RESUMO
Sterilization is a fundamental step to eliminate microorganisms prior to the application of products, especially in the food and medical industries. γ-irradiation is one of the most recommended and effective methods used for sterilization, but its effect on the properties and performance of bio-based polymers is negligible. This work is aimed at evaluating the influence of γ-radiation at doses of 5, 10, 15, 25, 30, and 40 kGy on the morphology, properties, and performance of bioplastic produced from onion bulb (Allium cepa L.), using two hydrothermal synthesis procedures. These procedures differ in whether the product is washed or not after bioplastic synthesis, and are referred to as the unwashed hydrothermally treated pulp (HTP) and washed hydrothermally treated pulp (W-HTP). The morphological analysis indicated that the film surfaces became progressively rougher and more irregular for doses above 25 kGy, which increases their hydrophobicity, especially for the W-HTP samples. In addition, the FTIR and XRD results indicated that irradiation changed the structural and chemical groups of the samples. There was an increase in the crystallinity index and a predominance of the interaction of radiation with the hydroxyl groups-more susceptible to the oxidative effect-besides the cleavage of chemical bonds depending on the γ-radiation dose. The presence of soluble carbohydrates influenced the mechanical behavior of the samples, in which HTP is more ductile than W-HTP, but γ-radiation did not cause a change in mechanical properties proportionally to the dose. For W-HTP, films there was no mutagenicity or cytotoxicity-even after γ-irradiation at higher doses. In conclusion, the properties of onion-based films varied significantly with the γ-radiation dose. The films were also affected differently by radiation, depending on their chemical composition and the change induced by washing, which influences their use in food packaging or biomedical devices.
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The development of new drugs based on metal complexes requires a detailed analysis of their biological endpoints. In this study, we report the genotoxic profile and influence on cell proliferation and death of the oxovanadium(IV) complex with orotic acid ([VO(C5H4N2O4)2], VO(oro)). Human hepatocellular carcinoma cells (HepG2) were the most sensitive tumor cells to VO(oro), which interfered with the integrity of cell membranes and proliferative capacity in a dose-dependent manner, inducing cell death by apoptosis. Regarding genotoxicity, VO(oro) did not induce considerable levels of DNA damage in HepG2 cells (comet test) and gene mutations (Ames test). However, it caused a statistically significant increase in the frequency of micronuclei at the highest concentration tested (12.5 µmol.L-1), indicating aneuploidy and clastogenicity. The data presented here provide information on various biological aspects of the VO(oro) complex, which may allow the elucidation of its mechanism of action as a possible therapeutic agent.
Assuntos
Dano ao DNA , Ácido Orótico , Humanos , Mutagênicos/toxicidade , Mutação , Morte CelularRESUMO
For the first time, we herein report on the syntheses of two new Ru(II)/bipyridine/phenanthroline complexes containing lapachol as ligand: complex (1), [Ru (bipy)2(Lap)]PF6 and complex (2), [Ru(Lap)(phen)2]PF6, where bipy = 2,2'-bipyridine and ph en = 1,10-phenanthroline; Lap = lapachol (2-hydroxy-3-(3-methylbut-2-en-1- yl)naphthalene-1,4-dione). The complexes were synthesized and characterized by elemental analyses, molar conductivity, mass spectrometry, ultraviolet-visible and infrared spectroscopies, nuclear magnetic resonance (1H, 13C), and single crystal X-ray diffraction, for complex (2). In addition, in vitro cytotoxicity was tested against six cancer cells: A549 (lung carcinoma); DU-145 (human prostate carcinoma); HepG2 (human hepatocellular carcinoma), PC-3 (human prostate adenocarcinoma); MDA-MB-231 (human breast adenocarcinoma); Caco-2 (human colorectal adenocarcinoma), and against two non-cancer cells, FGH (human gingival normal fibroblasts) and PNT-2 (prostate epithelial cells). Complex (1) was slightly more toxic and selective than complex (2) for all cell lines, except against the A549 cells, where (2) was more potent than complex (1). The complexes induced an increase in the reactive oxygen species, and the co-treatment with N-acetyl-L-cysteine remarkably suppressed the ROS generation and prevented the reduction of cell viability, suggesting that the cytotoxicity of the complexes is related to the ROS-mediated pathway. Further studies indicated that the complexes may bind to DNA via minor groove interaction. Our studies also revealed that free Lap induces gene mutations in Salmonella Typhimurium, nevertheless, the complexes demonstrated the absence of genotoxicity by the Ames test. The present study provides a relevant contribution to understanding the anti-cancer potential and genetic toxicological events of new ruthenium complexes containing the lapachol molecule as a ligand.
Assuntos
Adenocarcinoma , Antineoplásicos , Carcinoma , Complexos de Coordenação , Rutênio , Masculino , Humanos , Fenantrolinas , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Espécies Reativas de Oxigênio/metabolismo , Ligantes , Células CACO-2 , Rutênio/química , Antineoplásicos/química , Linhagem Celular TumoralRESUMO
Copaifera langsdorffii Desf. is a plant found in South America, especially in Brazil. Oleoresin and the leaves of this plant is used as a popular medicinal agent. However, few studies on the chemical composition of aerial parts and related biological activities are known. This study aimed to examine the cytotoxic, genotoxic, and antigenotoxic potential of C. langsdorffii aerial parts hydroalcoholic extract (CLE) and two of its major compounds afzelin and quercitrin. The cytotoxic and antigenotoxic potential of CLE was determined as follows: 1) against genotoxicity induced by doxorubicin (DXR) or methyl methanesulfonate (MMS) in V79 cells; 2) by direct and indirect-acting mutagens in Salmonella typhimurium strains; and 3) by MMS in male Swiss mice. The protective effects of afzelin and quercitrin against DXR or MMS were also evaluated in V79 and HepG2 cells. CLE was cytotoxic as evidenced by clonogenic efficiency assay. Further, CLE did not induce a significant change in frequencies of chromosomal aberrations and micronuclei; as well as number of revertants in the Ames test demonstrating absence of genotoxicity. In contrast, CLE was found to be antigenotoxic in mammalian cells. The results also showed that CLE exerted inhibitory effect against indirect-acting mutagens in the Ames test. Afzelin and quercitrin did not reduce genotoxicity induced by DXR or MMS in V79 cells. However, treatments using afzelin and quercitrin decreased MMS-induced genotoxicity in HepG2 cells. The antigenotoxic effect of CLE observed in this study may be partially attributed to the antioxidant activity of the combination of major components afzelin and quercitrin.
Assuntos
Dano ao DNA/efeitos dos fármacos , Fabaceae/química , Manosídeos/farmacologia , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Quercetina/análogos & derivados , Animais , Doxorrubicina/toxicidade , Células Hep G2 , Humanos , Masculino , Metanossulfonato de Metila/toxicidade , Camundongos , Mutagênicos/farmacologia , Mutagênicos/toxicidade , Extratos Vegetais/química , Folhas de Planta/química , Quercetina/farmacologia , Salmonella typhimurium/efeitos dos fármacosRESUMO
Helicobacter pylori inhabits the gastric epithelium and can promote the development of gastric disorders, such as peptic ulcers, acute and chronic gastritis, mucosal lymphoid tissue (MALT), and gastric adenocarcinomas. To use nanotechnology as a tool to increase the antibacterial activity of silver I [Ag(I)] compounds, this study suggests a new strategy for H. pylori infections, which have hitherto been difficult to control. [Ag (PhTSC·HCl)2] (NO3)·H2O (compound 1) was synthesized, characterized, and loaded into polymeric nanoparticles (PN1). PN1 had been developed by nanoprecipitation with poly(ε-caprolactone) polymer and poloxamer 407 surfactant. System characterization assays showed that the PNs had adequate particle sizes and ζ-potentials. Transmission electron microscopy confirmed the formation of polymeric nanoparticles (PNs). Compound 1 had a minimum inhibitory concentration for H. pylori of 3.90 µg/mL, which was potentiated to 0.781 µg/mL after loading. The minimum bactericidal concentration of 7.81 µg/mL was potentiated 5-fold to 1.56 µg/mL in PN. Compound 1 loaded in PN1 displayed better activity for H. pylori biofilm formation and mature biofilm. PN1 reduced the toxicity of compound 1 to MRC-5 cells. Loading compound 1 into PN1 inhibited the mutagenicity of the free compound. In vivo, the system allowed survival of Galleria mellonella larvae at a concentration of 200 µg/mL. This is the first demonstration of the antibacterial activity of a silver complex enclosed in polymeric nanoparticles against H. pylori.
Assuntos
Antibacterianos/farmacologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Nanopartículas Metálicas/química , Polímeros/química , Compostos de Prata/farmacologia , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Fibroblastos/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Humanos , Concentração Inibidora 50 , Larva/efeitos dos fármacos , Lepidópteros/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Tamanho da Partícula , Compostos de Prata/químicaRESUMO
Considering the promising previous results of Cu (II) complexes with isoniazid active ligand against Mycobacterium tuberculosis, the main causative agent of tuberculosis, novel biological assays evaluating its toxicogenic potential were performed to ensure the safe use. The genotoxicity/mutagenicity of the complexes CuCl2(INH)2.H2O (I1), Cu(NCS)2(INH)2.5H2O (I2) and Cu(NCO)2(INH)2.4H2O (I3) was evaluated by the Comet, Micronucleus-cytome and Salmonella microsome (Ames test) assays. The cell viability using resazurin assay indicated that I1, I2 e I3 had moderate to low capacity to reduce the viability of colorectal cells (Caco-2), liver cells (HepG2), lung cells (GM 07492-A and A549) and endothelial cells (HU-VE-C). On genotoxicity/mutagenicity, I1 complex did not induce sizable levels of DNA damage in HepG2 cells (Comet assay), and gene (Ames test) and chromosomal (Micronucleus-cytome assay) mutations. Already, I2 and I3 complexes were considered mutagenic in the highest concentrations used. In light of the above, these results contribute to valuable data on the safe use of Cu(II) complexes. Considering the absence of mutagenicity and cytotoxicity of I1, this complex is a potential candidate for the development of a new drug to the treatment tuberculosis, while I2 and I3 require caution in its use.
Assuntos
Antituberculosos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Células A549 , Antituberculosos/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complexos de Coordenação/química , Cobre/química , Células Hep G2 , Humanos , Isoniazida/química , Ligantes , Testes de Sensibilidade Microbiana , Conformação Molecular , Testes de Mutagenicidade , Mycobacterium tuberculosis/citologiaRESUMO
The production of films and coatings from onion (Allium cepa L.) to be applied as packaging is attractive, due to its high nutritional and therapeutic value. Also, it can collaborate to minimize environmental impacts caused by the improper disposal of products made from plastics. However, despite it being an innovative and novel proposal, onion films for the development of edible packaging should be evaluated before being considered nontoxic and safe for human consumption. Thus, the objective of the present study was to elucidate the cytotoxic and mutagenic profile of eluates of polymer films of Allium cepa L. obtained by the casting process and to verify their safety for commercial purposes. The analysis of cellular viability demonstrated greater cytotoxicity for unwashed hydrothermally treated pulp (HTP) than for films of washed hydrothermally treated pulp (W-HTP). Regarding the mutagenic activity, the HTP and W-HTP films were not able to statistically increase the frequencies of the biomarkers for chromosome damage (micronucleus test) at the tested concentrations. However, the HTP films showed signs of mutagenicity in the Ames test (gene mutations), suggesting caution in their use. The detection of genotoxicity is highly recommended in order to avoid the risk of genotoxic exposure to mutagens and carcinogens. In conclusion, the absence of mutagenicity and cytotoxicity observed in this study is extremely relevant, because it provides support for toxicogenic properties of the Allium cepa films with promising applicability in the food industry. PRACTICAL APPLICATION: The bioplastics made from onion bulbs are multifunctional materials, which requires safety profile assessment. The results of the mutagenicity and cytotoxicity tests suggests that especially the W-HTP films are harmless, supporting at the first level of evidence, its safety potential to be used in the food industry (food films), biodegradable packaging, and biomaterials (substrates for drug delivery system).
Assuntos
Embalagem de Alimentos/instrumentação , Cebolas/química , Extratos Vegetais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Qualidade de Produtos para o Consumidor , Dano ao DNA/efeitos dos fármacos , Filmes Comestíveis , Humanos , Mutagênese , Testes de Mutagenicidade , Extratos Vegetais/farmacologia , Raízes de Plantas/químicaRESUMO
Trees of the Copaifera genus are native to the tropical regions of Latin America and Western Africa. Copaifera sp is widely used as a popular medicine and it has various ethnopharmacological indications, including gonorrhea, bronchitis, asthma, skin ulcers, ulcers, sore throat, uterine infections, general inflammations, cancer, and leishmanioses. Kaurenoic acid is a naturally occurring diterpene found in Copaifera and has been used as an anti-inflammatory, treatment of ulcer, leishmaniasis, and cancer. Bearing in mind the fact that the Ames test is an excellent tool to assess the safety of extracts, oils, and phytochemicals isolated from medicinal plants, from it, we evaluate the mutagenic potential of four species, between oleoresins (C. oblongifolia; C. langsdorffii) and leaves extracts (C. lucens; C. multijuga), of the Copaifera genus and also of kaurenoic acid, which is one of its major compounds. The results showed that the Copaifera spp. and kaurenoic acid did not induce an increase in the number of revertant colonies, without mutagenic effect in experiments, in the all concentrations evaluated by Ames test. The results obtained in our study support the safe use of the Copaifera genus medicinal plants selected and of kaurenoic acid.
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Foodborne diseases (FBDs) are a serious public health concern worldwide. In this scenario, preservatives based on natural products, especially plants, have attracted researchers' attention because they offer potential antimicrobial action as well as reduced health impact. The genus Copaifera spp., which is native of tropical South America and West Africa, contains several species for which pharmacological activities, including antibacterial effects, have been described. On the basis of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), antibiofilm activity (inhibition and eradication), preservative capacity, and Ames test, we evaluated the antibacterial, preservative, and mutagenic potential of Copaifera spp. oleoresins against the causative agents of FBDs. The Copaifera duckei, Copaifera reticulata, Copaifera paupera, and Copaifera pubiflora oleoresins displayed promising MIC/MBC values-from 12.5 to 100 µg/mL-against Staphylococcus aureus (American Type Culture Collection [ATCC] 29213), Listeria monocytogenes (ATCC 15313), and Bacillus cereus (ATCC 14579). C. duckei, C. reticulata, C. paupera, and C. pubiflora oleoresin concentrations ranging from 25 to 200 µg/mL and from 100 to 400 µg/mL inhibited biofilm formation and eradicated biofilms, respectively. The oleoresins did not exert mutagenic effects and had superior food preservative action to sodium benzoate (positive control). In conclusion, Copaifera oleoresins exhibit potential antibacterial activity and are not mutagenic, which makes them a promising source to develop novel natural food preservatives to inhibit foodborne pathogens.
RESUMO
In view of the biological activities and growing therapeutic interest in oleoresin obtained from Copaifera multijuga, this study aimed to determine the genotoxic and antigenotoxic potential of this oleoresin (CMO) and its chemical marker, diterpene (-)-copalic acid (CA). The micronucleus (MN) assay in V79 cell cultures and the Ames test were used for in vitro analyses, as well as MN and comet assays in Swiss mice for in vivo analyses. The in vitro genotoxicity/mutagenicity results showed that either CMO (30, 60, or 120 µg/ml-MN assay; 0.39-3.12 mg/plate-Ames test) or CA (2.42; 4.84, or 9.7 µg/ml-MN assay; 0.39-3.12 mg/plate-Ames test) did not induce a significant effect on the frequency of MN and number of revertants, demonstrating an absence of genotoxic and mutagenic activities, respectively, in vitro. In contrast, these natural products significantly reduced the frequency of MN induced by methyl methanesulfonate (MMS), and exerted a marked inhibitory effect against indirect-acting mutagens in the Ames test. In the in vivo test system, animals treated with CMO (6.25 mg/kg b.w.) exhibited a significant decrease in rate of MN occurrence compared to those treated only with MMS. An antigenotoxic effect of CA was noted in the MN test (1 and 2 mg/kg b.w.) and the comet assay (0.5 mg/kg b.w.). Data suggest that the chemical marker of the genus Copaifera, CA, may partially be responsible for the observed chemopreventive effect attributed to CMO exposure. ABBREVIATIONS: 2-AA, 2-anthramine; 2-AF, 2-aminofluorene; AFB1, aflatoxin B1; B[a]P, benzo[a]pyrene; BOD, biological oxygen demand; BPDE, benzo[a]pyrene-7,8-diol-9,10-epoxide; CA, (-)-copalic acid; CMO, oleoresin of Copaifera multijuga, DMEM, Dulbecco`s Modified Eagles`s Medium; DMSO, dimethylsulfoxide; EMBRAPA, Brazilian agricultural research corporation; GC-MS, gas chromatography-mass spectrometry; HAM-F10, nutrient mixture F-10 Ham; HPLC, high performance liquid chromatography; LC-MS, liquid chromatography-mass spectrometry; MI, mutagenic index; MMC, mitomycin C; MMS, methyl methanesulfonate; MN, micronucleus; MNPCE, micronucleated polychromatic erythrocyte; NCE, normochromatic erythrocyte; NDI, nuclear division index; NMR, nuclear magnetic resonance; NPD, 4-nitro-o-phenylenediamine; PBS, phosphate-buffered saline; PCE, polychromatic erythrocyte; SA, sodium azide; V79, Chinese hamster lung fibroblast.
