title: Potent protection of gallic acid against DNA oxidation: results of human and animal experiments.
abstract: Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a constituent of plant derived foods, beverages and herbal remedies. We investigated its DNA protective properties in a placebo controlled human intervention trial in single cell gel electrophoresis experiments. Supplementation of drinking water with GA (12.8 mg/person/d) for three days led to a significant reduction of DNA migration attributable to oxidised pyrimidines (endonuclease III sensitive sites) and oxidised purines (formamidopyrimidine glycosylase sensitive sites) in lymphocytes of healthy individuals by 75% and 64% respectively. Also DNA damage caused by treatment of the cells with reactive oxygen species (ROS) was reduced after GA consumption (by 41%). These effects were paralleled by an increase of the activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and glutathion-S-transferase-π) and a decrease of intracellular ROS concentrations in lymphocytes, while no alterations of the total antioxidant capacity (TAC), of malondialdehyde levels in serum and of the urinary excretion of isoprostanes were found. Experiments with rats showed that GA reduces oxidatively damaged DNA in lymphocytes, liver, colon and lungs and protects these organs against γ-irradiation-induced strand breaks and formation of oxidatively damaged DNA-bases. Furthermore, the number of radiation-induced preneoplastic hepatic foci was decreased by 43% after oral administration of the phenolic. Since we did not find alterations of the TAC in plasma and lipid peroxidation of cell membranes but intracellular effects it is likely that the antioxidant properties of GA seen in vivo are not due to direct scavenging of radicals but rather to indirect mechanisms (e.g. protection against ROS via activation of transcription factors). As the amount of GA used in the intervention trial is similar to the daily intake in Middle Europe (18 mg/person/day), our findings indicate that it may contribute to prevention of formation of oxidatively damaged DNA in humans.
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Austria.
authors.forename: Franziska
authors.initials: F
authors.lastname: Ferk
authors.forename: Asima
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.forename: Julia
authors.initials: J
authors.lastname: Bichler
authors.forename: Miroslav
authors.initials: M
authors.lastname: Mišík
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wagner
authors.forename: Bettina
authors.initials: B
authors.lastname: Grasl-Kraupp
authors.forename: Sandra
authors.initials: S
authors.lastname: Sagmeister
authors.forename: Gerald
authors.initials: G
authors.lastname: Haidinger
authors.forename: Christine
authors.initials: C
authors.lastname: Hoelzl
authors.forename: Armen
authors.initials: A
authors.lastname: Nersesyan
authors.forename: Maria
authors.initials: M
authors.lastname: Dušinská
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simić
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmüller
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D005707:Gallic Acid / Q000097:blood / Q000494:pharmacology*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D005707:Gallic Acid; D004247:DNA; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat