Bio-antimutagenic Effect Research Articles

Antioxidant, photoprotective and antimutagenic properties of Phyllanthus spp. from Cuban flora

Context: Sunlight ultraviolet (UV) radiation constitutes a significant physical carcinogen in nature. It could induce direct and indirect DNA damage, which if not properly repaired may generate mutations. Plants in the genus Phyllanthus (Phyllanthaceae) are widely used in traditional medicine and known as natural sources of antioxidant compounds. Recent investigations support their genoprotective activity against chemical and physical mutagens, among them UV radiation. Aims: To compare the antioxidant, photoprotective and antimutagenic activity of aqueous extracts obtained from three Cuban endemic Phyllanthus species: P. chamaecristoides Urb., P. microdictyus Urb., and P. williamioides Gr. Methods: DPPH radical scavenging assay was use for quantify the in vitro antioxidant capacity. Genoprotection against UVC radiation was measured at two levels: structural DNA damage and mutations, by means of the SOS Chromotest, Survival assay, and RifR mutagenicity test in Caulobacter crescentus cells. Results: P. chamaecristoides extract showed the highest antioxidant capacity (IC50 = 0.032 mg/mL), and together with P. microdictyus exhibited the greatest bioantimutagenic effects (RMF ≤ 5%), diminishing UVC-induced DNA damage in three and five times, respectively. Conclusions: The reduction in DNA damage is not founded in a Phyllanthus aqueous extracts desmutagenic effect. It is possible that the genoprotective activity detected could be due to modulation of DNA repair mechanisms, diminishing SOS response and related mutagenicity induced by UVC radiation. Moreover, high antioxidant capacity could also decrease UV radiation oxidative-damage. Altogether, these outcomes validate future pre-clinic research regarding Phyllanthus photoprotective capacities.

Antimutagenic potential of chickrassy (Chukrasia tabularis A. Juss.) bark

The present study aims to assess the antimutagenic potential of methanol extract and different fractions (hexane, ethyl acetate and butanol) of chickrassy (Chukrasia tabularis), belonging to family meliaceae by employing histidine point reversion assay. The antimutagenic effect was evaluated against mutagens, 4-Nitro-o-phenylenediamine and sodium azide and promutagen, 2-Aminofluorene of TA98 and TA100 strain of Salmonella typhimurium. The co-incubation and pre-incubation mode of treatments were used to evaluate the bioantimutagenic and desmutagenic effects, respectively. From the results obtained, it was clear that methanol extract and its fractions showed more desmutagenic effect than bioantimutagenic effect. The methanol extract was found to be most active in TA98 while ethyl acetate fraction showed good results in TA100 strain against both promutagen and direct acting mutagen. High performance liquid chromatography (HPLC) analysis of methanol extract was carried out for the identification of chemical constituents and the results revealed that catechin, quercetin and rutin have contributed to its antimutagenic activity. Key words: Chickrassy, bioantimutagen, desmutagen, Salmonella typhimurium, high performance liquid chromatography (HPLC).

An investigation of antigenotoxic properties of plant extracts of Chelidonium majus L., Plantago major L. and Tussilago farfara L.

The antigenotoxic properties of the sap from three medicinal plants, the greater celandine (Chelidonium majus L.), the greater plantain (Plantago major L.), and coltsfoot (Tussilago farfara L.), were studied using two bacterial test systems (SOS chromotest and Rec assay). It was determined using the combined effect of the plant sap and model genotoxicants on the cells of test strains that the plant sap of the greater celandine reveals a dismutagenic effect decreasing the genotoxic effect of nalidixic acid in the SOS chromotest and furacilin in the Rec assay. The plants sap of the greater celandine and coltsfoot (in 1: 10 and 1: 100 dilutions) demonstrated a bioantimutagenic effect in the SOS chromotest because pre-incubation of the E. coli PQ37 cells test strain with the sap of these plants resulted in a significant decrease of the genotoxic effect of nalidixic acid. The antigenotoxic effect of the greater plantain sap was not statistically significant in both test systems. Possible mechanisms of determining the antigenotoxic properties of the plant sap from greater celandine and coltsfoot are discussed.

