancer and anaphylactic reactions, but also with anti-oxidant properties. Questions arose as to whether 5-HMF exhibited a catalytic effect in relation to lipid peroxidation and lipoprotein oxidation in presence of metals and/or radicals. Methods: Peroxynitrite (ONOO&minus;)-induced chemiluminescence and ONOO&minus; nitration of tyrosine residues on BSA using anti-nitro-tyrosine-antibodies were used to measure the protection of 5-HMF against peroxides or nitration compared to vitamin C (VitC). The reductive potential of 5-HMF or VitC on Cu2+ or Fe3 was estimated using the bicinchoninic acid (BCA) or Fenton-complex method. Human plasma was used to measure the generation of malondialdehyde (MDA), 4-hydroxynonenal (HNE), and total thiols after Fe2+/H2O2 oxidation in the presence of different concentrations of 5-HMF or VitC. Finally, Cu2+ oxidation of LDL after 4 h was carried out with 5-HMF or VitC, measuring the concentration of MDA in LDL with the thiobarbituric assay (TBARS). Results: VitC was 4-fold more effective than 5-HMF in scavenging ONOO&minus; to nearly 91.5% at 4 mM, with the exception of 0.16 mM, where the reduction of ONOO&minus; by VitC was 3.3-fold weaker compared to 0.16 mM 5-HMF. VitC or 5-HMF at a concentration of 6 mM inhibited the nitration of tyrosine residues on BSA to nearly 90% with a similar course. While 5-HMF reduced free Fe3+ in presence of phenanthroline, forming Fe2+ (phenantroleine)3 [Fe2+(phe)3] or complexed Cu2+(BCA)4 to Cu+(BCA)4 weakly, VitC was 7- to 19-fold effective in doing so over all the used concentrations (0&ndash;25 mM). A Fe2+&mdash;H2O2 solution mixed with human plasma showed a 6&ndash;10 times higher optical density (OD) of MDA or HNE in the presence of 5-HMF compared to VitC. The level of thiols was significantly decreased in the presence of higher VitC levels (1 mM: 198.4 &plusmn; 7.7 &micro;M; 2 mM: 160.0 &plusmn; 13.4 &micro;M) compared to equal 5-HMF amounts (2562 &plusmn; 7.8 &micro;M or 242.4 &plusmn; 2.5 &micro;M), whereas the usage of lower levels at 0.25 &micro;M 5-HMF resulted in a significant decrease in thiols (272.4 &plusmn; 4.0 &micro;M) compared to VitC (312.3 &plusmn; 19.7 &micro;M). Both VitC and 5-HMF accelerated copper-mediated oxidation of LDL equally: while the TBARS levels from 4 h oxidized LDL reached 137.7 &plusmn; 12.3 nmol/mg, it was 1.7-fold higher using 6 mM VitC (259.9 &plusmn; 10.4 nmol/mg) or 6 mM 5-HMF (239.3 &plusmn; 10.2 nmol/mg). Conclusions: 5-HMF appeared to have more pro-oxidative potential compared to VitC by causing lipid peroxidation as well as protein oxidation

The Influence of N-Acetyl-selenomethionine on Two RONS-Generating Cancer Cell Lines Compared to N-Acetyl-methionine

