Study of antimutagenic and antioxidant activities of gallic acid and 1,2,3,4,6-pentagalloylglucose from Pistacia lentiscus. Confirmation by microarray expression profiling.
In vitro antioxidant and antimutagenic activities of two polyphenols isolated from the fruits of Pistacia lentiscus was assessed. Antioxidant activity was determined by the ability of each compound to scavenge the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH*), to inhibit xanthine oxidase and to inhibit the lipid peroxidation induced by H(2)O(2) in K562 cell line. Antimutagenic activity was assayed with SOS chromotest using Escherichia coli PQ37 as tester strain and Comet assay using K562 cell line. 1,2,3,4,6-Pentagalloylglucose was found to be more effective to scavenge DPPH* radical and protect against lipid peroxidation. Moreover, these two compounds induced an inhibitory activity against nifuroxazide and aflatoxin B1 mutagenicity. The protective effect exhibited by these molecules was also determined by analysis of gene expression as response to an oxidative stress. For this purpose, we used a cDNA-microarray containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair proteins. We found that 1,2,3,4,6-pentagalloylglucose induced a decrease in the expression of 11 transcripts related to antioxidant enzymes family (GPX1, TXN, AOE372, SHC1 and SEPW1) and DNA repair (POLD1, APEX, POLD2, MPG, PARP and XRCC5). The use of Gallic acid, induced expression of TXN, TXNRD1, AOE372, GSS (antioxidant enzymes) and LIG4, POLD2, MPG, GADD45A, PCNA, RPA2, DDIT3, HMOX2, XPA, TDG, ERCC1 and GTF2H1 (DNA repair) as well as the repression of GPX1, SEPW1, POLD1 and SHC1 gene expression.
Abdelwahed
Afef
A
Unité de Pharmacognosie/Biologie Moléculaire 99/UR/07-03, Faculté de Pharmacie/Médecine Dentaire de Monastir, Rue Avicenne, 5000 Monastir, Tunisia.
Bouhlel
Ines
I
Skandrani
Ines
I
Valenti
Kita
K
Kadri
Malika
M
Guiraud
Pascal
P
Steiman
Régine
R
Mariotte
Anne-Marie
AM
Ghedira
Kamel
K
Laporte
François
F
Dijoux-Franca
Marie-Geneviève
MG
Chekir-Ghedira
Leila
L
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D016166:Free Radical Scavengers / Q000378:metabolism; D005707:Gallic Acid / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000037:antagonists & inhibitors; D020014:K562 Cells; D015227:Lipid Peroxidation / Q000187:drug effects*; D009152:Mutagenicity Tests; D009581:Nitrofurans / Q000037:antagonists & inhibitors; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D027927:Pistacia / Q000737:chemistry*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D016587:Antimutagenic Agents; D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D047348:Hydrolyzable Tannins; D062385:Hydroxybenzoates; D009581:Nitrofurans; C435084:pentagalloylglucose; D005707:Gallic Acid; D016604:Aflatoxin B1; D014969:Xanthine Oxidase; C013150:nifuroxazide