Assuntos
Antimutagênicos/farmacologia , Diterpenos/farmacologia , Fabaceae/química , Extratos Vegetais/farmacologia , Animais , Ensaio Cometa , Cricetulus , Fibroblastos/efeitos dos fármacos , Pulmão , Masculino , Camundongos , Testes para Micronúcleos , Testes de MutagenicidadeRESUMO
Arrabidaea brachypoda (DC.) Bureau is a shrub native Cerrado, known as "cipó-una", "tintureiro" or "cervejinha do campo" and popularly used in Southeastern and Northeastern Brazil to treatment of kidney stones and painful joints (arthritis). Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the principal objective of this study was to assess the mutagenic and estrogenic activities of the hydroalcoholic extracts of the leaves, stalks, roots, their respective fractions and isolated compounds of A. brachypoda. The mutagenic activity was evaluated by the Ames test on Salmonella typhimurium strains TA98, TA97a, TA100 and TA102, in the absence (-S9) and presence (+S9) of metabolic activation system. In the RYA was used Saccharomyces cerevisiae engineered strain BY4741 (MATaura3Δ0 leu2Δ0 his3Δ1 met15Δ0) which reproduce the natural pathway of genetic control by estrogens in vertebrate cells; it has the advantage of its simplicity and a high throughput. All extracts and aqueous fraction of leaves A. brachypoda were mutagenic. The crude extract is more active than the fraction, suggesting a synergic effect. Only hydroalcoholic extracts of leaves and roots of A. brachypoda showed significant estrogenic activity, with ERα-dependent transcriptional activation activity. The obtained results in this study showed the presence of compounds capable of interacting with the estrogen receptor and to induce damage in the genetic material. Thus, we demonstrated the risk which the population is subjected due to indiscriminate use of extracts without detailed study.
Assuntos
Bignoniaceae/química , Estrogênios/metabolismo , Medicina Tradicional/efeitos adversos , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Animais , Brasil , Receptor alfa de Estrogênio/metabolismo , Humanos , Medicina Tradicional/métodos , Testes de Mutagenicidade/métodos , Folhas de Planta/toxicidade , Raízes de Plantas/toxicidade , Caules de Planta/toxicidade , Ratos , Ratos Sprague-Dawley , Medição de Risco , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genéticaRESUMO
Tuberculosis is a top infectious disease killer worldwide, caused by the bacteria Mycobacterium tuberculosis. Increasing incidences of multiple drug-resistance (MDR) strains are emerging as one of the major public health threats. However, the drugs in use are still incapable of controlling the appalling upsurge of MDR. In recent years a marked number of research groups have devoted their attention toward the development of specific and cost-effective antimicrobial agents against targeted MDR-Tuberculosis. In previous studies, ruthenium(II) complexes (SCAR) have shown a promising activity against MDR-Tuberculosis although few studies have indeed considered ruthenium toxicity. Therefore, within the preclinical requirements, we have sought to determine the cyto-genotoxicity of three SCAR complexes in this present study. The treatment with the SCARs induced a concentration-dependent decrease in cell viability in CHO-K1 and HepG2 cells. Based on the clonogenic survival, SCAR 5 was found to be more cytotoxic while SCAR 6 exhibited selectivity action on tumor cells. Although SCAR 4 and 5 did not indicate any mutagenic activity as evidenced by the Ames and Cytokinesis block micronucleus cytome assays, the complex SCAR 6 was found to engender a frameshift mutation detected by Salmonella typhimurium in the presence of S9. Similarly, we observed a chromosomal damage in HepG2 cells with significant increases of micronuclei and nucleoplasmic bridges. These data indicate that SCAR 4 and 5 complexes did not show genotoxicity in our models while SCAR 6 was considered mutagenic. This study presented a comprehensive genotoxic evaluation of SCAR complexes were shown to be genotoxic in vitro. All in all, further studies are required to fully elucidate how the properties can affect human health.
Assuntos
Antituberculosos/toxicidade , Complexos de Coordenação/toxicidade , Mutagênicos/toxicidade , Rutênio/toxicidade , Animais , Células CHO , Cricetulus , Citocinese/efeitos dos fármacos , Células Hep G2 , Humanos , Testes para Micronúcleos , Rutênio/química , Salmonella typhimurium/efeitos dos fármacosRESUMO
Machaerium hirtum (Vell.) Stellfeld (M.hirtum) is a plant known as 'jacarandá-bico-de-pato' whose bark is commonly used against diarrhea, cough and cancer. The aim of this study was to phytochemically characterise the hydroethanolic extract of this plant, investigate its antimutagenic activities using the Ames test and evaluate its effects on cell viability, genomic instability, gene expression and cell protection in human hepatocellular carcinoma cells (HepG2). Antimutagenic activity was assessed by simultaneous pre- and post-treatment with direct and indirect mutagens, such as 4-nitro-o-phenylenediamine (NPD), mitomycin C (MMC), benzo[a]pyrene (B[a]P) and aflatoxin B1 (AFB1), using the Ames test, cytokinesis blocking micronucleus and apoptosis assays. Only 3 of the 10 concentrations evaluated in the MTT assay were cytotoxic in HepG2 cells. Micronucleated or apoptotic cells were not observed with any of the tested concentrations, and there were no mutagenic effects in the bacterial system. However, the Nuclear Division Index and flow cytometry data showed a decrease in cell proliferation. The extract showed an inhibitory effect against direct (NPD) and indirect mutagens (B[a]P and AFB1). Furthermore, pre- and post-treated cells showed significant reduction in the number of apoptotic and micronucleated cells. This effect is not likely to be associated with the modulation of antioxidant genes, as shown by the RT-qPCR results. Six known flavonoids were identified in the hydroethanolic extract of Machaerium hirtum leaves, and their structures were elucidated by spectroscopic and spectrophotometric methods. The presence of the antioxidants apigenin and luteolin may explain these protective effects, because these components can inhibit the formation of reactive species and prevent apoptosis and DNA damage. In conclusion, the M.hirtum extract showed chemopreventive potential and was not hazardous at the tested concentrations in the experiments presented here. Moreover, this extract should be investigated further as a chemopreventive agent.
Assuntos
Antimutagênicos/farmacologia , Fabaceae/química , Extratos Vegetais/farmacologia , Antimutagênicos/química , Antimutagênicos/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/toxicidade , Citometria de Fluxo , Expressão Gênica , Humanos , Micronúcleos com Defeito Cromossômico , Testes para Micronúcleos , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genéticaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Serjania marginata (Sapindaceae), a medicinal plant commonly found in the Brazilian Cerrado, Paraguay, Bolivia and Argentina, is also known as "cipó-uva" or "cipó-timbó". Ethnopharmacological studies indicate that the leaves from this medicinal plant are used in folk medicine to treat gastric pain. The overall objective of this study was to evaluate the gastroprotective and healing effect of the hydroalcoholic extract obtained from S. marginata (HESM) leaves using rodent experimental models. As part of the integrative study of this medicinal plant, we also evaluated the acute toxicity, antimicrobial, antidiarrheal, (anti)mutagenic, and hemodynamic effects. MATERIAL AND METHODS: We performed a pharmacological study to test the acute toxicity and antimutagenic effect (Ames assay) of the HESM. The HESM was tested against different necrosis-promoting agents and experimental manipulations, such as absolute ethanol, cysteamine, pyloric ligature, and ischemia-reperfusion (I/R) injury. The gastroprotective effect of the HESM was assessed by analyzing the gastric juice (volume, pH, total acidity) and the mucus in the gastric mucosa from rats. We assessed the levels of NO, sulfhydryl compounds, PGE2, vanilloid receptor, glutathione (GSH), and malondialdehyde (MDA), as well as the myeloperoxidase (MPO) activity. The gastric healing effects of the HESM were evaluated during 7 or 14 days of treatment. The intestinal motility, antidiarrheal action, and antibacterial effects (microdilution methods) of the HESM were also evaluated. RESULTS: The phytochemical analysis of the HESM revealed the presence of saponins, flavonoid glycosides, and tannins. The extract exhibited no sign of acute toxicity or mutagenic effect in vitro. In contrast, this extract exhibited a protective effect against the mutagenic action of direct- and indirect-acting mutagens. Only the oral administration of HESM (250mg/kg) significantly decreased the severity of gastric damage induced by ethanol (60.13%) and I/R (58.31%). The HESM exerts its gastroprotective effects by decreasing the MPO and MDA activities in the gastric tissue and by increasing the amount of adherent mucus covering the gastric mucosa. In vitro, the extract also displayed evident antimicrobial effects against Helicobacter pylori. However, the preventive effect of the HESM was not accompanied by an ulcer-healing effect. The treatment with HESM (14 days) significantly increased gastric lesions in 99% of the tested animals compared with the control group. This result represents a highly relevant piece of evidence that should resonate as an alert against the chronic use of this medicinal plant as an antiulcer in folk medicine. CONCLUSIONS: Despite the anti-H. pylori and gastroprotective actions of S. marginata in experimental models, the gastric injuries aggravation induced after chronic treatment with the HESM argues against the use of this plant species in folk medicine.
Assuntos
Antiulcerosos/farmacologia , Extratos Vegetais/farmacologia , Sapindaceae/química , Úlcera Gástrica/prevenção & controle , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Antiulcerosos/isolamento & purificação , Antiulcerosos/toxicidade , Antidiarreicos/isolamento & purificação , Antidiarreicos/farmacologia , Antidiarreicos/toxicidade , Modelos Animais de Doenças , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Masculino , Medicina Tradicional , Camundongos , Extratos Vegetais/toxicidade , Folhas de Planta , Ratos , Ratos Wistar , Fatores de Tempo , Testes de Toxicidade AgudaRESUMO
A toracotomia é um procedimento que provoca intensa dor no pós-operatório. Para amenizá-la, várias técnicas de analgesia são descritas, sem, contudo, mostrar superioridade comprovada uma sobre as outras. Apresenta-se um caso de analgesia para toracotomia com cateteres multiperfurados e bomba elastomérica. Relato do caso: paciente com proposta de toracotomia exploradora devido à fratura brônquica por trauma torácico compressivo. Planejada a realização de anestesia geral e peridural torácica para analgesia, porém o paciente apresentava múltiplas lesões dermatológicas difusas pelo dorso. Realizadas então anestesia geral e analgesia com implantação de cateteres multiperfurados e infusão contínua de anestésico local por bomba elastomérica. Concluiu-se que as opções para realização de uma boa analgesia pós-operatória para toracotomia são muitas e novas técnicas vêm surgindo e ganhando espaço. A utilização de cateteres multiperfurados pode ser considerada uma opção para pacientes que tenham contraindicação à peridural torácica.
Thoracotomy is a procedure that causes intense pain in the postoperative period. Several analgesia techniques are described to ease this pain, however, without showing a proven superiority of one over the other. A case of analgesia for thoracotomy with multi-perforated catheters and elastomeric pump is presented. Case report: a patient with proposedexploratory thoracotomy due to bronchial fracture by compressive chest trauma. The general anesthesia and thoracic epidural for analgesia were planned, however, the patient presented multiple diffuse dorsal skin lesions. General anesthesia and analgesia were then performed with the implantation of multi-perforated catheters and continuous infusion of local anesthetic through an elastomeric pump. It was concluded that the optionsfor performing a good postoperative analgesia for thoracotomy are many and that new techniques are emerging and gaining space. The use of multi-perforated catheters can be considered an option for patients who have a contraindication to thoracic epidural.
RESUMO
Terminalia is a genus of Combretaceous plants widely distributed in tropical and subtropical regions. Thus, the aim of this study was to quantify the majority compounds of the hydroalcoholic extract (7 : 3, v/v) of the leaves from T. catappa by HPLC-PDA, chemically characterize by hyphenated techniques (HPLC-ESI-IT-MS(n)) and NMR, and evaluate its mutagenic activity by the Salmonella/microsome assay on S. typhimurium strains TA98, TA97a, TA100, and TA102. The quantification of analytes was performed using an external calibration standard. Punicalagin is the most abundant polyphenol found in the leaves. The presence of this compound as a mixture of anomers was confirmed using HPLC-PDA and (1)H and (13)C NMR. Mutagenic activity was observed in strains TA100 and TA97a. As the extract is a complex mixture of punicalagin, its derivatives, and several other compounds, the observed mutagenicity may be explained in part by possible synergistic interaction between the compounds present in the extract. These studies show that mutagenic activity of T. catappa in the Ames test can only be observed when measured at high concentrations. However, considering the mutagenic effects observed for T. catappa, this plant should be used cautiously for medicinal purposes.