N-acetyl-selenomethionine (NASeLM), a representative of the selenium compounds, failed to convince in clinical studies and cell cultures that it neither inhibits cancer growth nor has a chemoprotective effect. This study aims to find out whether NASeLM shows a growth-inhibiting property compared to the carrier substance N-Acetyl-L-methionine (NALM) on two different cancer cells, namely Jurkat cells and MTC-SK cells. Methods: Jurkat and MTC-SK cells were cultured in the absence or presence of varying concentrations (0–500 µg/mL) of NASeLM and NALM solutions. After 0, 24, 48, and 72 h, mitochondrial activity, cancer cell membrane CP levels, cell growth, and caspase-3 activity were assessed in aliquots of Jurkat and MTC-SK cells. Results: Both substances, NASeLM and NALM, were similarly able to inhibit cell growth and mitochondrial activity of Jurkat cells in a concentration-dependent and time-dependent manner up to 70%. Only the determination of caspase activity showed that only NASeLM was able to increase this to almost 40% compared to the control as well as the same lack of NALM. However, the experiments on MTC-SK cells showed a clear difference in favor of NASeLM compared to NALM. While NASeLM was able to reduce cell growth to up to 55%, the same amount of NALM was only at around 15%, which turned out to be highly significant (p < 0.001). The same could also be measured for the reduction in MTC-SK mitochondrial activity. Time dependence could also be recognized: the longer both substances, NASeLM and NALM, were incubated, the higher the effect on cell growth and mitochondrial activity, in favour of NASeLM. Only NASeLM was able to increase caspase-3 activity in MTC-SK cells: at 250 µg/mL NASeLM, caspase-3 activity increased significantly to 28% after 24 and 48 h compared to the control (14%) or the same NALM concentration (14%). After 72 h, this could still increase to 37%. A further increase in the NASeLM concentration did not result in higher caspase-3 activity. Conclusion: NASeLM could clearly increase caspase-3 activity in both cell types, Jurkat or MTC-SK cells, and thus induce cell death. NALM and NASeLM showed a reduction in cell growth and mitochondrial activity in both cell lines: While NALM and NASeLM showed almost identical measurements on Jurkat cells, NASeLM was much more effective on MTC-SK than the non-selenium-containing carrier, indicating that it has additional anti-chemoprotective effects

Alpha-Ketoglutarate: A Potential Inner Mitochondrial and Cytosolic Protector against Peroxynitrite and Peroxynitrite-Induced Nitration?

The generation of peroxynitrite (ONOO−) is associated with several diseases, including atherosclerosis, hypertension, neurodegeneration, cancer, inflammation, and sepsis. Alpha-ketoglutarate (αKG) is a known potential highly antioxidative agent for radical oxidative species such as peroxides. The question arises as to whether αKG is also a potential scavenger of ONOO− and a potential protector against ONOO−-mediated nitration of proteins. NMR studies of 1 mM αKG in 100 mM phosphate-buffered saline at pH 7.4 and pH 6.0 were carried out in the presence or absence of a final concentration of 2 mM ONOO−. An ONOO−–luminol-induced chemiluminescence reaction was used to measure the scavenging function of several concentrations of αKG; quantification of αKG was performed via spectrophotometric enzymatic assay of αKG in the absence or presence of 0, 1, or 2 mM ONOO−. The nitration of tyrosine residues on proteins was measured on ONOO−-treated bovine serum albumin (BSA) in the presence or absence of 0–24 mM αKG by an ELISA technique using a specific anti-IgG against nitro-tyrosine. The addition of ONOO− to αKG led to the formation of succinic acid and nitrite at pH 7.0, but not at pH 6.0, as αKG was stable against ONOO−. The absorbance of enzymatically estimated αKG at the time point of 30 min was significantly lower in favour of ONOO− (1 mM: 0.21 ± 0.03, 2 mM: 0.12 ± 0.05 vs. 0 mM: 0.32 ± 0.02; p &lt; 0.001). The luminol technique showed an inverse logarithmic correlation of the ONOO− and αKG concentrations (y = −2 × 105 ln(x) + 1 × 106; r2 = 0.99). The usage of 4 mM αKG showed a significant reduction by nearly half in the chemiluminescence signal (284,456 ± 29,293 cps, p &lt; 0.001) compared to the control (474,401 ± 18,259); for 20 and 200 mM αKG, there were further reductions to 163,546 ± 26,196 cps (p &lt; 0.001) and 12,658 ± 1928 cps (p &lt; 0.001). Nitrated tyrosine residues were estimated using the ELISA technique. A negative linear correlation was obtained by estimating nitrated tyrosine residues in the presence of αKG (r2 = 0.94): a reduction by half of nitrated tyrosine was estimated using 12 mM αKG compared to the control (326.1 ± 39.6 nmol vs. 844.5 ± 128.4 nmol; p &lt; 0.001)