Abstract
B61
Patients with chronic renal failure undergoing hemodialysis (HD) face an elevated risk for cancer, artheriosclerosis and other diseases. Factors considered to contribute to such increased health risks include oxidative stress exerted in several ways by the extracorporal blood circuit, but also malnutrition and iron supplementation. A red fruit juice with especially high flavonoid/ polyphenol content previously has been found by us to diminish oxidative cell damage in healthy probands (Weisel et al. Biotechnol. J., 1, 388, 2006). In HD-patients this juice was highly effective as well: In a ten week intervention study with 21 subjects (three week run-in phase (R), four week 200 ml/d juice-uptake (J), three week wash-out phase (W), weekly blood samplings) markedly reduced DNA oxidation damage, protein oxidation, lipid peroxidation and NFκB-DNA binding activity were observed concomitant with significantly elevated glutathione level/status in blood (Spormann et al., Arch. Pharmacol.; 375, 1, 95, 2007).
To evaluate effects on antioxidant genes in a subset of the HD-patients, RNA was isolated from lymphocytes obtained from the blood samplings and gene expression measured by Real-Time TaqMan PCR. Target genes studied where γ-glutamate-cysteine ligase (γ-GCl, catalytic, GCLC and modulatory, GCLM subunits); encoding the enzyme which catalyzes the rate limiting step of glutathione synthesis, glutathione peroxidase 1 (GPX1), glutathione reductase (GSR) and the transcription factor Nrf2 (NF-E2-related factor 2). NFκB regulated cycloxygenase 2 (Cox-2), which plays a pivotal role in inflammatory processes, was also included. Results obtained from 11 patients show a significant induction of both γ-GCL subunits during juice uptake. In the subsequent wash-out phase, GCLC transcription decreased, whereas transcription of GCLM remained elevated. Distinct juice dependent induction of GPX1 and Nrf2 gene expression was also observed, whereas GSR transcription was at best slightly elevated. For Cox-2, the results show a depletion of mRNA transcripts during juice uptake.
In conclusion, the juice intervention clearly lead to elevated transcription of antioxidant genes, reduction of oxidative damage and an increase of antioxidant defense in HD-patients. This provides promising perspectives into prevention of cancer and other diseases in population subgroups exposed to enhanced oxidative stress.
(Supported by Karin Nolte Foundation)
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B61.
Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC