RESUMO
In the present study, we injected pregnant mice at Day 7 of gestation with cadmium chloride (CC) (1.5 mg/kg) intraperitoneally and determined its effect on the frequency of fetal malformations at Day 17 of pregnancy. On the same day, we also determined the level of micronucleated polychromatic erythrocytes (MNPEs) and of micronucleated normochromatic erythrocytes (MNNEs) in blood cells of both the mothers and their fetuses. A significant increase in the number of malformations was found, mainly exencephaly, micrognathia, ablephary, microphthalmia, and clubfoot, as well as a significant increase in the amount of MNPEs and MNNEs. In addition, pregnant mice were administered grapefruit juice (GJ) orally from Days 0 to 17 of the experiment (from 200 to 800 µL/g) to evaluate the potential of the juice in preventing the damage induced by CC. We found a dose-dependent decrease in the number of visceral and skeletal malformations, as well as in the number of MNPEs and MNNEs, in both the mothers and their fetuses. Furthermore, we determined the level of DNA oxidation by measuring levels of the adduct 8-hydroxy-2'-deoxyguanosine, and we found a significant increase in such level induced by CC; in contrast, there was a significant decrease when we added GJ. Therefore, the observed teratogenic and genotoxic protection can probably be related with the antioxidant potential of GJ.
Assuntos
Bebidas , Cádmio/toxicidade , Citrus paradisi/química , Dano ao DNA/efeitos dos fármacos , Feto/efeitos dos fármacos , Teratogênicos/toxicidade , Animais , Antioxidantes/farmacologia , Cloreto de Cádmio/administração & dosagem , Cloreto de Cádmio/toxicidade , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Mutagênicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , GravidezRESUMO
The chemical alpha-asarone is an important active substance of the Acori graminei rhizome (AGR). It has pharmacological effects that include antihyperlipidemic, antiinflammatory, and antioxidant activity. Our aim was to study the effects alpha-asarone on nitric oxide (NO) levels in the hippocampus and temporal cortex of the rat after injection of the fraction 25-35 from amyloid-beta (Abeta((25-35))). In addition we examined the working spatial memory in an eight-arm radial maze. Our results showed a significant increase of nitrites in the hippocampus and temporal cortex of Abeta((25-35))-treated rats. Other evidence of neuronal damage was the expression of a glial-fibrillar-acid protein and a silver staining. There were impairments in the spatial memory evaluated in the eight-arm radial maze. We wanted to determine whether alpha-asarone improves the memory correlated with NO overproduction and neuronal damage caused by the injection of Abeta((25-35)) into rats. Then animals received a 16-day treatment of alpha-asarone before the Abeta((25-35)) injection. Our results show a significant decrease of nitrite levels in the hippocampus and temporal cortex, without astrocytosis and silver-staining cells, which correlates with memory improvement in the alpha-asarone-treated group. Our results suggest that alpha-asarone may protect neurons against Abeta((25-35))-caused neurotoxicity by inhibiting the effects of NO overproduction in the hippocampus and temporal cortex.
Assuntos
Anisóis/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/metabolismo , Administração Oral , Derivados de Alilbenzenos , Peptídeos beta-Amiloides , Animais , Anisóis/administração & dosagem , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Masculino , Memória/efeitos dos fármacos , Microinjeções , Fármacos Neuroprotetores/administração & dosagem , Fragmentos de Peptídeos , Ratos , Ratos Wistar , Coloração pela Prata , Comportamento Espacial/efeitos dos fármacosRESUMO
beta-Amyloid plays an important role in the neurodegeneration process of Alzheimer's disease (AD), but its neurotoxic mechanisms are not clear. It has been associated with the increase of oxidative stress and cognitive impairment because the beta-amyloid peptide 25-35 (Abeta((25-35))) has the critical neurotoxic properties of the full-length Abeta(1-42). Our present study shows the role of Abeta((25-35)) when injected into the temporal cortex on the nitric oxide pathways, 3-nitrotyrosine, neuronal death, and the spatial memory of rats 1 month after the injection. Our data showed that Abeta((25-35)) increases oxidative stress, causes neuronal damage, and decreases spatial memory in rats. Notably, the injection of the fraction Abeta((25-35)) caused an increase of nNOS and iNOS immunoreactivity in the temporal cortex and hippocampus. We demonstrated a significant increase of reactive astrocytosis, which was accompanied by neuronal damage in the temporal cortex and hippocampus of rats injected with Abeta((25-35)). These data suggest that the fraction Abeta((25-35)) injected into the temporal cortex might contribute to understanding the role of nitric oxide on the biological changes related to the neuropathological progression and the memory impairment in AD.
Assuntos
Peptídeos beta-Amiloides , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , Óxido Nítrico/metabolismo , Fragmentos de Peptídeos , Lobo Temporal/enzimologia , Animais , Comportamento Animal/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Wistar , Coloração pela Prata/métodos , Percepção Espacial/efeitos dos fármacos , Lobo Temporal/efeitos dos fármacosRESUMO
Docking experiments using a number of published crystal structures of HMG-CoA reductase with the potent hypocholesterolemic agent alpha-asarone are described. The results indicate that alpha-asarone binds in the enzyme's active site. The methoxy groups play a key role in the binding and probably also in its biological activity, as shown by extensive SAR studies reported for analogues of alpha-asarone. The docking results will be valuable for the structure-based design of novel hypolipidemic agents.
Assuntos
Anisóis/química , Simulação por Computador , Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Derivados de Alilbenzenos , Sítios de Ligação , Domínio Catalítico , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
Female and male CFI mice weighing 25-30 g were given 0, 50, 100 or 200 mg/kg of gamma-ethyl-gamma-phenyl-butyrolactone (EPBL) for 5 days intraperitoneally. In the male-dominant lethal phase, males treated with EPBL were mated with untreated females following a 7-day mating schedule with three consecutive mating events. In the female-dominant lethal phase, females treated with EPBL were caged with untreated males. The above dosages and schedule treatments were used. The incidence of pregnancy of females mated on days 1-7 and 8-14 after males were given 200 mg/kg of EPBL and of females given 200 mg/kg when mated to untreated males was decreased. Upon examining surgically exposed uteri and ovaries of pregnant females during the first phase, on gestation days 13-15, an increased incidence of pre-implantation losses with 200 mg/kg of EPBL and an increased incidence of post-implantation losses with 100 and 200 mg/kg was observed. In addition, an increased frequency of pre- and post-implantation losses was seen in females treated with 200 mg/kg. These results support the conclusion that EPBL is a germ cell mutagen and its effects are more pronounced during the post-meiotic stage.
Assuntos
4-Butirolactona/análogos & derivados , 4-Butirolactona/toxicidade , Células Germinativas/efeitos dos fármacos , Mutagênicos/toxicidade , Animais , Corpo Lúteo/anatomia & histologia , Corpo Lúteo/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Perda do Embrião/induzido quimicamente , Epididimo/anatomia & histologia , Epididimo/efeitos dos fármacos , Feminino , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Distribuição Aleatória , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/anatomia & histologia , Testículo/efeitos dos fármacosRESUMO
The aim of this investigation was to determine if extracts of Spirulina maxima reduce the genotoxic damage induced by maleic hydrazide (MH) using the Tradescantia biosssay. Two types of extracts from the alga were prepared: an aqueous extract with two different concentrations, 100 and 500 mg/ml, and a second one, the extract of a 1% solution of dimethyl sulfoxide (DMSO) which corresponded to 100 mg/ml of the alga. The capacity of MH to induce micronuclei (MN) was initially established by administering 0.005, 0.01, and 0.015 mg/ml of the chemical to the Tradescantia inflorescences, and observing its effect after 24 h.The results of this experiment showed a significant MN increase with the two high concentrations tested, although no dose-response effect was observed. For the anticlastogenic assay, the extracts of Spirulina were applied to the inflorescences alone or immediately before the application of MH (0.01 mg/ml) and the induced MN were observed 24 h later. We found that none of the extracts increased the MN level with respect to the untreated plants; also, that MH more or less doubled the basal micronuclei frequency, and finally, that all tested extracts reduced the genotoxic damage caused by MH. The inhibitory indices obtained for the aqueous extracts (100 and 500 mg/ml) and for the DMSO extract were respectively 59, 85, and 56.3%. These data indicate that Spirulina is an anticlastogenic agent and suggest that it is advisable to extend studies on this matter using other biological models.
