Non-mutagenic or genotoxic effects of medicinal aqueous extracts from the Agaricus blazei mushroom in V79 cells

Agaricus blazei Murill is a mushroom largely consumed due to its medicinal properties. Effects of aqueous extract from its lineage AB97/11 in 2 fruiting body development stages (closed and opened pileus) were evaluated on chinese hamster V79 cells using cytokinesis blocking micronucleus (CBMN) and comet assays. The cells were treated at 0.15% concentration of aqueous extract prepared at different temperatures: ice-cold (4°C), room temperature (21°C) and warm (60°C). The extracts were applied in mutagenicity and antimutagenicity protocols (simultaneous, pre-incubation and continuous). The results showed that the aqueous extracts of Agaricus blazei lineage AB97/11 obtained at the 3 temperatures and both development stages did not present mutagenic or antimutagenic effect in V79 cells either in CBMN or comet assay.

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

Isoflavones are phenolic compounds widely distributed in plants and found in a high percentage in soybeans. They have important biological properties and are regarded as potential chemopreventive agents. The aim of this study was to verify the preventive effect of two soy isoflavones (genistein and daidzein) by a micronucleus assay, analysis of GST activity, and real-time RT-PCR analysis of GSTa2 gene expression. Mutagens of direct (doxorubicin) and indirect (2-aminoanthracene) DNA damage were used. Hepatoma cells (HTC) were treated with genistein or daidzein for 26 h at noncytotoxic concentrations; 10 μM when alone, and 0.1, 1.0 and 10 μM when combined with genotoxic agents. The micronucleus test demonstrated that both isoflavones alone had no genotoxic effect. Genistein showed antimutagenic effects at 10 μM with both direct and indirect DNA damage agents. On phase II enzyme regulation, the current study indicated an increase in total cytoplasmic GST activity in response to genistein and daidzein at 10 μM supplementation. However, the mRNA levels of GSTa2 isozymes were not differentially modulated by genistein or daidzein. The results point to an in vitro antimutagenic activity of genistein against direct and indirect DNA damage-induced mutagenicity. © 2012 Springer Science+Business Media B.V.

Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae)

Studies have shown that Casearia sylvestris compounds protect DNA from damage both in vitro and in vivo. Complementarily, the aim of the present study was to assess the chemopreventive effect of casearin B (CASB) against DNA damage using the Ames test, the comet assay and the DCFDA antioxidant assay. The genotoxicity was assessed by the comet assay in HepG2 cells. CASB was genotoxic at concentrations higher than 0.30μM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H2O2 in the HepG2 cell line in concentrations above 0.04μM with post-treatment, and above 0.08μM with pre-treatment. CASB was not mutagenic (Ames test) in TA 98 and TA 102. In the antimutagenicity assays, the compound was a strong inhibitor against aflatoxin B1 (AFB) in TA 98 (>88.8%), whereas it was moderate (42.7-59.4%) inhibitor against mytomicin C (MMC) in TA 102. Additionally, in the antioxidant assay using DCFDA, CASB reduced reactive oxygen species (ROS) generated by H2O2. In conclusion, CASB was genotoxic to HepG2 cells at high concentrations; was protective of DNA at low concentrations, as shown by the Ames test and comet assay; and was also antioxidant. © 2012 Elsevier Ltd.

Lentinula edodes (Shiitake) modulates chemically induced mutagenesis by enhancing pitting

This study was undertaken to understand how Lentinula edodes modulates in vivo mutagenesis induced by alkylating agents in bone marrow and peripheral blood as described in our previous article. Male Swiss mice were pretreated for 15 consecutive days with aqueous extracts prepared from L. edodes, after which, the number of circulating blood cells, normal erythroid bone marrow cell cycling, and phagocytosis of micronucleated reticulocyte (MNRET) and activation of spleen macrophages were assessed. The results indicate that the antimutagenicity seen in bone marrow and peripheral blood is exerted by distinct compounds with different actions. The antimutagenic effect in bone marrow is exerted by compounds subject to degradation at deep-freeze storage temperature of -20 C. On the other hand, compounds responsible for antimutagenicity in peripheral blood are not subject to degradation at -20 C. The results also indicate that the antimutagenic action in peripheral blood leading to the reduction of circulating MNRET occurs in the spleen primarily through a phagocytic activity due to higher macrophage numbers and probably not due to the enhanced activation state of individual cells. © Mary Ann Liebert, Inc.

Estrogenic and chemopreventive activities of xanthones and flavones of Syngonanthus (Eriocaulaceae)

The possible benefits of some bioactive flavones and xanthones present in plants of the genus Syngonanthus prompted us to screen them for estrogenic activity. However, scientific research has shown that such substances may have undesirable properties, such as mutagenicity, carcinogenicity and toxicity, which restrict their use as therapeutic agents. Hence, the aim of this study was to assess the estrogenicity and mutagenic and antimutagenic properties. We used recombinant yeast assay (RYA), with the strain BY4741 of Saccharomyces cerevisiae, and Ames test, with strains TA100, TA98, TA97a and TA102 of Salmonella typhimirium, to evaluate estrogenicity, mutagenicity and antimutagenicity of methanolic extracts of Syngonanthus dealbatus (S.d.), Syngonanthus macrolepsis (S.m.), Syngonanthus nitens (S.n.) and Syngonanthus suberosus (S.s.), and of 9 compounds isolated from them (1 = luteolin, 2 = mix of A-1,3,6-trihydroxy-2-methoxyxanthone and B-1,3,6-trihydroxy-2,5- dimethoxyxanthone, 3 = 1,5,7-trihydroxy-3,6-dimethoxyxanthone, 4 = 1,3,6,8-tetrahydroxy-2,5-dimethoxyxanthone, 5 = 1,3,6,8-tetrahydroxy-5- methoxyxanthone, 6 = 7-methoxyluteolin-8-C-β-glucopyranoside, 7 = 7-methoxyluteolin-6-C-β-glucopyranoside, 8 = 7,3′-dimethoxyluteolin- 6-C-β-glucopyranoside and 9 = 6-hydroxyluteolin). The results indicated the estrogenic potential of the S. nitens methanol extract and four of its isolated xanthones, which exhibited, respectively, 14.74 ± 1.63 nM; 19.54 ± 6.61; 7.20 ± 0.37; 6.71 ± 1.02 e 10.01 ± 4.26 nM of estradiol-equivalents (EEQ). None of the extracts or isolated compounds showed mutagenicity in any of the test strains and all of them showed antimutagenic potential, in particular preventing mutations caused by aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P). The results show that the xanthones, only isolated from the methanol extract of S. nitens capitula, probably were the responsible for its estrogenic activity and could be useful as phytoestrogens, providing a new opportunity to develop hormonal agents. In addition, flavones and xanthones could also be used as a new antimutagenic agent. Since, the mutagens are involved in the initiation and promotion of several human diseases, including cancer, the significance of novel bioactive phytocompounds in counteracting these pro-mutagenic and carcinogenic effects is now gaining credence. © 2013 Elsevier Inc. All rights reserved.

Avaliação da capacitação de quimioprevenção de Eugenia jambolana em linhagem de hepatocarcinoma celular (HepG2 e Hepa 1c1c7)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da mutagenicidade, antimutagenicidade e estrogenicidade de Byrsonima spp

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação da atividade antimutagênica de alguns produtos naturais de origem animal por meio de ensaios com células HepG2

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo do potencial antimutagênico, mutagênico, estrogênico e antibacteriano de flavonoides

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ação do licopeno na proteção contra danos induzidos no DNA in vivo e in vitro

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mecanismos de antimutagenicidade do cogumelo Agaricus brasiliensis sobre lesões no DNA induzidas in vivo e in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pre-treatment with glutamine reduces genetic damage due to cancer treatment with cisplatin

Cisplatin is an effective antineoplastic drug. However, it provokes considerable collateral effects, including genotoxic and clastogenic activity. It has been reported that a diet rich in glutamine can help inhibit such collateral effects. We evaluated this activity in 40 Swiss mice, distributed into eight experimental groups: G1 - Control group (PBS 0.1 mL/10g body weight); G2 - cisplatin group (cisplatin 6 mg/kg intraperitoneally); G3, G4, G5 - glutamine groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally); G6, G7, G8 - Pre-treatment groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally and cisplatin 6 mg/kg intraperitonially). For the micronucleus assay, samples of blood were collected (before the first use of the drugs at T0, then 24 (T1) and 48 (T2) hours after the first administration). For the comet assay, blood samples were collected only at T2. The damage reduction percentages for the micronucleus assay were 90.0, 47.3, and 37.3% at T1 and 46.0, 38.6, and 34.7% at T2, for G6, G7, and G8 groups, respectively. For the comet assay, the damage reduction percentages were 113.0, 117.4, and 115.0% for G6, G7, and G8, respectively. We conclude that glutamine is able to prevent genotoxic and clastogenic damages caused by cisplatin.

Differences in the hydroxylation pattern of flavonoids alter their chemoprotective effect against direct- and indirect-acting mutagens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of the antimutagenic activity and mode of action of the fructooligosaccharide inulin in the meristematic cells of Allium cepa culture

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mutagenic and antimutagenic effects of aqueous extract of rosemary (Rosmarinus officinalis L.) on meristematic cells of Allium cepa

Polyphenolic compounds present in rosemary were found to have antioxidant properties, anticarcinogenic activity, and to increase the detoxification of pro-carcinogens. The aim of the study was to determine the effect the aqueous extract of rosemary (AER) on mutagenicity induced by methylmethane sulfonate in meristematic cells of Allium cepa, as well as to describe its mode of action. Anti-mutagenicity experiments were carried out with 3 different concentrations of AER, which alone showed no mutagenic effects. In antimutagenicity experiments, AER showed chemopreventive activity in cultured meristematic cells of A. cepa against exposure to methylmethane sulfonate. Additionally, post-treatment and simultaneous treatment using pre-incubation protocols were the most effective. Evaluation of different protocols and the percent reduction in DNA indicated bioantimutagenic as well desmutagenic modes of action for AER. AER may be chemopreventive and antimutagenic.