RESUMO
Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and mutagenicity induced by the alkylating agent methyl methanesulfonate (MMS). In this study, 3-month-old Swiss albino male mice (N = 66) were divided into 11 groups for experimentation. Experiments were performed by administering lyophilized RJ (150 mg/kg, 300 mg/kg, and 1000 mg/kg) or water via gavage as pre- and posttreatment processes with the alkylating agent MMS. After treatment, blood samples were collected from the mice via an incision at the end of the tail to conduct comet assays at times of 24 h and 48 h posttreatment. The mice were then euthanized to remove the bone marrow for a micronucleus test. Overall, regardless of dose, RJ did not exhibit genotoxic, mutagenic activity and the administration of high doses, mainly in the form of posttreatment, presented antigenotoxic and antimutagenic actions. Further, a dose-response correlation was observed in the RJ posttreatment groups. These results demonstrate that RJ administration was effective in reversing the damage caused by the alkylating agent MMS.
Assuntos
Alquilantes , Dano ao DNA , Camundongos , Abelhas , Animais , Alquilantes/toxicidade , Ácidos Graxos/farmacologia , Ensaio Cometa , Metanossulfonato de Metila/toxicidade , Mutagênicos/toxicidadeRESUMO
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/metabolismoRESUMO
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
Persea americana Mill., commonly known as avocado, is a tree native to Central America that is widely used as a food source and for the treatment of diseases. This plant has various biological properties such as analgesic, anti-inflammatory and total cholesterol-lowering activity. In view of its pharmacological potential, we conducted a toxicogenetic study of the fruit pulp oil of P. americana (PAO) and investigated its influence on genotoxicity induced by methyl methanesulfonate (MMS) and doxorubicin. V79 cells and Swiss mice were used for the assays. The results showed no genotoxic effects of PAO in the in vitro or in vivo test systems. However, the highest PAO dose tested led to an increase in the levels of aspartate aminotransferase, indicating hepatic/tissue damage. This effect may be related to high concentrations of palmitic acid, the main component of PAO. Furthermore, PAO was effective in reducing the chromosome damage induced by MMS and doxorubicin. These results contribute to the safety assessment of PAO as a medicinal plant for human use.
Assuntos
Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Frutas/química , Instabilidade Genômica/efeitos dos fármacos , Persea/química , Extratos Vegetais/toxicidade , Toxicogenética/métodos , Animais , Antibióticos Antineoplásicos/toxicidade , Aspartato Aminotransferases/metabolismo , Bioensaio/métodos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cricetulus , Doxorrubicina/toxicidade , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Metanossulfonato de Metila/toxicidade , Camundongos , Testes para MicronúcleosRESUMO
Solanum cernuum Vell is a Brazilian shrub or small tree, restricted to Southeast states of the country. The leaves are commercialized as "panacéia" and indicated for the treatment of urinary disorders, gonorrhea, scabies, skin diseases and as desobstruent, diuretic and antiarrhythmic. The hydroalcholic extract is active in the treatment of gastric ulcer. The aim of this study was to evaluate the genotoxic and antigenotoxic potential of S. cernuum hydroalcoholic extract (SC) in Swiss mice by micronucleus and comet assays. The animals were treated by gavage with the doses of 500, 1000 and 2000mg/kg body weight (b.w.). For antigenotoxicity assessment, the doses of 15, 30, 60, 120 and 240mg/kg b.w SC were administered simultaneously with the mutagen methyl methanesulfonate (MMS, 40mg/kg b.w., i.p.). The results showed that the SC was not genotoxic in both micronucleus and comet assays. On the other hand, the treatment with the lowest dose of SC (15mg/kg b.w.) plus MMS showed a statistically significant reduction in the frequency of micronuclei compared to treatment only with MMS. For the comet assay, significant reduction in extensions of DNA damage was observed in all treatments with SC combined with MMS in comparison with only MMS. The antigenotoxic activity observed for the SC may be due to the antioxidant potential of the compounds present in the extract such as guanidine alkaloids and flavonoids.