Assuntos
Antimutagênicos/farmacologia , Cianobactérias/química , Herbicidas/farmacologia , Hidrazida Maleica/farmacologia , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Tradescantia/ultraestruturaRESUMO
Spirulina (Arthrospira), a filamentous, unicellular alga, is a cyanobacterium grown in certain countries as food for human and animal consumption. It is also used to derive additives in pharmaceuticals and foods. This alga is a rich source of proteins, vitamins, amino acids, minerals, and other nutrients. Its main use, therefore, is as a food supplement. Over the last few years, however, it has been found to have many additional pharmacological properties. Thus, it has been experimentally proven, in vivo and in vitro that it is effective to treat certain allergies, anemia, cancer, hepatotoxicity, viral and cardiovascular diseases, hyperglycemia, hyperlipidemia, immunodeficiency, and inflammatory processes, among others. Several of these activities are attributed to Spirulina itself or to some of its components including fatty acids omega-3 or omega-6, beta-carotene, alpha-tocopherol, phycocyanin, phenol compounds, and a recently isolated complex, Ca-Spirulan (Ca-SP). This paper aims to update and critically review the results published over the last few years with regards to these properties. The conclusion is that even if this cyanobacterium has been one of the most extensively studied from the chemical, pharmacological and toxicological points of view, it is still necessary to expand the research in order to have more consistent data for its possible use in human beings.
Assuntos
Proteínas de Bactérias/farmacologia , Suplementos Nutricionais , Animais , Proteínas de Bactérias/uso terapêutico , Humanos , SpirulinaRESUMO
Spirulina has been used in a variety of practical applications in biotechnology and medical sciences. This paper presents the antiviral activity found in a hot water extract (HWE) of a commercial preparation of Spirulina maxima, studied by a microplate inhibition assay, using several viruses. The HWE inhibited the infection for: herpes simplex virus type 2 (HSV-2), pseudorabies virus (PRV), human cytomegalovirus (HCMV), and HSV-1, and the 50% effective inhibition doses (ED(50)) were 0.069, 0.103, 0.142, and 0.333 mg/ml for each virus, respectively. For adenovirus the inhibition was less than 20%, and no inhibition was found for measles virus, subacute sclerosing panencephalitis virus (SSPE), vesicular stomatitis virus (VSV), poliovirus 1 and rotavirus SA-11, at concentrations of 2 mg/ml of the HWE. The highest antiviral activity was for HSV-2, with a selectivity index of 128. The antiviral activity was not due to a virucidal effect. Herpesvirus infection was inhibited at the initial events (adsorption and penetration) of the viral cycle. To initiate the isolation and identification of the compound that exhibits the antiviral activity of S. maxima, some extracts made by using several solvents with different polarity were evaluated by microplate inhibition assay using HSV-2. The highest antiviral activity was detected in the methanol-water 3:1, which suggests that the antiviral activity is probably due to highly polar compounds.
Assuntos
Antivirais/farmacologia , Cianobactérias/química , Herpesvirus Humano 2/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Chlorocebus aethiops , Efeito Citopatogênico Viral/efeitos dos fármacos , Herpesvirus Humano 2/fisiologia , Humanos , Células Vero , Ensaio de Placa ViralRESUMO
Spirulina (Arthrospira), a filamentous, unicellular alga, is a cyanobacterium grown in certain countries as food for human and animal consumption. It is also used to derive additives in pharmaceuticals and foods. This alga is a rich source of proteins, vitamins, amino acids, minerals, and other nutrients. Its main use, therefore, is as a food supplement. Over the last few years, however, it has been found to have many additional pharmacological properties. Thus, it has been experimentally proven, in vivo and in vitro that it is effective to treat certain allergies, anemia, cancer, hepatotoxicity, viral and cardiovascular diseases, hyperglycemia, hyperlipidemia, immunodeficiency, and inflammatory processes, among others. Several of these activities are attributed to Spirulina itself or to some of its components including fatty acids omega-3 or omega-6, beta-carotene, alpha-tocopherol, phycocyanin, phenol compounds, and a recently isolated complex, Ca-Spirulan (Ca-SP). This paper aims to update and critically review the results published over the last few years with regards to these properties. The conclusion is that even if this cyanobacterium has been one of the most extensively studied from the chemical, pharmacological and toxicological points of view, it is still necessary to expand the research in order to have more consistent data for its possible use in human beings.
