RESUMO
Proanthocyanidins (PAs), also known as condensed tannins, are naturally occurring oligomers and polymers of flavan-3-ol monomer units widely found in the leaves, flowers, fruits, seeds, nuts and barks of many plants. Grape seed proanthocyanidins (GSPs) have been used as nutritional supplements, as antioxidants, in preventing atherosclerosis and cardiovascular diseases, and for dislipidemy treatment. The anthracycline antibiotic adriamycin (Doxorubicin, DXR) is a cancer chemotherapeutic agent that interferes with the topoisomerase II enzyme and generates free radicals. In the present study, GSPs (1.680, 3.375, or 6.750 mg/mL) alone were examined for genotoxicity, and combined with DXR (0.125 mg/mL) for antigenotoxicity, using the standard (ST) and high bioactivation (HB) versions of the wing somatic mutation and recombination test in Drosophila melanogaster. The results observed in both crosses were rather similar. GSPs themselves did not show genotoxicity at the doses used. GSPs suppressed the DNA damage induced by DXR in a dose-dependent manner. Comparison of the frequencies of wing spots in the marker-heterozygous (MH) flies and balancer-heterozygous (BH) flies from both crosses, indicated that induced recombination was the major response for the treatments with DXR alone. The co-treatments demonstrated that GSPs have some anti-mutagenic activity; however, anti-recombinagenic activity was the major response.
Assuntos
Antibióticos Antineoplásicos/antagonistas & inibidores , Antibióticos Antineoplásicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/antagonistas & inibidores , Doxorrubicina/toxicidade , Proantocianidinas/farmacologia , Vitis/química , Animais , Relação Dose-Resposta a Droga , Drosophila melanogaster , Comportamento Alimentar/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Larva , Testes de Mutagenicidade , Proantocianidinas/química , Sementes/química , Análise de Sobrevida , Asas de Animais/anatomia & histologiaRESUMO
The wing Somatic Mutation and Recombination Test (SMART) in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone) and ß-lapachone (quinone) are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II) or inducing other enzymes dependent on NAD(P)H:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST) version, which has normal levels of cytochrome P450 (CYP) enzymes, to check the direct action of this compound, and in the high bioactivation (HB) version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10%, 20% or 40% w/w). It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR). In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0%) on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture.
RESUMO
The wing Somatic Mutation and Recombination Test (SMART) in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone) and β-lapachone (quinone) are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II) or inducing other enzymes dependent on NAD(P)H:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST) version, which has normal levels of cytochrome P450 (CYP) enzymes, to check the direct action of this compound, and in the high bioactivation (HB) version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10 percent, 20 percent or 40 percent w/w). It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR). In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0 percent) on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture.
RESUMO
Panax ginseng is one of the most widely prescribed herbal medicines for the treatment of cancer, diabetes, chronic inflammation, and neurodegenerative and cardiovascular diseases. Since the use of alternative medicines in combination with conventional therapy may increase the risk of unwanted interactions, we investigated the possible genotoxicity of a water-soluble form of the dry root of P. ginseng (2.5, 5.0 or 10.0 mg/mL) and its ability to protect against the genotoxicity of doxorubicin (DOX; 0.125 mg/mL) by using the Drosophila melanogaster wing somatic mutation and recombination test (SMART) with standard and high-bioactivation crosses of flies. Panax ginseng was not genotoxic at the concentrations tested, whereas DOX-induced genotoxicity in marker-heterozygous flies resulted mainly from mitotic recombination. At low concentrations, P. ginseng had antirecombinogenic activity that was independent of the concentration of extract used. Recombination events may promote cancer, but little is known about the ability of P. ginseng to inhibit such recombination or modulate DNA repair mechanisms.
Assuntos
Animais , Doxorrubicina/toxicidade , Drosophila melanogaster/genética , Panax , Drosophila melanogaster , Fitoterapia , Plantas Medicinais , Asas de AnimaisRESUMO
Triasulfuron (TS) is a widely used sulfonylurea herbicide which inhibits the acetolactate synthase in broad-leaf weeds and in some wheat crop grasses (Triticum aestivum L.). Residues can be found in soil and superficial water with high toxicity to primary producers. In cereals, TS metabolism depends on cytochromes P450 (CYPs), the age of seedlings and the interaction with compounds. The genotoxicity of TS was demonstrated in the wing spot test of Drosophila melanogaster, an in vivo assay based on the loss of heterozygosity of the mwh and flr markers in the wing imaginal disk cells of larvae fed with chemical agents. Chronic treatments with analytical grade TS, commercial formulation TS (Amber) 75WG) (0.5mg/mL) and commercial formulation bentazon (Basagran) 480) (0.24mg/mL) were performed with three-day-old larvae of the standard (ST) and the high bioactivation (HB) crosses with regulated and high constitutive levels of CYPs, respectively. To demonstrate the effect of winter wheat metabolism on TS genotoxicity, T. aestivum L. seedlings were immersed for 4h in these herbicides, and aqueous extracts (AEs) of the roots were prepared to expose the larvae. TS and Amber 75WG produced similar genotoxic effects in both crosses. Wheat metabolism modulated the genotoxicity because the AEs yielded statistically significant lower spot frequencies in the HB cross than in the ST cross. Differences between the two crosses of the wing spot test in D. melanogaster must be related to CYPs levels. Basagran 480 was genotoxic only in the HB cross, and wheat metabolism did not modulate its genotoxicity.
Assuntos
Perda de Heterozigosidade/efeitos dos fármacos , Testes de Mutagenicidade , Mutagênicos/análise , Plântula , Compostos de Sulfonilureia/análise , Triticum , Asas de Animais , Animais , Benzotiadiazinas/análise , Benzotiadiazinas/metabolismo , Cruzamentos Genéticos , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Marcadores Genéticos , Herbicidas/análise , Herbicidas/metabolismo , Larva/genética , Larva/metabolismo , Testes de Mutagenicidade/métodos , Mutagênicos/metabolismo , Proteínas de Plantas/metabolismo , Plântula/enzimologia , Compostos de Sulfonilureia/metabolismo , Fatores de Tempo , Triticum/enzimologiaRESUMO
In the present study, five analogous herbicides, namely Imazapyr (IMZR), Imazapic (IMZC), Imazethapyr (IMZT), Imazamox (IMZX) and Imazaquin (IMZQ), were evaluated for genotoxicity (mutagenic and recombinagenic activity) in the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. They are classified as imidazolinone (IMI) herbicides and their mode of action is to inhibit acetohydroxyacid synthase (AHAS), an enzyme involved in the biosynthesis of the amino acids leucine, isoleucine and valine. Two crosses were used: the standard (ST) cross and the high bioactivation (HB) cross. The latter is characterized by high levels of cytochrome P450 conferring increased sensitivity to promutagens and procarcinogens. Three-day-old larvae were exposed by chronic feeding (48 h) to four different concentrations of these herbicides (2.5, 5.0, 10.0 or 20.0 mM). For the evaluation of genotoxic effects, the frequencies of spots per individual in the treated series were compared to the concurrent negative control series (ultrapure water). Imazapyr, Imazapic and Imazethapyr gave negative results with both crosses of the wing spot test. In the ST cross, Imazamox showed positive results only for large single spots (20.0 mM IMZX) and weak positive results for total spots (10.0 and 20.0 mM IMZX), while Imazaquin showed positive results only for large single spots (5.0 and 20.0mM IMZQ) and a weak positive result for total spots (20.0 mM IMZQ). These positive results are mainly due to induced recombination and to a minor extent to mutations. In the HB cross, only Imazamox (5.0 mM IMZX) showed a weak positive result for small single spots. The positive control urethane, a promutagen, caused an increase in the number of all types of spots in both crosses. In conclusion, the results of chronic treatments performed at high doses (toxicity was observed at higher doses) shows the existence of a genotoxic risk for IMZX and IMZQ exposure under these experimental conditions, and indicate the need for further research to delineate the exact mechanisms involved.
Assuntos
Hyptis/química , Mutagênicos , Fenantrenos/toxicidade , Abietanos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Cricetinae , Cricetulus , Dano ao DNA/efeitos dos fármacos , Testes para Micronúcleos , Testes de Mutagenicidade , Fenantrenos/química , Raízes de Plantas/químicaRESUMO
A Mandevilla velutina crude extract was investigated using the mouse micronucleus test (MNT) and the Drosophila melanogaster somatic mutation and recombination test (SMART) using standard (ST) and high bioactivation (HB) crosses. The MNT used 10 mg, 20 mg or 40 mg per 100 g of body weight (bw) of extract with and without 0.2 mg per 100 g bw peritoneal cyclophosphamide. There was no genotoxicity in the negative control or extract only groups and, compared to the cyclophosphamide control, there was a significant reduction in micronucleated polychromatic erythrocytes in all the groups given extract plus cyclophosphamide. For SMART larvae were fed 5 or 10 mg mL-1 of extract for seven days with and without 0.89 mg mL-1 of urethane given on day seven. The ST and HB flies showed no significant differences in spots between the negative control and the extract only groups. The number of urethane-induced spots was reduced by the highest concentration of extract for the ST flies and by both concentrations of extract for the HB flies. The results suggest that M. velutina extract is not genotoxic but is antigenotoxic.
RESUMO
The Drosophila melanogaster somatic mutation and recombination test (SMART) was used to assess the genotoxicity of surface (S) and bottom (B) water and sediment samples collected from Sites 1 and 2 on the Japaratuba River (Sergipe, Brazil), an area impacted by a petrochemical industrial complex that indirectly discharges treated effluent (produced water) into the river. The genotoxicity tests were performed in standard (ST) cross and high bioactivation (HB) cross flies and were conducted on samples taken in March (dry season) and in July (rainy season) of 2003. Mutant spot frequencies found in treatments with unprocessed water and sediment samples from the test sites were compared with the frequencies observed for similar samples taken from a clean reference site (the Jacarecica River in Sergipe, Brazil) and those of negative (ultrapure water) controls. While samples from the Japaratuba River generally produced greater responses than those from the Jacarecica River, positive responses were detected for both the test and reference site samples. All the water samples collected in March 2003 were genotoxic. In July 2003, the positive responses were restricted to water samples collected from Sites 1 B and 2 S in the ST cross. The genotoxicity of the water samples was due to mitotic recombination, and the samples produced similar genotoxic responses in ST and HB flies. The spot frequencies found in the July water samples were considerably lower than those for the March water samples, suggesting a seasonal effect. The only sediment samples that were genotoxic were from Site 1 (March and July) and from the Jacarecica River (March). The genotoxins in these samples produced both somatic mutation (limited to the Site 1 sample in HB flies) and recombination. The results of this study indicate that samples from both the Japaratuba and Jacarecica Rivers were genotoxic, with the most consistently positive responses detected with Site 1 samples, the site closest to the putative pollution source.
Assuntos
Drosophila/efeitos dos fármacos , Mutagênicos/toxicidade , Rios/química , Poluentes Químicos da Água/toxicidade , Asas de Animais/efeitos dos fármacos , Animais , Brasil , Drosophila/anatomia & histologia , Monitoramento Ambiental/métodos , Poluição Ambiental/efeitos adversos , Testes de Mutagenicidade , Asas de Animais/anatomia & histologiaRESUMO
Neurocysticercosis, the most common parasitic disease of the central nervous system, is caused by cysticerci of the helminth Taenia solium, which is prevalent in developing countries and is reemerging in affluent societies. This helminth is associated with brain tumors and hematological malignancies in humans. In the present study, we analyzed the genotoxicity of vesicular fluid (VF) and a saline extract (SE) of T. solium metacestodes in the Drosophila melanogaster wing somatic mutation and recombination test (SMART). Third-instar larvae derived from standard and high bioactivation crosses were treated for approximately 48 hr with 12.5, 25.0, and 50.0 microg/ml of VF and SE of T. solium metacestodes. Negative (phosphate buffered saline) and positive (10 mM urethane) controls were also included. The results showed that the two test compounds were genotoxic in both crosses of Drosophila. Nevertheless, further research is needed to determine the genotoxic potential of specific compounds present in VF and SE and their role in the development of cancer.
Assuntos
Drosophila melanogaster/efeitos dos fármacos , Mutagênicos/toxicidade , Taenia solium/química , Asas de Animais/efeitos dos fármacos , Animais , Drosophila melanogaster/genética , Feminino , Masculino , Testes de Mutagenicidade , Mutação , Recombinação Genética , Cloreto de Sódio/químicaRESUMO
Stryphnodendron adstringens (Mart.) Coville, a medicinal plant that grows in the "cerrados" (a savanna ecosystem) of Brazil, popularly known as "Barbatimão," is an important source of tannins (polyphenols). In Brazil, it is used in industry (mainly as vegetable tanning) and also in traditional medicine for the treatment of various diseases. In the present study, a phytotherapeutic extract from S. adstringens stem bark was evaluated for mutagenic and recombinagenic effects using the wing spot test of Drosophila melanogaster (somatic mutation and recombination test, SMART), and for chromosome damage in germ cells using the Drosophila sex-chromosome loss test (ring-X loss). For SMART, the standard as well as the high bioactivation fly crosses were used; the latter cross is characterized by a high sensitivity to promutagens and procarcinogens. Third-instar larvae from these two crosses were treated for 48 hr with different concentrations (66%, 75%, and 100%) of the phytotherapeutic extract. The wings of the emerging adults were analyzed for the occurrence of different types of mutant spots. No statistically significant differences in spot frequencies between controls and treated series were observed. For the ring-X loss test, adult males were fed with the same concentrations of the extract as in the wing spot test. No statistically significant increases in ring-X losses were observed. The results of our experiments suggest that the phytotherapeutic extract from S. adstringens stem bark is not genotoxic in somatic and germ cells of D. melanogaster.