Antioxidant and Antimutagenic Activities of Randia echinocarpa Fruit

We report for the first time the antioxidant and antimutagenic activities of fractions from Randia echinocarpa fruit, which is a Rubiaceae plant native to Sinaloa, Mexico. This fruit has been traditionally used in the prevention or treatment of cancer, among other diseases. The pulp of the fruit was sequentially extracted with solvents of different polarity (i.e. hexane, chloroform, methanol and water). A high extraction yield was obtained with methanol (72.17% d.w.). The aqueous extract showed the highest content of phenolics (2.27 mg/g as ferulic acid equivalents) and the highest antioxidant activity based on the beta-carotene bleaching method (486.15). The commercial antioxidant BHT was used as control (835.05). Antimutagenic activity of the aqueous extract (0-500 microg/tube) was evaluated using the Salmonella microsuspension assay (YG1024 strain) and 1-NP as the mutagen (50 and 100 ng/tube). The aqueous extract was neither toxic nor mutagenic and the percentage of inhibition on 1-NP mutagenicity was 32 and 53% at doses of 50 and 100 ng/tube, respectively. The results of the double incubation assay suggest that the extract inhibited the mutagenicity of 1-NP by a combination of desmutagenic and bioantimutagenic effects.

Possible Mechanisms of Antimutagenicity in Fermented Soymilk Prepared with a Coculture of Streptococcus infantis and Bifidobacterium infantis

The possible mechanisms of antimutagenicity against 4-nitroquinoline-N-oxide (4-NQO; a direct mutagen) and 3,2′-dimethyl-4-amino-biphenyl (DMAB; an indirect mutagen) were examined in fermented soymilk prepared with a coculture of Streptococcus thermophilus and Bifidobacterium infantis. The antimutagenicity in the fermented soymilk was not due to the bioantimutagenic effect of modulation of DNA repair processes. The mutagenicity of DMAB decreased with increased pre-incubation of fermented soymilk and the DMAB metabolite but not with intact DMAB or an S9 mixture. Mutagenicity of 4-NQO was not affected by preincubation of fermented soymilk with this mutagen. Mutagenicity of both 4-NQO and DMAB was reduced when Salmonella Typhimurium TA 100 was pretreated with fermented soymilk, indicating that fermented soymilk affected the function of the bacterial cell, which might also lead to reduced mutagenicity of the tested mutagens. Desmutagenic and blocking effects were the main mechanisms of antimutagenicity in the fermented soymilk against DMBA. In contrast, the antimutagenic effect of the fermented soymilk on 4-NQO was primarily due to a blocking effect.

Antimutagenic activity of plant extracts. II. Bioantimutagenic effect of various fractions of cultivated sage ( Salvia officinalis L.)

Antimutagenic activity of plant extracts. II. Bioantimutagenic effect of various fractions of cultivated sage ( Salvia officinalis L.)

Bio-antimutagenic effect of S-methyl methane thiosulfonate separated from the vegetable homogenates of Cruciferae Brassica and Liliaceae Allium species

Bio-antimutagenic effect of S-methyl methane thiosulfonate separated from the vegetable homogenates of Cruciferae Brassica and Liliaceae Allium species

The Effect of Bio-antimutagens on Chlorambucil and Methotrexate Using the Wing Spot Test in Drosophila melanogaster.

When certain mutagenic anti-cancer medicines are used for cancer therapy, secondary production of cancer by the medicines themselves is feared. Certain bio-antimutagenic substances may decrease secondary cancer induction without interfering with the effectiveness of the anti-cancer therapies. The bio-antimutagenic effects of cobaltous chloride, gallic acid, taurine and isethionate on the anti-cancer medicines chlorambucil and methotrexate were investigated using the Drosophila melanogaster wing spot test. Cobaltous chloride reduced the mutagenicity of methotrexate, but not chlorambucil. Gallic acid reduced the mutagenicity of both medicines. Taurine and isethionate also reduced the mutagenicity of methotrexate.

Antimutagenicity of a partially fractionated Maillard reaction product

The Maillard reaction product was prepared by refluxing glucose (0·5 m) and tryptophan (0·5 m) at pH 11·0 and 100°C for 10 h. It was further fractionated into different molecular weights (MW) below 1000, MW 1000–5000, MW 5000–10 000, MW 10 000–30 000, MW 30 000–50 000 and MW above 50 000, by means of membrane filters. The characteristics and antimutagenicity of each glucose-tryptophan (GT) fraction were investigated. The trends of browning, reducing power, antioxidative activity and antimutagenicity of each GT fraction were generally of the order of MW above 5000 > unfractionated > MW below 1000. The antimutagenicity of each GT fraction exhibited a suitable correlation with these characteristics. The reducing power and antioxidative activity of each GT fraction could be concluded to play an important role in terms of its antimutagenicity. Additionally, an inhibitory mechanism of GT was due to a desmutagenic effect but not a bio-antimutagenic effect.

Antimutagenic Effect of Maillard Reaction Products Prepared from Glucose and Tryptophan

The antimutagenicity of Maillard reaction products (MRPs) prepared by refluxing D-glucose and L-tryptophan under various reaction conditions was determined by means of the Ames test. The dose of MRPs with 5 mg per plate showed no toxicity, and mutagenicity to Salmonella typhimurium TA98 and TA100 was used for antimutagenic assay. The mutagenicity of 2-amino-3-methylimidazo (4,5-f) quinoline (IQ) and 2-amino-6-methyldipyrido (1,2-a:3′,2′-d) imidazole (Glu-P-1) toward TA98 was markedly reduced by the addition of glucose-tryptophan MRPs, whereas the mutagenicity of 4-nitroquinoline-N-oxide (NQNO) was not inhibited. The mutagenicity of IQ, Glu-P-1, and NQNO toward TA100 was also markedly reduced by glucose-tryptophan MRPs, but the mutagenicity of NQNO was only slightly inhibited. Greater antimutagenic effects of glucose-tryptophan MRPs were found when these materials were prepared at an alkaline pH. The optimum combinations of reaction conditions for obtaining antimutagenic MRPs to IQ were glucose-tryptophan molar ratio = 0.5:0.25 at pH 9.0 for 5 and 10 h, molar ratio = 0.5:0.5 at pH 11.0 for 10 h, and molar ratio = 1.0:0.25 at pH 7.0 for 15 h and at pH 11.0 for 15 h. The antimutagenic effect of glucose-tryptophan MRPs to IQ and Glu-P-1 was well correlated with their browning intensity, reducing power, and antioxidative activity. The antimutagenicity of glucose-tryptophan MRPs might be due to both desmutagenic and bio-antimutagenic effects.

Bio-antimutagenic activities of vitamin B 6 in E. coli and mouse peripheral blood cells

Pyridoxal (PL) and pyridoxal 5′-phosphate (PLP) showed a marked bio-antimutagenic effect on UV-induced mutagenesis in E. coli B/r WP2, but not in the DNA excision repair-deficient strain WP2s uvrA under the condition where no cellular toxicity was observed. No delay in the first cell division was seen on post-treatment with PL after UV irradiation. PL reduced not only UV- but 4-nitroquinoline-1-oxide-induced mutation, while it was ineffective in N-methyl- N′-nitro- N-nitrosoguanidine- or γ-ray-treated cells. These results suggest that PL promotes DNA excision repair directly or indirectly and the decrease in the amount of unrepaired DNA damage might cause the reduction of UV-induced mutations in E. coli B/r WP2. In addition to the above observation, PLP reduced the frequency of mitomycin C- (2 mg/kg, i.p.) induced micronuclei in mouse peripheral blood cells. Simultaneous or subsequent oral administration of PLP (25 mg/kg) decreased the frequency of micronucleated peripheral reticulocytes.

Inhibitory action of peony root extract on the mutagenicity of benzo[ a]pyrene

The inhibitory effects of peony root extract on the mutagenicity of benzo[ a]pyrene (B[a]p) have been investigated in the Salmonella typhimurium reversion test. Four kinds of experiments were performed: direct chemical reaction (1) between peony root extract and B[a]p, and (2) between peony root extract and active metabolite(s) of B[a]p, (3) inhibition of metabolic processes of B[a]p with S9 mix, and (4) inhibition of activation on mutagenicity. Peony root extract interfered with the action of enzymes in the S9 mix, and inactivated the activity of B[a]p metabolites. The bio-antimutagenic effect was assayed by reversion in Salmonella typhimurium TA98 and TA100.

Effects of constituents of paeony root on the mutagenicity of benzo (a) pyrene.