Assuntos
Cromossomos de Mamíferos/metabolismo , Dano ao DNA/genética , Genoma , Metanossulfonato de Metila/toxicidade , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Solanum/química , Animais , Cromatografia Líquida de Alta Pressão , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Masculino , Camundongos , Folhas de Planta/químicaRESUMO
CONTEXT: Solanum lycocarpum A. St.-Hil. (Solanaceae), popularly known as 'fruta-do-lobo' (wolf fruit), 'lobeira' and 'jurubebão', is commonly used by native people of Central Brazil in powder form or as a hydroalcoholic extract for the management of diabetes and obesity and to decrease cholesterol levels. OBJECTIVE: The present study determines the possible cytotoxic, genotoxic and antigenotoxic activities of hydroalcoholic extract of the S. lycocarpum fruits (SL). MATERIALS AND METHODS: The clonogenic efficiency assay was used to determine the cytotoxicity. Three concentrations of SL (16, 32 and 64 µg/mL) were used for the evaluation of its genotoxic and antigenotoxic potential on V79 cells using the micronucleus and comet assays. In the antigenotoxicity assays, the cells were treated simultaneously with SL and the alkylating agent methyl methanesulphonate (MMS, 44 µg/mL for the micronucleus assay and 22 µg/mL for the comet assay) as an inducer of micronuclei and DNA damage. RESULTS: The results showed that SL was cytotoxic at concentrations up to 64 µg/mL. No significant differences in the rate of chromosome or DNA damage were observed between cultures treated with SL and the control group. In addition, the frequencies of micronuclei and DNA damage induced by MMS were significantly reduced after treatment with SL. The damage reduction percentage ranged from 68.1% to 79.2% and 12.1% to 16.5% for micronucleus and comet assays, respectively. DISCUSSION AND CONCLUSION: SL exerted no genotoxic effect and exhibited chemopreventive activity against both genomic and chromosome damage induced by MMS.
Assuntos
Extratos Vegetais/farmacologia , Solanum , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cricetinae , Cricetulus , Dano ao DNA , Metanossulfonato de Metila/toxicidade , Testes para Micronúcleos , Testes de Mutagenicidade , Extratos Vegetais/toxicidadeRESUMO
Sea urchins are noted for the absence of neoplastic disease and represent a novel model to investigate cellular and systemic cancer protection mechanisms. Following intracoelomic injection of the DNA alkylating agent methyl methanesulfonate, DNA damage was detected in sea urchin cells and tissues (coelomocytes, muscle, oesophagus, ampullae and gonad) by the alkaline unwinding, fast micromethod. Gene expression analyses of the coelomocytes indicated upregulation of innate immune markers, including genes involved in NF-κB signalling. Results suggest that activation of the innate immune system following DNA damage may contribute to the naturally occurring resistance to neoplastic disease observed in sea urchins.
Assuntos
Dano ao DNA , Expressão Gênica/efeitos dos fármacos , Lytechinus/efeitos dos fármacos , Metanossulfonato de Metila/toxicidade , Mutagênicos/toxicidade , Animais , Sistema Imunitário/efeitos dos fármacos , Lytechinus/genéticaRESUMO
Dragon ́s blood root (Jatropha dioica) underwent a phytochemical screening showing the presence of flavonoids and terpenes responsible for the antioxidant potential observed in DPPH model for the decoction, aqueous and methanolic extracts. The chemoprotective effect of the root decoction was evaluated in liver, kidney and bone marrow cells of mice using the comet assay. Mutagens were administered via IP: cyclophosphamide (CCF) 50 mg/kg, daunorubicin (DAU) 10 mg/kg, and metyl metanesulfonate (MMS) 40 mg/kg, were co-administered with three doses of decoction 3.72 ml/kg, 10.71 ml/kg, and 21.42 ml/kg orally. Animals were sacrificed at 3, 9, 15 and 21 h after inoculation. The chemoprotective effect decreased DNA breaks at 3 hours in all organs, and longer against CCF and DAU, this effect probably being related to the antioxidant capacity of the decoction.
La raíz de Sangre de Drago (Jatropha dioica) se sometió a un tamizaje fitoquímico destacando la presencia de flavonoides y terpenos, posibles responsables del efecto antioxidante observado en el modelo de DPPH para la decocción, extracto acuoso y metanólico de la raíz. El efecto quimioprotector de la decocción, se evaluó en células hepáticas, renales y de médula ósea de ratón, mediante el ensayo cometa. Los mutágenos administrados vía I.P.: ciclofosfamida (CCF) 50 mg/kg, daunorrubicina (DAU) 10 mg/kg y metilmetanosulfonato (MMS) 40 mg/kg, se co-administraron con tres dosis de decocción 3,72 ml/kg, 10,71 ml/kg y 21,42 ml/kg, vía oral. Los animales fueron sacrificados a las 3, 9, 15 y 21 h posteriores a la aplicación. El efecto quimioprotector disminuyó las rupturas del DNA a las 3 horas en todos los órganos con los tres mutágenos, y permaneció por más tiempo frente a CCF y DAU, dicho efecto está relacionado con la capacidad antioxidante de la decocción.
Assuntos
Animais , Camundongos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Genotoxicidade/prevenção & controle , Jatropha/química , Substâncias Protetoras/farmacologia , Compostos de Bifenilo , Ensaio Cometa , Ciclofosfamida/toxicidade , Daunorrubicina/toxicidade , Metanossulfonato de Metila/toxicidade , PicratosRESUMO
Salvia officinalis (sage) is a perennial woody subshrub native to the Mediterranean region that is commonly used as a condiment and as an anti-inflammatory, antioxidant and antimicrobial agent due to its biological activities. Manool is the most abundant micro-metabolite found in Salvia officinalis essential oils and extracts. We therefore decided to evaluate the cytotoxic, genotoxic and antigenotoxic potential of manool in Chinese hamster lung fibroblasts (V79) and human hepatoma cells (HepG2). Cytotoxicity was assessed by the colony-forming assay in V79 cells and toxic effects were observed at concentrations of up to 8.0 µg/mL. The micronucleus test was used to evaluate the genotoxicity and antigenotoxicity of manool in V79 and HepG2 cells at concentrations of 0.5-6.0 µg/mL and 0.5-8.0 µg/mL, respectively. For evaluation of antigenotoxicity, the concentrations of manool were combined with methyl methanesulfonate (MMS, 44 µg/mL). The results showed a significant increase in the frequency of micronuclei in cultures of both cell lines treated with the highest concentration tested, demonstrating a genotoxic effect. On the other hand, manool exhibited a protective effect against chromosome damage induced by MMS in HepG2 cells, but not in V79 cells. These data suggest that some manool metabolite may be responsible for the antigenotoxic effect observed in HepG2 cells.
Assuntos
Dano ao DNA/efeitos dos fármacos , Diterpenos/farmacologia , Metanossulfonato de Metila/toxicidade , Extratos Vegetais/farmacologia , Salvia officinalis/química , Animais , Antioxidantes/farmacologia , Linhagem Celular , Cricetinae , Cricetulus , Células Hep G2 , Humanos , Testes para MicronúcleosRESUMO
The search for substances able to inhibit and/or diminish the effects of genotoxic and mutagenic substances has been the target of several investigations performed in recent times. Hymenoptera venoms constitute a considerable source of substances with pharmacological potential. The present study aimed to evaluate the cytotoxic, genotoxic and anti-genotoxic, mutagenic and anti-mutagenic potentials of Apis mellifera venom in HepG2 cells. In this evaluation, the MTT test was applied to determine the most appropriate concentrations for the genotoxicity and mutagenicity tests. It was verified that the concentrations of 0.1, 0.05 and 0.01µg/mL were not cytotoxic, hence these concentrations were used in the experiments. For the evaluation of the genotoxic and mutagenic potential of the bee venom the comet assay and the micronucleus test were applied, respectively. The concentrations mentioned above presented both genotoxic and mutagenic potential for HepG2 cells and it was necessary to test lower concentrations of the venom (10pg/mL, 1pg/mL and 0.1pg/mL) for the anti-genotoxicity and anti-mutagenicity tests, which were performed subjecting the cells to the action of MMS (methyl methanesulfonate) in order to verify the ability of the venom to inhibit or diminish the action of this compound, which has a recognized action on the genetic material. Pre-, post-treatment and simultaneous treatment with and without incubation with the venom were performed. It was observed that the lowest three concentrations tested did not present any anti-genotoxic and anti-mutagenic activity on the cells. The use of bee venom for pharmacological purposes in treatments such as cancer must be done with extreme caution, since it was observed that even at very low concentrations the venom can induce genotoxicity and mutagenicity in human cells, as was verified for the HepG2 cells.
Assuntos
Antimutagênicos/farmacologia , Venenos de Abelha/farmacologia , Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Animais , Antimutagênicos/toxicidade , Venenos de Abelha/toxicidade , Abelhas , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Metanossulfonato de Metila/análogos & derivados , Metanossulfonato de Metila/toxicidade , Testes de Mutagenicidade , Mutagênicos/toxicidadeRESUMO
Usnic acid is one of the most common and abundant metabolites found in various lichen genera, which are important sources of biologically active compounds. The aim of this study was to evaluate the genotoxic and antigenotoxic potential of (+)-usnic acid (UA) by the micronucleus and comet assays in V79 cell cultures and Swiss mice. For assessment of genotoxicity, V79 cells were treated with 15, 30, 60, and 120µg/mL UA, established based on clonogenic efficiency cytotoxic assay. Swiss mice were treated with UA doses of 25, 50, 100, and 200mg/kg body weight. The same concentrations of UA were combined with methyl methanesulfonate (MMS) for evaluation of antigenotoxicity. The in vitro results demonstrated that UA induced DNA damage at concentrations of 60 and 120µg/mL in the comet assay. However, no genotoxic effect was observed in the micronucleus test using V79 cells at the concentrations tested. No genotoxic effects were observed for the different UA treatments in in vivo test system. Combined administration of UA and MMS significantly reduced the frequencies of micronuclei and DNA damage in vitro and in vivo when compared to treatment with MMS alone. Although the mechanisms underlying the protective effect of UA are not completely understood, the antioxidant activity of this metabolite may explain its protective effect against MMS-induced genotoxicity.
Assuntos
Antimutagênicos/farmacologia , Benzofuranos/farmacologia , Benzofuranos/toxicidade , Ensaio Cometa/métodos , Testes para Micronúcleos/métodos , Animais , Antioxidantes/farmacologia , Medula Óssea/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Masculino , Metanossulfonato de Metila/toxicidade , CamundongosRESUMO
Styrax camporum Pohl is a tall shrub or a tree with small white flowers, which grows in the states of São Paulo and Minas Gerais and is popularly used for the treatment of gastroduodenal diseases. Considering this last fact, the aim of this study was to evaluate the genotoxic potential of S. camporum hydroalcoholic extract and its influence on genotoxicity induced by doxorubicin and methyl methanesulfonate in Swiss mice using the micronucleus and comet assays, respectively. The animals were treated by gavage with different doses of the extract (250, 500, and 1000 mg/kg body weight). For antigenotoxicity assessment, different doses of the S. camporum extract were administered simultaneously with doxorubicin (micronucleus test; 15 mg/kg) and methanesulfonate (comet assay; 40 mg/kg). The results showed that the S. camporum extract itself was not genotoxic in the mouse micronucleus or comet assay. The number of micronucleated polychromatic erythrocytes was significantly lower in animals treated with the S. camporum extract and doxorubicin when compared to animals treated only with doxorubicin. In the comet assay, the S. camporum extract, at the doses tested, significantly reduced the extent of DNA damage in liver cells induced by methanesulfonate. The putative activity of the active compounds of S. camporum extract may explain the effect of this plant on genotoxicity induced by doxorubicin and methanesulfonate.
Assuntos
Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/antagonistas & inibidores , Metanossulfonato de Metila/antagonistas & inibidores , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Extratos Vegetais/farmacologia , Styrax/química , Animais , Ensaio Cometa , Relação Dose-Resposta a Droga , Doxorrubicina/toxicidade , Lipossomos , Masculino , Metanossulfonato de Metila/toxicidade , Camundongos , Testes para Micronúcleos , Caules de Planta/químicaRESUMO
The pimarane-type diterpene, pimaradienoic acid (PA), is known for its diverse biological properties such as antimicrobial, anti-inflammatory and trypanocidal. A preliminary study was undertaken to investigate in vitro the free radical-scavenging potential of PA. In addition, the genotoxic potential of PA and its ability to modulate genotoxicity induced by doxorubicin (DXR) and methyl methanesulfonate (MMS) were studied in Chinese hamster lung fibroblasts (V79 cells) and in male Swiss mice using the comet and micronucleus assays. The DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay showed that PA exerted no antioxidant activity when compared to quercetin. The colony-forming assay using V79 cells showed that PA was cytotoxic at concentrations >5.0µg/mL. Therefore, concentrations of 0.625, 1.25, 2.5, and 5.0µg/mL were used for evaluation of the genotoxic and antigenotoxic potential of PA in V79 cells. For genotoxic and antigenotoxic assessment in Swiss mice, three PA doses were tested (20, 40, and 80mg/kg body weight) based on the solubility limit of the diterpene in dimethylsulfoxide and water. The in vitro results demonstrated that PA induced DNA damage at concentrations of 2.5 and 5.0µg/mL in the comet assay. However, no genotoxic effect was observed in the micronucleus test using V79 cells. In the in vivo evaluation of genotoxicity, a significant increase in the frequency of DNA damage was observed in hepatocytes of animals treated with the highest PA dose (80mg/kg) when compared to the control group, but this difference was not seen in the micronucleus test. Furthermore, PA significantly reduced the frequency of DXR- and MMS-induced micronuclei and extent of DNA damage in in vitro and in vivo test systems.
Assuntos
Dano ao DNA/efeitos dos fármacos , Diterpenos/toxicidade , Mutagênicos/toxicidade , Animais , Linhagem Celular , Ensaio Cometa , Cricetinae , Cricetulus , Diterpenos/administração & dosagem , Diterpenos/química , Doxorrubicina/toxicidade , Fibroblastos/efeitos dos fármacos , Masculino , Metanossulfonato de Metila/toxicidade , Camundongos , Testes para MicronúcleosRESUMO
Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H(2)O(2)), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD(50) values determined for coelomocytes after 24h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H(2)O(2), MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.
Assuntos
Ouriços-do-Mar/efeitos dos fármacos , Ouriços-do-Mar/efeitos da radiação , Raios Ultravioleta , Poluentes Químicos da Água/toxicidade , Animais , Aplysia/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Hemócitos/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Dose Letal Mediana , Metanossulfonato de Metila/toxicidade , Palinuridae/citologia , Palinuridae/efeitos dos fármacos , Ouriços-do-Mar/citologiaRESUMO
Baccharin is one of the major chemical compounds isolated from the aerial parts of Baccharis dracunculifolia DC (Asteraceae), a native plant of South America and the most important botanical source of the Brazilian green propolis that has been used in alternative medicine to treat inflammation, liver disorders, and stomach ulcers. The present study was carried out in V79 cells to determine the possible genotoxic and antigenotoxic activities of baccharin utilizing comet and micronucleus assays, where 2 known mutagenic agents with different mechanisms of DNA damage were used as positive controls. The V79 cells were treated with concentrations of baccharin (0.25, 0.5, 1.0, and 2.0 µg/mL) and for to investigate the antigenotoxicity these concentrations were associated with methyl methanesulfonate (MMS; 200 µM-comet assay and 400 µM-micronucleus assay) or hydrogen peroxide (H(2)O(2;) 50 µM-comet assay and 100 µM-micronucleus assay). Statistically significant differences in the rate of DNA damage were observed in cultures treated with the highest concentration of baccharin when compared to the control group, but this difference was not found in the micronucleus assay. The results also showed that the frequencies of DNA damage and micronuclei induced by MMS and H(2)O(2) were significantly reduced after treatment with baccharin. The baccharin showed a chemoprevention effect and can be the chemical compound responsible for the antigenotoxicity also demonstrated by the B. dracunculifolia. The antioxidant potential of baccharin may be related to its chemoprevention activity induced against both genomic and chromosomal damages.
Assuntos
Baccharis/química , Dano ao DNA/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Metanossulfonato de Metila/toxicidade , Extratos Vegetais/farmacologia , Tricotecenos/farmacologia , Animais , Antioxidantes/farmacologia , Brasil , Linhagem Celular , Ensaio Cometa , Cricetinae , Testes para Micronúcleos , Mutagênicos/toxicidadeRESUMO
The aim of this study was to evaluate alkylation induced genotoxicity as a result of DNA repair deficiency during 4-nitroquinoline 1-oxide (4NQO)-induced rat tonguecarcinogenesis by means of single cell gel (comet)assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks.Ten animals were used as negative control. Blood samples and oral mucosa cells collected from all animals were divided into two aliquots of 20 lL each to study basal DNA damage and DNA damage due to genotoxin sensitivity.The first aliquot was processed immediately for comet assay to assess basal DNA damage. The second aliquot was treated with a known genotoxin, methylmetanesulfonate.Significantly greater DNA damage was noticed to oral mucosa cells from 4, and 12 weeks posttreatment.Peripheral blood cells did show statistically significant differences (P\0.05) after 20 weeks-group(squamous cell carcinoma). In conclusion, alkylation induced genotoxicity as a result of DNA repair deficiency is present in oral mucosa cells following oral experimental carcinogenesis.
Assuntos
Carcinógenos/toxicidade , Carcinoma de Células Escamosas/metabolismo , Reparo do DNA/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , Neoplasias da Língua/metabolismo , 4-Nitroquinolina-1-Óxido/toxicidade , Administração Oral , Alquilação , Animais , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/genética , Ensaio Cometa , DNA/genética , DNA/metabolismo , Dano ao DNA , Água Potável , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Metanossulfonato de Metila/toxicidade , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Ratos , Ratos Wistar , Fatores de Tempo , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/genéticaRESUMO
The effect of culinary-medicinal Royal Sun Agaricus (Agaricus brasiliensis) hot water extract on methyl methane sulfonate (MMS) induced mutagenicity/genotoxity in Drosophila melanogaster was studied using a quick and broadly applicable in vivo assay, i.e., the wing somatic mutation and recombination test. We used 2nd instar larvae, trans-heterozygous for the third chromosome recessive markers, i.e., multiple wing hairs (mvh) and flare-3 [flr (3)], and fed them for 24 h with the aqueous extract of A. brasiliensis. For antigenotoxicity studies a 24-h pretreatment with the extract was done, followed by a 48-h treatment of the then 3rd instar larvae with MMS. The frequency of mutations of the wing blade changes (i.e., of the number of wing spots of different sizes) induced in somatic cells was determined as a parameter of genetic changes of the wing imaginal discs. The results showed that A. brasiliensis extract did not cause any genotoxic or mutagenic effects. No antigenotoxic and/or protective effect against the induction of mutations by MMS was observed. Instead, a possible enhanced mitotic recombination frequency by MMS was seen after pretreatment of the larvae with A. brasiliensis extract. Possible mechanisms of action are discussed.
Assuntos
Agaricus/química , Antimutagênicos/farmacologia , Fatores Biológicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Alimento Funcional/análise , Metanossulfonato de Metila/toxicidade , Mutagênicos/toxicidade , Animais , Antimutagênicos/análise , Antimutagênicos/isolamento & purificação , Fatores Biológicos/análise , Fatores Biológicos/isolamento & purificação , Drosophila melanogaster/crescimento & desenvolvimento , Testes de Mutagenicidade , Asas de Animais/efeitos dos fármacos , Asas de Animais/crescimento & desenvolvimentoRESUMO
Baccharin (3-prenyl-4-(dihydrocinnamoyloxy)cinnamic acid) is an important chemical compound isolated from the aerial parts of Baccharis dracunculifolia DC (Asteraceae), a native plant of South America, and the most important plant source of Brazilian green propolis. The present study was designed to investigate the ability of baccharin to modulate the genotoxic effects induced by doxorubicin and methyl methanesulphonate in male Swiss mice using the micronucleus and comet assays, respectively. The different doses of baccharin [0.12, 0.24 and 0.48 mg/kg body-weight (b.w.)] were administered simultaneously to doxorubicin (micronucleus test; 15 mg/kg b.w.) and to methyl methanesulphonate (comet assay; 40 mg/kg b.w.). The results showed a significant decrease in the frequency of micronucleated polychromatic erythrocytes in animals treated with baccharin and doxorubicin compared to animals that received only doxorubicin. This reduction ranged from 39.8% to 50.7% in the micronucleus test. The extent of DNA damage in liver cells was significantly lower in animals treated with different concentrations of baccharin combined with methyl methanesulphonate in comparison with the damage observed for animals treated only with methyl methanesulphonate. These differences resulted in a significant reduction in the extent of DNA damage, which ranged from 47.8% to 60.6%.
Assuntos
Antimutagênicos/farmacologia , Doxorrubicina/toxicidade , Metanossulfonato de Metila/toxicidade , Tricotecenos/farmacologia , Animais , Antibióticos Antineoplásicos/toxicidade , Antimutagênicos/administração & dosagem , Antimutagênicos/isolamento & purificação , Antineoplásicos Alquilantes/toxicidade , Baccharis/química , Brasil , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Testes para Micronúcleos , Mutagênicos/toxicidade , Componentes Aéreos da Planta , Tricotecenos/administração & dosagem , Tricotecenos/isolamento & purificaçãoRESUMO
Artepillin C (3,5-diprenyl-p-coumaric acid), a major compound found in Brazilian green propolis and Baccharis dracunculifolia, shows anti-inflammatory, antibacterial, antiviral, antioxidant and antitumoral activities, among others. The aim of this study was to evaluate the genotoxic potential of artepillin C and its ability to prevent the chemically induced chromosome breakage or loss and the primary DNA damage using the micronucleus and comet assays in male Swiss mice, respectively. The animals were treated by gavage with different doses of artepillin C (0.4, 0.8 and 1.6 mg kg(-1) b.w.). For the antigenotoxicity assays, the different doses of artepillin C were administered simultaneously to doxorubicin (DXR; micronucleus test; 15 mg kg(-1) b.w.) and to methyl methanesulfonate (MMS; comet assay; 40 mg kg(-1) b.w.). The results showed that artepillin C itself was not genotoxic in the mouse micronucleus and comet assays. In the animals treated with artepillin C and DXR, the number of micronucleated reticulocytes was significantly lower in comparison with the animals treated only with DXR. Regarding antigenotoxicity, artepillin C at the tested doses significantly reduced the extent of DNA damage in liver cells induced by MMS.
Assuntos
Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Testes para Micronúcleos/métodos , Fenilpropionatos/farmacologia , Extratos Vegetais/farmacologia , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Baccharis/química , Quebra Cromossômica/efeitos dos fármacos , Doxorrubicina/toxicidade , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Metanossulfonato de Metila/toxicidade , Camundongos , Mutagênicos/toxicidade , Reticulócitos/efeitos dos fármacosRESUMO
The flavonoid quercetin and its derivative rutin were investigated for genotoxicity/antigenotoxicity activity in human hepatoma HepG2 cells using the comet assay. The extract cytotoxicity was evaluated using the trypan blue exclusion dye method with quercetin and rutin concentrations ranging from 0.1 to 200.0 µg/mL of culture medium. Three minor non-cytotoxic concentrations were chosen to evaluate the genotoxicity and antigenotoxicity of the flavonoids (0.1, 1.0 and 5.0 µg/mL) through comet assay. The cultures were treated with three different concentrations of rutin or quercetin (genotoxicity) or their association with Aflatoxin B1 (AFB1), methyl methanesulfonate (MMS) or doxorubicin (DXR) (antigenotoxicity test) in three protocols: pre-treatment, simultaneous treatment and post-treatment. The cell cultures were also treated with 1% DMSO (control group), AFB1, MMS and DXR (positive-control). Statistical analyses were performed using ANOVA and Dunnett's test (p ≤ 0.05). Quercetin at concentrations higher than 10.0 µg/mL or rutin higher than 50.0 µg/mL exhibited a cytotoxic effect on the cells, showing that quercetin is more cytotoxic than rutin. Furthermore, neither compound was able to induce genotoxicity in the concentrations evaluated. On the other hand, both flavonoids reduced DNA damage induced by AFB1, MMS and DXR in all treatment protocols.