TY - JOUR
T1 - Potent protection of gallic acid against DNA oxidation
T2 - results of human and animal experiments
AU - Ferk, Franziska
AU - Chakraborty, Asima
AU - Jäger, Walter
AU - Kundi, Michael
AU - Bichler, Julia
AU - Mišík, Miroslav
AU - Wagner, Karl-Heinz
AU - Grasl-Kraupp, Bettina
AU - Sagmeister, Sandra
AU - Haidinger, Gerald
AU - Hoelzl, Christine
AU - Nersesyan, Armen
AU - Dušinská, Maria
AU - Simić, Tatjana
AU - Knasmüller, Siegfried
N1 - 2011 Elsevier B.V. All rights reserved.
PY - 2011/10/1
Y1 - 2011/10/1
N2 - 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-pi) 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 gamma-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.
AB - 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-pi) 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 gamma-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.
KW - Animals
KW - Antioxidants
KW - DNA
KW - DNA Damage
KW - Gallic Acid
KW - Glutathione S-Transferase pi
KW - Humans
KW - Lymphocytes
KW - Oxidation-Reduction
KW - Oxidative Stress
KW - Rats
KW - Reactive Oxygen Species
U2 - 10.1016/j.mrfmmm.2011.07.010
DO - 10.1016/j.mrfmmm.2011.07.010
M3 - Article
C2 - 21827773
SN - 1386-1964
VL - 715
SP - 61
EP - 71
JO - Mutation Research: fundamental and molecular mechanisms of mutagenesis
JF - Mutation Research: fundamental and molecular mechanisms of mutagenesis
IS - 1-2
ER -
