Intervention with polyphenol-rich fruit juices results in an elevation of glutathione S-transferase P1 (hGSTP1) protein expression in human leucocytes of healthy volunteers.
Polyphenols are probably antigenotoxic on account of their antioxidant activities and might alter phase I and II enzymes in a way that results in chemoprotection. We investigated the hypothesis that polyphenols enhance expression of glutathione S-transferases (GSTs), which increases carcinogen detoxification and thereby provides protection against oxidative stress. HGSTP1 protein expression and GST polymorphisms were determined in leucocytes obtained during an intervention study with healthy subjects consuming two fruit juices in an 8 wk trial (polyphenol-free run in phase, juice intervention phase, washout phase, second juice intervention phase, each treatment regime lasted for 2 wk). The study had originally shown that juice intervention significantly reduced oxidative DNA damage in leucocytes at week 8 (Bub, A., Watzl, B., Blockhaus, M., Briviba, K. et al., J. Nutr. Biochem. 2003, 14, 90-98). We reanalysed the levels of DNA damage based on GST genotypes. We also treated leucocytes in vitro with mixtures of polyphenols and determined cytotoxicity and expression of 96 genes related to drug metabolism. Key results with leucocytes of the intervention study were that the initial content of hGSTP1 protein was first suppressed at weeks 4 and 6. At week 8, however, hGSTP1 protein expression was significantly increased. HGSTP1 protein levels and DNA damage were inversely correlated (p = 0.005), but there was no difference for cells obtained from subjects with hGSTM1*1 and hGSTM1*0 genotypes, nor was there any difference between cells from subjects consuming the two different juices. The treatment of leucocytes with polyphenol mixtures in vitro did not result in modulated GST gene expression or total GST activity, but in an up-regulation of other biotransformation enzymes (e. g., members of the cytochrome P450 and the sulphotransferase family). In conclusion, in vitro treatment of leucocytes led to a modulated mRNA expression of selected genes, not directly related to oxidative defence systems. In vivo, however, we observed a delayed enhancement of hGSTP1, which could be associated with an initial repression of oxidative DNA damage in leucocytes from human subjects, consuming juices with high levels of polyphenols.
Hofmann
Thomas
T
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University of Jena, Jena, Germany.
Liegibel
Ute
U
Winterhalter
Peter
P
Bub
Achim
A
Rechkemmer
Gerhard
G
Pool-Zobel
Beatrice Louise
BL
D000328:Adult; D001628:Beverages / Q000032:analysis*; D002478:Cells, Cultured; D018592:Cross-Over Studies; D004249:DNA Damage / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage* / Q000032:analysis; D005638:Fruit / Q000737:chemistry*; D015870:Gene Expression; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000097:blood* / Q000235:genetics; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage* / Q000032:analysis; D059808:Polyphenols
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase