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1.
J Toxicol Environ Health A ; 85(9): 353-363, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34875975

RESUMO

Pedunculagin (PD), an ellagitannin found in different plant species, possesses several pharmaceutical properties, including antitumor, antioxidant, gastroprotective, hepatoprotective, and anti-inflammatory properties. However, the effects of PD alone on DNA remain to be determined. The aim of this study was to investigate the potential cytotoxic, genotoxic, and antigenotoxic activities of PD isolated from Plinia cauliflora seeds using in silico and in vitro assays. To elucidate the biological activities of PD, in silico tools indicative of antioxidant, antineoplastic, and chemopreventive activities of PD were used. Subsequently, the mutagenic/antimutagenic effects of PD were later assessed using bacteria with the Ames test, and the cytotoxic, genotoxic, and antigenotoxic effects utilizing human lymphocytes as evidenced by trypan blue exclusion test and CometChip assay. In silico analysis indicated potential antioxidant, chemopreventive, free radical scavenger, and cytostatic activities of PD. In the Ames test, PD was found to be not mutagenic; however, this plant component protected DNA against damage-mediated by mutagens 4-nitroquinoline-1-oxide and sodium azide. Regarding human lymphocytes, PD alone was cytotoxic and genotoxic; however, it also reduced DNA damage induced by doxorubicin at co- and post-treatment. In conclusion, PD showed genotoxic, antigenotoxic and cytotoxic effects in human lymphocytes and antimutagenic effects in bacteria.


Assuntos
Antimutagênicos , Antineoplásicos , Myrtaceae , Antimutagênicos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Dano ao DNA , Humanos , Linfócitos , Mutagênicos/toxicidade , Extratos Vegetais/farmacologia , Salmonella typhimurium , Sementes , Taninos
2.
Drug Chem Toxicol ; 45(2): 641-650, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32321321

RESUMO

Orthosiphon stamineus (O.S) is widely consumed for its medidcinal value including anti-inflammatory, anti-infective, and diuretic properties. The present study evaluates the cytoprotective, anti-mutagenic, and anticlastogenic efficacies of standardized extract of Orthosiphon stamineus. Normal liver cell line (WRL68) exposed to hydrogen peroxide and serum-deprived media as insults to evaluate cytoprotective and glutathione activation activities of (Et. O. s). Salmonella typhimurium TA98 and TA100 exposed to different concentrations of (Et. O. s). The influence of Et. O. s on mitotic, replicative indices as well as chromosomal aberration (CA) and sister chromatid exchange (SCE) induced in human peripheral blood lymphocytes by mitomycin C (MMC). The Et. O.s proved to be a potent scavenger for hydrogen peroxide and other free radicals in serum-depraved media, which showed to stimulate glutathione production in liver cells line. Moreover, it did not induce mutations in S. typhimurium subspecies TA98 and TA100. The standardized extract exhibited powerful antimutagenic activities as verified against both 2-nitrofluorene and sodium azide in S. typhimurium TA98 and TA100 cells, respectively. Cytogenetic tests showed high concentrations of Et. O. s to reduce the values of mitotic and replicative indices without any accompanying side effects, such as chromosomal abnormalities or SCE. To ameliorate MMC effects, pretreatment with the extract proofed to be efficient protocol. These data suggests that O. stamineus extract could be useful as cytoprotective, antimutagenic, and anticlastogenic efficacies, which owes to its potent chemoprevention, antioxidant, and glutathione activation properties.


Assuntos
Antimutagênicos , Orthosiphon , Antimutagênicos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Etanol/toxicidade , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta
3.
Drug Chem Toxicol ; 45(2): 515-522, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063063

RESUMO

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (n = 6), melanoma + vehicle (n = 10), PBS + melatonin (n = 6), and melanoma + melatonin (n = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells.


Assuntos
Antimutagênicos , Melanoma , Melatonina , Animais , Antimutagênicos/farmacologia , Ensaio Cometa , Dano ao DNA , Suplementos Nutricionais , Masculino , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL
4.
J Toxicol Environ Health A ; 85(8): 336-352, 2022 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-34903147

RESUMO

Medicinal plants have always been used for therapeutic purposes; however, some plants may contain toxic and mutagenic substances. The aim of this study was to assess the cytotoxic, genotoxic, mutagenic, antioxidant, antigenotoxic, and antimutagenic effects of the bark ethanolic extract of Spondias purpurea L. using male and female Swiss albino mice. To determine the protective effects of the extract, benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) were selected as cell damage inducers. The extract was examined at doses of 500, 1000, or 1500 mg/kg body weight (BW)via gavage alone or concomitant with B[a]P or CP. Oxidative stress was measured by quantification of blood catalase activity (CAT), reduced glutathione (GSH) levels in total blood, liver, and kidney, and concentrations of malondiadehyde (MDA) in liver and kidney. Genotoxicity and antigenotoxicity were evaluated by the comet assay using peripheral blood. Cytotoxicity, mutagenicity, and antimutagenicity were determined utilizing the micronucleus test in bone marrow and peripheral blood. The S. purpurea L extract increased CAT activity and GSH levels accompanied by a decrease in MDA levels after treatment with B[a]P and CP. No genotoxic, cytotoxic, or mutagenic effects were found in mice exposed only to the extract. These results indicate that the extract of S. purpurea exhibited protective effects against oxidative and DNA damage induced by B[a]P and CP.


Assuntos
Anacardiaceae , Antimutagênicos , Animais , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Ciclofosfamida/toxicidade , Dano ao DNA , Feminino , Masculino , Camundongos , Testes para Micronúcleos , Mutagênicos/toxicidade , Casca de Planta , Extratos Vegetais/farmacologia
5.
Bull Exp Biol Med ; 172(2): 143-145, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34853971

RESUMO

On a culture of human peripheral blood lymphocytes, antimutagenic activity of a composition from extracts of green tea leaves and Caucasian persimmon fruits was established with a modification of the mutation process induced by chemical compounds producing an alkylating effect (nitrosomethylurea and sodium fluoride). A concentration dependence of the antimutagenic efficiency of the studied phytocomposite was shown. The highest antimutagenic efficiency was observed when a combination of green tea extract at a concentration of 0.01 µg/ml and persimmon fruit extract at a concentration of 0.001 µg/ml were used. Moreover, this combination was most effective against mutations induced by both nitrosomethylurea and sodium fluoride: the antimutagen efficiency factor was 0.53 and 0.55, respectively.


Assuntos
Antimutagênicos/farmacologia , Diospyros/química , Extratos Vegetais/farmacologia , Chá/química , Adulto , Antioxidantes/farmacologia , Células Cultivadas , Análise Citogenética , Frutas/química , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Masculino , Testes de Mutagenicidade , Folhas de Planta/química , Adulto Jovem
6.
J Cancer Res Ther ; 17(6): 1339-1346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916363

RESUMO

AIMS: The aim was to compare the anticancer and antimutagenic potency of Polyalthia cerasoides seeds and stem bark. AIM OF THE STUDY: The aim of this study was to investigate the antiproliferative, apoptotic, antioxidation to DNA, and antimutagenic activity of alcoholic (PS-1 and PS-3) and petroleum ether (PS-2 and PS-4) stem bark and seed fractions of P. cerasoides. METHODS: P. cerasoides stem bark and seeds were extracted with ethanol: water mixture (9:1 ratio v: v) and fractionated with petroleum ether. Fractions were investigated for antiproliferative effect using cell by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a tetrazole assay (cell line used liver [HepG2] and cervical [HeLa] cancer cell lines), DNA damage protection using hydroxyl radical and antimutagenic effect using chromosome aberration test. RESULTS: PS-1 (IC50 10 µg/ml) and PS-3 (IC50 11 µg/ml) showed maximum antiproliferative activity against HepG2 cell lines, whereas, PS-1 (IC50 10 µg/ml), PS-2 (IC50 24 µg/ml), and PS-3 (IC50 11 µg/ml) showed better antiproliferative activity against HeLa cell lines. PS-3 and PS-4 were protective against oxidation to the supercoiled DNA molecule. Further, petroleum ether extract of both seed (PS-2) and stem bark (PS-4) showed good antimutagenicity as revealed by the less chromosomal aberrations compared to PS-1 and PS-3 fractions. CONCLUSIONS: This study demonstrated the beneficial effect of fractions against oxidation of DNA, antiproliferative, apoptotic, and antimutagenic activity. Probably, this property would be attributable by their phenolic and steroid constituents. Therefore, this plant could be used as a potential source of nutraceutical agents.


Assuntos
Antimutagênicos/farmacologia , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Casca de Planta/química , Extratos Vegetais/farmacologia , Polyalthia/química , Sementes/química , Animais , Apoptose , Proliferação de Células , Etanol/química , Células HeLa , Células Hep G2 , Humanos , Camundongos , Neoplasias/patologia
7.
Molecules ; 26(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34641463

RESUMO

The fruit and pericarp of Zanthoxylum schinifolium (ZS) have been used in traditional medicine; however, few studies have characterized ZS fruit and pericarp. Therefore, in the present study, we evaluated the safety of ZS fruit (ZSF) and pericarp (ZSP) extracts and compared their bioactivity. To evaluate the safety of ZSF and ZSP, mutagenicity, cytotoxicity, and oxidative stress assays were performed and nontoxic concentration ranges were obtained. ZSP was found to be superior to ZSF in terms of its antimutagenic, antioxidant, and anti-inflammatory activities. In the S9 mix, the mutation inhibition rate of ZSP was close to 100% at concentrations exceeding 625 µg·plate-1 for both the TA98 and TA100 strains. ZSP exhibited efficient DPPH (IC50 = 75.6 ± 6.1 µg·mL-1) and ABTS (IC50 = 57.4 ± 6 µg·mL-1) scavenging activities. ZSP inhibited the release of cytokines, involved in IL-1ß (IC50 = 134.4 ± 7.8), IL-6 (IC50 = 262.8 ± 11.2), and TNF-α (IC50 = 223.8 ± 5.8). These results indicate that ZSP contains a higher amount of biochemicals than ZSF, or that ZSP contains unique biochemicals. In conclusion, for certain physiological activities, the use of ZSP alone may be more beneficial than the combined use of ZSF and ZSP.


Assuntos
Anti-Inflamatórios/farmacologia , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Etanol/química , Frutas/química , Extratos Vegetais/farmacologia , Zanthoxylum/química , Citocinas/metabolismo , Sequestradores de Radicais Livres/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Salmonella typhimurium/efeitos dos fármacos
8.
Pak J Pharm Sci ; 34(3): 987-993, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602423

RESUMO

The current study investigated the prospective effect of Silybum marianum L. and Eucalyptus camaldulensis Dehnh extracts against skin cancer. Skin cancer was induced by 7,12-dimethylbenz(a) anthracene (DMBA) in young Balb/c mice. Plant extracts were administered to animals orally, once/day (100mg/kg, 5 days/week) for the 20 weeks. Anticancer activity was examined via tumor progression, where antimutagenic activity was measured using 8-OHdG and sister chromatid exchange (SCE) levels. Eucalyptus camaldulensis Dehnh. leaves extract and Silybum marianum L. leaves extract significantly reduced 8-OHdG in cultured human lymphocytes in a dose-response manner (P<0.05). Similarly, the leave extracts of both plants significantly reduced chromosomal damage as measured by SCE levels (P<0.05). In the skin painting assay, the leave extracts of both plants significantly delayed the onset of tumors compared to DMBA treated group (P<0.05). The Silybum marianum leaves extract significantly reduced tumor incidence (P<0.01) and papilloma frequency (P<0.01) induced by DMBA. The Eucalyptus camaldulensis leaves extract significantly reduced the number of tumors per animal (P<0.05) and incidence of tumors (P<0.001). The in vitro and in vivo findings showed that leaves of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. extracts might be a promising source for anticancer and antimutagenic agents against human cancer.


Assuntos
Antimutagênicos/farmacologia , Carcinoma/induzido quimicamente , Eucalyptus , Cardo-Mariano , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias Cutâneas/induzido quimicamente , Pele/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Carcinógenos/toxicidade , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Técnicas In Vitro , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Folhas de Planta , Pele/metabolismo , Pele/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Carga Tumoral/efeitos dos fármacos
9.
J Biochem Mol Toxicol ; 35(12): e22917, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34541749

RESUMO

Phytochemicals have been suggested as an effective strategy for cancer prevention. Within this context, triterpene betulinic acid (BA) exhibits several biological properties but its chemopreventive effect has not been fully demonstrated. The present study investigated the antigenotoxic potential of BA against doxorubicin (DXR)-induced genotoxicity using the mouse peripheral blood micronucleus assay, as well as its anticarcinogenic activity against 1,2dimethylhydrazine (DMH)-induced colorectal lesions in rats. Micronuclei (MN) assay and aberrant crypt foci assay were used to assess the antigenotoxic and the anticarcinogenic potential, respectively. The molecular mechanisms underlying the anticarcinogenic activity of BA were evaluated by assessing anti-inflammatory (COX-2) and antiproliferative (PCNA) pathways. The results demonstrated that BA at the dose of 0.5 mg/kg bodyweight exerted antigenotoxic effects against DXR, with a reduction of 70.2% in the frequencies of chromosomal damage. Animals treated with BA showed a 64% reduction in the number of preneoplastic lesions when compared to those treated with the carcinogen alone. The levels of COX-2 and PCNA expression in the colon were significantly lower in animals treated with BA and DMH compared to those treated with the carcinogen alone. The chemopreventive effect of BA is related, at least in part, to its antiproliferative and anti-inflammatory activity, indicating a promising potential of this triterpene in anticancer therapies, especially for colorectal cancer.


Assuntos
Anticarcinógenos/farmacologia , Antimutagênicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/prevenção & controle , Ciclo-Oxigenase 2/metabolismo , Doxorrubicina/toxicidade , Inflamação/prevenção & controle , Masculino , Camundongos , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/prevenção & controle , Transdução de Sinais/efeitos dos fármacos
10.
Artigo em Inglês | MEDLINE | ID: mdl-34583820

RESUMO

Pullulan is a biocompatible and water-soluble exo-polysaccharide produced by primary strains of the fungus Aureobasidium pullulans. It is frequently used in the pharmaceutical and food industries. In this study, possible cytotoxic effect of pullulan was assessed using the MTT assay in the human breast cancer (MCF-7) cell line. Micronucleus (MN), micronucleus-FISH (MN-FISH), random amplified polymorphic DNA (RAPD-PCR), and comet assays were used to investigate genotoxic and antigenotoxic effects of pullulan against mitomycin C (MMC) (at MN assay) and hydrogen peroxide (at comet assay) in human lymphocytes. Antigenotoxicity was determined using two different applications: 1 h pretreatment and simultaneous treatment. In the MTT assay, pullulan significantly reduced the cell viability at 15.6-2000 µg/mL compared to the control. No significant alterations in MN rates were found in human lymphocytes treated with different concentrations of pullulan compared to the control. In contrast, co-treatment of pullulan and MMC decreased the frequency of MN in almost all the treatment concentrations and durations compared to the MMC. No significant change was observed in the frequency of the centromere-positive C + or negative C- MNi compared to the positive control. In comet assay, pullulan did not affect comet tail intensity compared to the negative control. On the contrary, pullulan in combination with H2O2 significantly decreased tail intensity at almost all the concentrations compared to the positive control. The changes occurring in RAPD-PCR profiles following pullulan treatments included an increase or decrease in band intensity and gain or loss of bands. These results indicate that exopolysaccharide Pullulan is not genotoxic; moreover, it possesses a protective effect against MMC and H2O2 induced genotoxicity. In breast cancer cells, pullulan induced cytotoxic/anti-proliferative effect.


