Oxidative cell damage has been linked to the pathogenesis of numerous diseases such as atherosclerosis, type 2 diabetes, and cancer. The consumption of foods rich in polyphenols (e.g. anthocyanins) has been shown to exert preventive effects against such diseases. We investigated the biological effects of anthocyanin-rich fruit juice in a 9-week, placebo-controlled intervention study with 57 healthy male volunteers. The study design encompassed an initial 1 week of wash-out, followed by 8 weeks of intervention period with anthocyanin-rich fruit juice or placebo. The anthocyanin-rich fruit juice demonstrated DNA-protective and antioxidant effects; however, the placebo beverage, rich in vitamin C, showed similar effects based on the tested biomarkers. A significant reduction in background and total DNA strand breaks was observed in both groups within 24 h as well as after 8 weeks of intervention. Only anthocyanin-rich fruit juice consumption provided a significant reduction in body fat and an increase in fat-free mass. The activity of superoxide dismutase (SOD) was significantly elevated after consumption of anthocyanin-rich fruit juice. Both groups showed decreased levels of LDL and total cholesterol (TC) within the first week of the intervention. Similar results in both groups could be explained by the relatively high vitamin C contents of both beverages (>500 mg/L), which may have masked the effects of anthocyanins and other antioxidants in the studied juice. Taken together, anthocyaninrich fruit juice as well as the placebo drink, both of which had high vitamin C content, can improve DNA integrity and might influence lipid metabolism in humans.

Background/Aims: From invertebrates to mammals, Gα_i proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gα_i3-deficiency in pre-hearing murine cochleae pointed to a role of Gα_i3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary (“hair”) bundle, a requirement for the progression of mature hearing. We found that the lack of Gα_i3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear. Methods: Here, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gα_i proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gα_i isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons. Results: Here we report that lack of Gα_i3 but not of the ubiquitously expressed Gα_i2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gα_i2 or Gα_i3 had no impact. In contrast, double-deficiency for Gα_i2 and Gα_i3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gα_i3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gα_i3 is selectively involved in generation of neural gain during auditory processing. Conclusion: We propose a so far unrecognized complexity of isoform-specific and overlapping Gα_i protein functions particular during final differentiation processes.

No abstract

Evidence has been provided that diet and environmental factors directly influence epigenetic mechanisms associated with cancer development in humans. The inhibition of histone deacetylase (HDAC) activity and the disruption of the HDAC complex have been recognized as a potent strategy for cancer therapy and chemoprevention. In the present study, we investigated whether selected plant constituents affect HDAC activity or HDAC1 protein status in the human colon carcinoma cell line HT29. The polyphenols (−)-epigallocatechin-3-gallate (EGCG) and genistein (GEN) as well as two oxidative methyleugenol (ME) metabolites were shown to inhibit HDAC activity in intact HT29 cells. Concomitantly, a significant decrease of the HDAC1 protein level was observed after incubation with EGCG and GEN, whereas the investigated ME metabolites did not affect HDAC1 protein status. In conclusion, dietary compounds were found to possess promising HDAC-inhibitory properties, contributing to epigenetic alterations in colon tumor cells, which should be taken into account in further risk/benefit assessments of polyphenols and alkenylbenzenes.

Sulfate- and glucuronide-phase II metabolites might contribute to the genotoxic potential of RSV by inhibition of TOPII activity. By deconjugation at the target site RSV-3-Sulf might serve as a pool of the parent compound.