RESUMO
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-ß-glucopyranoside, 7=7-methoxyluteolin-6-C-ß-glucopyranoside, 8=7,3'-dimethoxyluteolin-6-C-ß-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.
Assuntos
Antimutagênicos/farmacologia , Eriocaulaceae/química , Estrogênios/farmacologia , Flavonas/farmacologia , Xantonas/farmacologia , Antimutagênicos/isolamento & purificação , Antimutagênicos/toxicidade , Quimioprevenção , Estrogênios/isolamento & purificação , Estrogênios/toxicidade , Flavonas/isolamento & purificação , Flavonas/toxicidade , Humanos , Metanol/química , Mutagênicos/toxicidade , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Salmonella/efeitos dos fármacos , Xantonas/isolamento & purificação , Xantonas/toxicidadeRESUMO
Rosmarinic acid (RA) is a naturally occurring phenolic compound, which contributes to the beneficial and health-promoting effects of herbs, spices and medicinal plants. RA has shown several biological activities, such as hepatoprotective, anti-inflammatory, antiangiogenic, antitumor, antidepressant, antineurodegenerative, HIV-1 inhibitory and antioxidant effects. The aim of this study was to investigate the ability of RA to prevent chemically induced chromosome breakage or loss and primary DNA damage using the micronucleus and comet assays with V79 cells, respectively. The chemotherapeutic agent doxorubicin (DXR; 0.5 microg ml(-1)) was used as the DNA-damaging agent. The cultures were treated with different concentrations of RA (0.28, 0.56 and 1.12 mm) alone or in combination with DXR. The results showed that RA exerted no genotoxic effect, but significantly reduced the frequency of micronuclei and the extent of DNA damage induced by DXR at the three concentrations tested. The antioxidant activity of RA might be involved in the reduction of DXR-induced DNA damage observed in the present study.
Assuntos
Antimutagênicos/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Animais , Antimutagênicos/química , Antimutagênicos/isolamento & purificação , Antineoplásicos/toxicidade , Linhagem Celular , Quimioprevenção , Quebra Cromossômica/efeitos dos fármacos , Deleção Cromossômica , Cinamatos/química , Cinamatos/isolamento & purificação , Ensaio Cometa , Cricetinae , Cricetulus , Dano ao DNA/efeitos dos fármacos , Depsídeos/química , Depsídeos/isolamento & purificação , Doxorrubicina/toxicidade , Fibroblastos , Testes para Micronúcleos , Mutagênicos/toxicidade , Concentração Osmolar , Folhas de Planta/química , Rosmarinus/química , Ácido RosmarínicoRESUMO
Baccharis dracunculifolia DC (Asteraceae), a native plant from Brazil, have been used as an antipyretic, stomachic and health tonic in Brazil. The objective of the present study was to investigate the potential mutagenic effect of B. dracunculifolia ethyl acetate extract (Bd-EAE) and its influence on the mutagenicity induced by the chemotherapeutic agent doxorubicin (DXR) using the rat bone marrow and peripheral blood micronucleus test. Wistar rats were divided into 10 treatment groups. Five groups received DXR (90 mg/kg body weight, b.w., intraperitoneally) to induce mutagenicity and three of these groups received a single oral dose of Bd-EAE at a concentration of 6, 12 or 24 mg/kg b.w. prior to DXR administration. A vehicle-treated control group and Bd-EAE control groups were also included. The results showed that Bd-EAE itself was not mutagenic, in the rat micronucleus assay. In animals treated with Bd-EAE and DXR, the number of MNPCEs was significantly decreased compared to animals receiving DXR alone. HPLC analysis of the extract obtained permitted the identification of the following phenolic compounds: caffeic acid, p-coumaric acid, aromadendrin-4'O-methyl ether, 3-prenyl-p-coumaric acid (drupanin), 3,5-diprenyl-p-coumaric acid (artepillin C) and baccharin. The putative antioxidant activity or the interference of one or more of the active compounds of Bd-EAE with mutagenic metabolic pathways may explain its effect on DXR mutagenicity.