Assuntos
Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Glucanos/farmacologia , Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Adolescente , Adulto , Ensaio Cometa , Feminino , Humanos , Hibridização in Situ Fluorescente , Células MCF-7 , Masculino , Testes para Micronúcleos , Mitomicina/antagonistas & inibidores , Adulto Jovem
11.
Molecules ; 26(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34500813

RESUMO

Aromatic halophytes represent an exceptional source of natural bioactive compounds for the food industry. Crithmum maritimum L., also known as sea fennel, is a halophyte plant colonizing cliffs and coastal dunes along Mediterranean and Atlantic coasts. It is well known to produce essential oils and polyphenols endowed with antioxidant and biological effects. The present work reports the phytochemical profile, as well as antioxidant, antimicrobial and antimutagenic properties of C. maritimum leaf hydro-alcoholic extract. From LC-ESI-MS analysis, eighteen phenolic compounds were depicted in sea fennel extract and the amount of total phenolic content exceeds 3% DW. Accordingly, C. maritimum extract showed strong antioxidant activities, as evidenced by in vitro (DPPH, ORAC, FRAP) and ex vivo (CAA-RBC and hemolysis) assays. An important antimicrobial activity against pathogenic strains was found as well as a strong capacity to inhibit Staphylococcus aureus (ATCC 35556) biofilm formation. Sea fennel extracts showed a significant decrease of mutagenesis induced by hydrogen peroxide (H2O2) and menadione (ME) in Saccharomyces cerevisiae D7 strain. In conclusion, our results show that C. maritimum is an exceptional source of bioactive components and exert beneficial effects against oxidative or mutagenic mechanisms, and pathogenic bacteria, making it a potential functional food.


Assuntos
Suplementos Nutricionais , Magnoliopsida/química , Extratos Vegetais/química , Plantas Comestíveis/química , Antibacterianos/química , Antibacterianos/farmacologia , Antimutagênicos/química , Antimutagênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas Tolerantes a Sal/química , Staphylococcus aureus/efeitos dos fármacos
12.
Chem Biodivers ; 18(10): e2000936, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34432933

RESUMO

The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography-mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC2 . The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin.


Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Nigella damascena/química , Nigella sativa/química , Óleos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Aflatoxina B1/antagonistas & inibidores , Antimutagênicos/química , Antimutagênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Picratos/antagonistas & inibidores , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Salmonella typhimurium/química
13.
Food Chem Toxicol ; 154: 112319, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34087405

RESUMO

Previously, we isolated and identified anti-mutagenic and anti-inflammatory components from Vitis coignetiae (crimson glory vine, known as yamabudo in Japan) as 2,6-dimethoxy-1,4-benzoquinone (DBQ), fertaric acid and caftaric acid. We also reported that the oral intake of a partially purified fraction from yamabudo juice (yamabudo-fr) or DBQ affords significant protection against two-stage skin carcinogenesis in mice. In this study, we found that oral intake of yamabudo-fr or DBQ affords significant protection against a tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mouse model of lung tumorigenesis. Furthermore, we investigated the anti-tumorigenic mechanisms of yamabudo juice and DBQ. NNK is known to be a DNA-methylating and alkylating agent; thus, we investigated the anti-tumorigenic mechanisms of yamabudo juice and DBQ in relation to DNA methylation. Pretreatment with yamabudo-fr or DBQ dose-dependently decreased formation of O6-methylguanine and N7-methylguanine in DNA of the A549 human lung epithelial-like cell line treated with a methylating agent, 1-methyl-3-nitro-1-nitrosoguanidine. Yamabudo juice and DBQ inhibited the mutagenicity of NNK in the Ames test using Salmonella typhimurium TA1535 but not S. typhimurium YG7108, an alkylguanine DNA alkyltransferase-deficient strain (same as TA1535 but Δadast::Kmr, Δogtst::Cmr). Yamabudo juice and DBQ might accelerate the repair of DNA damage caused by NNK and reduce DNA damage to cells. We also investigated the effects of yamabudo juice and DBQ on signaling pathways in A549 cells. With or without epidermal growth factor stimulation, phosphorylation of Erk1/2, Akt and Stat3 in A549 cells was significantly decreased in the presence of yamabudo juice or DBQ, indicating that yamabudo juice and DBQ suppressed PI3K/AKT, MAPK/ERK and JAK/STAT3 signaling pathways. These results suggest that both initiation and growth/progression steps in carcinogenesis, especially anti-oxidant effects, stimulation of repair of alkyl DNA adducts and suppressed growth signaling pathways are potential anti-tumorigenic targets of yamabudo juice and DBQ in NNK-induced lung tumorigenesis.


Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Benzoquinonas/farmacologia , Carcinógenos/toxicidade , Neoplasias Pulmonares/prevenção & controle , Nitrosaminas/toxicidade , Vitis/química , Células A549 , Animais , Antimutagênicos/farmacologia , Reparo do DNA/efeitos dos fármacos , Feminino , Humanos , Camundongos , Fosforilação
14.
Molecules ; 26(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072474

RESUMO

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5-100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.


Assuntos
Antimutagênicos/química , Antioxidantes/química , Ficus/metabolismo , Extratos Vegetais/química , Animais , Ânions , Linhagem Celular , Cricetulus , Diabetes Mellitus , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Glutationa , Camundongos , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade , Mutagênicos , Estresse Oxidativo , Salmonella typhimurium/efeitos dos fármacos , Sais de Tetrazólio/química , Tiazóis/química , Vitamina K 3/química , Água
15.
Bull Exp Biol Med ; 171(1): 1-14, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34050413

RESUMO

The existing concepts of antimutagenesis are briefly reviewed. Published reports on antimutagenic and proapoptotic properties of some polyphenols and compounds of other chemical groups obtained in representative in vitro and in vivo experiments on eukaryotic test systems are discussed. The relationships between the antimutagenic and proapoptotic properties of the analyzed compounds (naringin, apigenin, resveratrol, curcumin, N-acetylcysteine, etc.) are considered in favor of the hypothesis on induced cell death as an antimutagenic tool.


Assuntos
Antimutagênicos , Acetilcisteína , Antimutagênicos/farmacologia , Morte Celular
16.
Future Microbiol ; 16: 471-485, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33960819

RESUMO

Aim: Evaluate the chemopreventive potential of the extract from P. polymyxa RNC-D. Methods: Concentrations of P. polymyxa RNC-D extract were tested in HepG2/C3A cells to assess their genotoxic (comet assay), mutagenic (micronucleus test) and antigenotoxic potential (comet assay) in vitro. Results: 400 and 40 µg/ml concentrations induced DNA lesions, whereas the 4 µg/ml induced a desmutagenic effect. Complementary tests indicated that the extract minimized the formation of reactive oxygen species induced by methyl methanesulfonate and normalized the loss of membrane potential. The quantification of cytokines indicated that TNF-α was immunostimulated by the extract. However, when administered in conjunction with the methyl methanesulfonate, the extract blocked the TNF-α release. Conclusion: The fermentation broth from P. polymyxa RNC-D showed an antigenotoxic effect, and thus the potential to be used as chemopreventive compound.


Assuntos
Antimutagênicos/metabolismo , Paenibacillus polymyxa/metabolismo , Antimutagênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Fermentação , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metanossulfonato de Metila/toxicidade , Testes de Mutagenicidade , Espécies Reativas de Oxigênio/metabolismo
17.
Food Funct ; 12(7): 3233-3245, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33877247

RESUMO

This research was aimed to assess the potential of Glechoma hederacea, Hyssopus officinalis, Lavandula angustifolia, Leonurus cardiaca, Marrubium vulgare and Sideritis scardica (Lamiaceae) methanolic, ethanolic and aqueous extracts against the damaging effects of oxidative stress using different experimental models. The chemical characterization was done spectrophotometrically by quantifying total phenolics, phenolic acids, flavonoids and flavonols in the extracts, as well as by employing HPLC-DAD technique. Moreover, DPPH assay was used to assess the extracts' radical scavenging potential. Genoprotective properties of the extracts were evaluated using plasmid pUC19 Escherichia coli XL1-Blue, whereas their antigenotoxic potential was determined using Salmonella typhimurium TA1535/pSK1002 and normal human lung fibroblasts. All of the extracts showed antioxidant activity in DPPH assay. Furthermore, the results have shown that aqueous extracts provided the best protection for plasmid DNA, while alcoholic extracts most effectively contributed to the preservation of prokaryotic DNA. Additionally, each of the tested samples significantly protected the eukaryotic cells against genomic damages. Finally, despite not showing exceptional results in DPPH assay, S. scardica extracts are regarded as the most favorable in maintaining the integrity of DNA, which might be due to high quantities of phenolics such as quercetin (up to 17.95 mg g-1), naringin (up to 5.07 mg g-1) and luteolin-7-O-glucoside (up to 3.54 mg g-1). Overall, this comprehensive concept highlights the ability of these Lamiaceae species to safeguard the DNA from reactive oxygen species, to curtail the inflicted damage and also improve the efficiency of the DNA repair mechanisms, while emphasizing the importance of polyphenols as their active principles.


Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Lamiaceae/química , Extratos Vegetais/química , Dano ao DNA/efeitos dos fármacos , Reparo do DNA , Fibroblastos/efeitos dos fármacos , Flavonoides/análise , Humanos , Testes de Mutagenicidade , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/análise , Salmonella typhimurium/metabolismo
18.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652778

RESUMO

Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of Morus alba (M. alba) against cyclophosphamide induced somatic and germinal cell damage in male rats. The ethanolic extract of M. alba (0.25, 0.5 and 1 g/kg, 2 weeks) was evaluated against cyclophosphamide (75 mg/kg, single dose) induced nuclear damage. The sampling was done after 48 h of the clastogen treatment. The somatic and germinal nuclear damage was studied by bone marrow micronucleus and sperm analysis, respectively. Serum superoxide and catalase levels were estimated to determine the antioxidant status in each group. The results were analyzed statistically to find the significant variation. The administration of M. alba for 2 weeks suppressed dose-dependently the changes induced by cyclophosphamide. M. alba (0.5 g/kg) decreased the frequency of micronucleated erythrocyte, sperm shape abnormality and enhanced the sperm count, sperm motility and polychromatic-normochromatic erythrocytes ratio significantly (p < 0.05) in comparison with the cyclophosphamide treated group. The highest tested dose of M. alba (1 g/kg) produced more prominent suppression (p < 0.01) in the cyclophosphamide-induced somatic and germinal cell defects. The results also showed significant (p < 0.05) improvement in the serum antioxidant enzymes levels with M. alba when compared with the challenge group. The lower dose of M. alba extract (0.25 g/kg) prevented the CP-induced changes but was found to be statistically insignificant. Therefore, antimutagenic potential of the high dose of the extract of M. alba is possibly due to its antioxidant nature. The ability of the M. alba extract to prevent the nuclear damage could play an important role in overcoming several mutational defects that are associated with anticancer chemotherapy.


