Potent protection of gallic acid against DNA oxidation: Results of human and animal experiments
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
Volume 715, Issues 1-2, 1 October 2011, Pages 61-71
Franziska Ferka, Asima Chakrabortya, Walter Jägerb, Michael Kundic, Julia Bichlera, Miroslav Mišíka, Karl-Heinz Wagnerd, Bettina Grasl-Krauppa, Sandra Sagmeistera, Gerald Haidingere, Christine Hoelzla, Armen Nersesyana, Maria Dušinskáf, Tatjana Simića, Siegfried Knasmüllera, ,
a Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna, Austria
b Department of Clinical Pharmacy and Diagnostic, University of Vienna, Vienna, Austria
c Institute of Environmental Health, Center for Public Health, Medical University of Vienna, A-1090 Vienna, Austria
d Department of Nutritional Sciences, University of Vienna, 1090 Vienna, Austria
e Department of Epidemiology, Center for Public Health, Medical University of Vienna, A-1090 Vienna, Austria
f Health Effect Laboratory, Center for Ecological Economics, Norwegian Institute for Air Research, NO-2027 Kjeller, Norway
Received 4 February 2011; revised 23 June 2011; Accepted 22 July 2011. Available online 30 July 2011.
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.
Highlights
► Gallic acid (GA, 12 mg/P/d) prevented in a human intervention trial DNA migration caused by ROS and formation of oxidized DNA bases in lymphocytes.
► Furthermore, it increased the activities of antioxidant enzymes in plasma and decreased intracellular ROS levels.
► In rats, DNA protection against radiation-induced DNA damage was seen in various inner organs.
► Subsequent animal experiments showed that GA prevents also formation of radiation induced preneoplastic hepatic foci.
► The dose of GA we used is lower than the daily uptake of Germany via foods (18 mg/P/d).
Keywords: Gallic acid; Antioxidant; Single cell gel electrophoresis assay
doi:10.1016/j.mrfmmm.2011.07.010
---------------------
"Gallic acid (GA), a polyphenolic natural product, has the capacity to chelate free iron"
Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis.
Free Radic Biol Med. 2010 Jul 15;49(2):258-67. Epub 2010 Apr 18.
Pal C, Bindu S, Dey S, Alam A, Goyal M, Iqbal MS, Maity P, Adhikari SS, Bandyopadhyay U.
Department of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.
Abstract
Nonsteroidal anti-inflammatory drug (NSAID)-induced oxidative stress plays a critical role in gastric mucosal cell apoptosis and gastropathy.
NSAIDs induce the generation of hydroxyl radical ((*)OH) through the release of free iron, which plays an important role in developing gastropathy.
Thus, molecules having both iron-chelating and antiapoptotic properties will be beneficial in preventing NSAID-induced gastropathy.
Gallic acid (GA), a polyphenolic natural product, has the capacity to chelate free iron.
Here, we report that GA significantly prevents, as well as heals, NSAID-induced gastropathy.
In vivo, GA blocks NSAID-mediated mitochondrial oxidative stress by preventing mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion.
In vitro, GA scavenges free radicals and blocks (*)OH-mediated oxidative damage.
GA also attenuates gastric mucosal cell apoptosis in vivo as well as in vitro in cultured gastric mucosal cells as evident from the TUNEL assay.
GA prevents NSAID-induced activation of caspase-9, a marker for the mitochondrial pathway of apoptosis, and restores NSAID-mediated collapse of the mitochondrial transmembrane potential and dehydrogenase activity.
Thus, the inhibition of mitochondrial oxidative stress by GA is associated with the inhibition of NSAID-induced mitochondrial dysfunction and activation of apoptosis in gastric mucosal cells, which are responsible for gastric injury or gastropathy.
Copyright 2010 Elsevier Inc. All rights reserved.
PMID:20406680
-----------------