ABSTRACT
Mutagenic and antimutagenic activities against direct acting mutagens, nifuroxazide (NF) and sodium azide (SA), and indirect acting mutagen aflatoxin B1 (AFB1) of extracts prepared from aerial parts of Pituranthos tortuosus were investigated in bacterial assay systems (i.e., the Ames test with Salmonella typhimurium TA100, TA98, TA1538, TA1535, and the SOS chromotest with Escherichia coli PQ 37). It was found that all extracts obtained from P. tortuosus decreased the mutagenicity induced by AFB1 (10 microg/assay), SA (1.5 microg/assay), and NF (20 microg/assay). Ethyl acetate, acetone, methanol, and total oligomer flavenoid extracts exhibited the highest inhibition level of mutagenicity induced by the indirect mutagen AFB1. In addition, antiproliferative and apoptotic properties of these extracts have also been reported using two leukemia cell lines, L1210 and K562. The results revealed that all extracts showed a significant cytotoxic effect on these cell lines, and the effect was greater in the presence of human K562 chronic myelogenous leukemia cells, whereas they do not induce apoptosis.
Subject(s)
Antimutagenic Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apiaceae , Apoptosis/drug effects , DNA, Bacterial/drug effects , Escherichia coli/drug effects , Mutagens/pharmacology , Salmonella typhimurium/drug effects , Aflatoxin B1/pharmacology , Animals , Antimutagenic Agents/chemistry , Antimutagenic Agents/toxicity , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/toxicity , Apiaceae/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Escherichia coli/genetics , Humans , Hydroxybenzoates/pharmacology , K562 Cells , Mice , Mutagens/chemistry , Mutagens/toxicity , Mutation/drug effects , Nitrofurans/pharmacology , Plant Components, Aerial , Plant Extracts/pharmacology , Salmonella typhimurium/genetics , Sodium Azide/pharmacologyABSTRACT
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.
Subject(s)
Antimutagenic Agents/pharmacology , Antioxidants/pharmacology , Enzyme Inhibitors/pharmacology , Gallic Acid/pharmacology , Hydrolyzable Tannins/pharmacology , Lipid Peroxidation/drug effects , Pistacia/chemistry , Aflatoxin B1/antagonists & inhibitors , Comet Assay , Dose-Response Relationship, Drug , Escherichia coli/genetics , Free Radical Scavengers/metabolism , Gene Expression Profiling/methods , Humans , Hydroxybenzoates/antagonists & inhibitors , K562 Cells , Mutagenicity Tests , Nitrofurans/antagonists & inhibitors , Oligonucleotide Array Sequence Analysis/methods , Xanthine Oxidase/antagonists & inhibitorsABSTRACT
This study evaluates mutagenic and antimutagenic effects of aqueous, total oligomers flavonoïds (TOF), ethyl acetate and methanol extracts from aerial parts of Cyperus rotundus with the Salmonella typhimurium assay system. The different extracts showed no mutagenicity when tested with Salmonella typhimurium strains TA98, TA100, TA1535 and TA1538 either with or without the S9 mix. On the other hand, our results showed that all extracts have antimutagenic activity against Aflatoxin B1 (AFB1) in TA100 and TA98 assay system, and against sodium azide in TA100 and TA1535 assay system. TOF, ethyl acetate and methanol extracts exhibited the highest inhibition level of the Ames response induced by the indirect mutagen AFB1. Whereas, ethyl acetate and methanol extracts exhibited the highest level of protection towards the direct mutagen, sodium azide, induced response. In addition to antimutagenic activity, these extracts showed an important free radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. TOF, ethyl acetate and methanol extracts showed IC(50) value of 15, 14 and 20µg/ml, respectively. Taken together, our finding showed that C. rotundus exhibits significant antioxidant and antimutagenic activities.