Ethyl acetate, n-butanol and water extracts were prepared from a hot-water extract of Paeony root, which shows strong antimutagenic activity for benzo [α] pyrene (B [α] p). Among them, ethyl acetate and n-butanol extracts showed the antimutagenicity. The ethyl acetate extract was fractionated to 20 fractions (Fr.1-20) with Sephadex LH-20, and the n-butanol extract to 6 fractions (Fr.21-26) with preparative high performance liquid chromatography (HPLC). Antimutagenic activity was observed in Fr.2, Fr.9-12, and Fr.22. Gallic acid (GA) was found in Fr.2 and Fr.22, and pentagalloyl glucose (PGG) in Fr.9-12. The amounts of GA and PGG in Paeony root extract were determined by HPLC, and the antimutagenic activity of these extracts were attributable to GA and PGG. Antimutagenic effects of GA and PGG were explored in the following points. They are (I) reaction and adsorption of B [α] p with GA and PGG, (II) inhibition of the enzymatic activity of S9mix by GA and PGG, (III) inactivation of the metabolites of B [α] p by GA and PGG, and (IV) bio-antimutagenic effect of GA and PGG on DNA damaged bacteria. GA and PGG inactivated the metabolites of B [α] p, and PGG inhibited the enzymatic action of S9mix. Their inhibitory effect was recognized as desmutagenic action.

Antimutagenic effects of benzaldehyde and its derivatives on mutagenesis induced by 4-nitroquinoline 1-oxide in Escherichia coli.

The bio-antimutagenic potential of benzaldehyde and its derivatives was investigated on mutagenesis induced by 4-nitroquinoline 1-oxide (4NQO) in Escherichia coli WP2s uvrA trpE. Benzaldehyde and 18 kinds of hydroxy-, methoxy-, or ethoxybenzaldehydes other than 3, 4-diethoxybenzaldehyde decreased the induced mutation frequency by 42 to 91%. Among these compounds, strong bio-antimutagenic effects were observed for vanillin (3-methoxy-4-hydroxybenzaldehyde), vanillal (3-ethoxy-4-hydroxybenzaldehyde), protocatechualdehyde (3, 4-dihydroxybenzaldehyde), 2, 5-dimethoxybenzaldehyde, o-anisaldehyde (o-methoxybenzaldehyde), and m-anisaldehyde. On the other hand, benzyl alcohol or benzoic acid analogues such as vanillyl alcohol, vanillic acid, isovanillic acid, and veratric acid did not show any bio-antimutagenic effects. These observations suggest that the aldehyde radical is important for bio-antimu'tagenic activity.

Bio-antimutagenic effect of l-cysteine on diiodohydroxyquinoline-induced micronuclei in Swiss mice

The mutagenic potential of diiodohydroxyquinoline (DIHQ), a common anti-amebic drug, was tested using the in vivo micronucleus test in Swiss mice following oral administration. It was found to be mutagenic in a dose-dependent manner. Using the same model system, the bio-antimutagenic effect of the sulfhydryl compound l-cysteine against DIHQ was established.

Bio-antimutagenic effects of sesquiterpene lactones from costus root oil.

(1987). Bio-antimutagenic Effects of Sesquiterpene Lactones from Costus Root Oil. Agricultural and Biological Chemistry: Vol. 51, No. 2, pp. 585-587.

Bio-antimutagenic effect of L-ethionine on the spontaneous mutagenesis in Salmonella and Bacillus subtilis.

L-ethionine, a hepatocarcinogen, exhibited a strong bio-antimutagenic effect against spontaneous mutation in Ames' Salmonella strains as well as in a Bacillus subtilis mutator strain whose mutator activity was due to an error-prone DNA replicating enzyme. The bio-antimutagenic effect of L-ethionine was completely abolished by the presence of L-methionine, but not by D-methionine, suggesting that genetic effect of L-ethionine was expressed through its interaction with L-methionine metabolism in the treated cells.

Bio-antimutagenic effect of lactones on chemical mutagenesis in Escherichia coli.

Bio-antimutagenic effect of lactones on chemical mutagenesis in Escherichia coli.

Bio-antimutagenic effects of tannic acid on UV and chemically induced mutagenesis in Escherichia coli B/r

Tannic acid suppressed the mutagenesis in E. coli B/r WP2 trp − induced by UV or 4-nitroquinoline 1-oxide (4NQO), but not that induced by γ-rays or N-methyl- N′-nitro- N-nitrosoguanidine (MNNG). The depression of mutations induced by UV was most remarkable in the DNA-repair-proficient strain (WP2). Tannic acid, however, showed no bio-antimutagenic effect in the excision repair-deficient strain (WP2 s uvrA − or ZA159 uvrB −) under the test conditions where no cellular toxicity was observed. The effect ceased within 30 min after UV irradiation. The inhibition of the expression of Trp + phenotype and the delay of the first cell division after UV irradiation were not observed in the presence of tannic acid. From these results we conclude that tannic acid may enhance the excision-repair system probably by activating the repair enzymes or by interacting with DNA.