Assuntos
Antioxidantes/farmacologia , Morus/química , Extratos Vegetais/farmacologia , Motilidade Espermática/efeitos dos fármacos , Animais , Antimutagênicos/química , Antimutagênicos/farmacologia , Antioxidantes/química , Ciclofosfamida/toxicidade , Etanol/química , Humanos , Masculino , Mutagênicos/toxicidade , Extratos Vegetais/química , Ratos
19.
Food Chem Toxicol ; 152: 112159, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33789120

RESUMO

There is increasing evidence that the excessive generation of free radicals in the human body plays a major role in the pathophysiology and development of various diseases, closely associated with oxidative damage. In this frame, the consumption of antioxidant nutrients through food or dietary supplements may prevent from the harmful effects of free radicals on human cells. This work proposes a holistic approach consisting of distinct methodologies, suitable to evaluate the antioxidant and chemoprotective activity of three novel dietary supplements, each one containing active substances with complementary properties. In the first step, this approach includes in vitro studies to evaluate the antioxidant activity of the dietary supplements by measuring the parameters of free radical scavenging capacity, of reducing power activity, as well as, their ability to protect biomolecules from oxidation. Furthermore, the evaluation of their antimutagenic and antigenotoxic effects is also presented. SubsequentlySub, the specific effects of the dietary supplements were examined in three cancer cell lines (HepG2, HeLa, MKN45), by measuring redox biomarkers such as glutathione, reactive oxygen species and thiobarbituric acid reactive substances, using flow cytometry and spectrophotometry. Our results indicate that all the dietary supplements exhibit high antioxidant, antimutagenic, antigenotoxic and lipid protective activity. The most prominent result is their capability to induce oxidative damage on cancer cells via the critical decrease of the levels of their intracellular glutathione, as well as the increase of ROS and lipid peroxidation levels after the administration of non-cytotoxic concentrations. We suggest that the proposed methodology could constitute a valuable tool for the characterization of dietary supplements based on their chemical and functional properties.


Assuntos
Anti-Inflamatórios/farmacologia , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Suplementos Nutricionais , Linhagem Celular Tumoral , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Salmonella typhimurium/efeitos dos fármacos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
20.
Mol Reprod Dev ; 88(2): 167-174, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33522057

RESUMO

Oxidative stress (OS) plays a significant role in the etiology of male infertility, resulting in the impairment of male reproduction. This condition, characterized by an imbalance in the levels of oxidizing and antioxidant species in the seminal fluid, has a harmful impact on sperm functions and DNA integrity. The present study aimed to evaluate the anti-genotoxic action of ellagic acid, a polyphenolic molecule of natural origin having a powerful antigenotoxic, anti-inflammatory and antiproliferative role. An OS condition was induced in vitro by incubating normozoospermic human semen samples in benzene for 45, 60 and 90 min. DNA integrity was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay, RAPD-PCR was performed to calculate the genome template stability, while the percentage of intracellular reactive oxygen species (ROS) was assessed by the 2', 7'-dichlorofluorescein assay. Our results showed that ellagic acid has a consistent protective effect on DNA integrity, as well as on sperm vitality and motility, by counteracting generation of intracellular ROS. The results of this study suggest ellagic acid as a suitable molecule to protect sperm DNA from oxidative stress, with a potentially significant translational impact on the management of the male infertility.


Assuntos
Antimutagênicos/farmacologia , DNA/fisiologia , Ácido Elágico/farmacologia , Espermatozoides/efeitos dos fármacos , Adulto , Antioxidantes/farmacologia , Fragmentação do DNA , DNA Nucleotidilexotransferase/metabolismo , Instabilidade Genômica , Humanos , Masculino , Técnica de Amplificação ao Acaso de DNA Polimórfico , Motilidade Espermática , Espermatozoides/fisiologia
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