Assuntos
Animais , Humanos , Suplementos Nutricionais , Proteínas de Bactérias/farmacologia , Proteínas de Bactérias/uso terapêuticoRESUMO
The reproductive toxicity of gamma-ethyl-gamma-phenyl-butyrolactone (EPBL, CAS 53380-21-5), a new anticonvulsant and hypnotic drug, was investigated by performing fertility and peri- and post-natal studies in mice. In both studies, EPBL was administered by gavage at 0, 50, 10, or 200 mg/kg doses. The first study found parent toxicity as measured by reduced body weight at the higher dose. At the same dose, the number of live fetuses was decreased. However, neither male or female fertility nor the reproductive performance of mice were affected. The results of the second study showed that the only negative effects were a depression of maternal weight gain and a decrease in body weight of the litter at birth which was 200 mg/kg. A reduction in the survival rate was also seen. There was no evidence that treatment of F0 females from day 15 of pregnancy to day 21 post-partum affected either the reproductive capacity of the F1 offspring or the development of F2 progenies. The non observed effects levels (NOEL) for both studies can be estimated at 100 mg/kg.
Assuntos
Anticonvulsivantes/toxicidade , Fertilidade/efeitos dos fármacos , Hipnóticos e Sedativos/toxicidade , Teratogênicos/toxicidade , 4-Butirolactona/análogos & derivados , 4-Butirolactona/toxicidade , Animais , Peso ao Nascer/efeitos dos fármacos , Feminino , Masculino , Camundongos , Nível de Efeito Adverso não Observado , Gravidez , Aumento de Peso/efeitos dos fármacosRESUMO
La Spirulina, alga azul-verde filamentosa unicelular, ha sido consumida desde tiempos remotos en México y Africa Central, en donde crece de manera seminatural o natural. Actualmente se cultiva en algunos países por metódos sintéticos. Hasta recientemente el interés en esta alga se centraba en su valor nutritivo que mostró ser casi igual al de proteínas de otras plantas. Sin embargo, algunos estudios preclínicos sugieren que también poseen propiedades terapéuticas interesantes, tales como hipocolesterolemiante, inmunológica, antiviral y antimutagénica. Esto ha llevado a evaluaciones toxicológicas detalladas. El contenido de ácidos nucleicos y la presencia de metales, de aminas biogéncias y de compuestos químicos orgánicos, han sido negativos o están bajo de las concentraciones tolerables recomendadas por agencias internacionales de regulación de alimentos. Los experimentos en animales de toxicidad aguda, subcrónica, crónica, de reproducción, mutagenicidad y teratogenicidad, no han revelado ningún efecto adverso al alga, en todos los casos, la cantidad de Spirolina administradas a los animales fueron iguales o superiores al consumo humano. Sin embargo, hay pocos estudios de los efectos de consumo de Spirulina en humanos. Esta área necesita más estudios
Assuntos
Humanos , Ácidos Nucleicos/toxicidade , Aminoácidos/uso terapêutico , Carotenoides/uso terapêutico , Cianobactérias , Herpes Simples/dietoterapia , Herpes Simples/prevenção & controle , Hipercolesterolemia/dietoterapia , Hipercolesterolemia/prevenção & controle , Neoplasias/prevenção & controle , Proteínas de Bactérias/uso terapêutico , Vitamina B 12/uso terapêuticoRESUMO
Se estudiaron los efectos del indorrenato, un nuevo fármaco antihipertensivo, sobre la fertilidad, desarrollo peri-postnatal y embrionario en rata, a dosis de 0, 10, 20, 40 y 60 mg/kg/día, administrados oralmente. Durante el estudio de fertilidad, con excepción de la dosis de 60 mg/kg, ningún tratamiento afectó el peso de los progenitores, la fertilidad, el peso fetal o la sobrevivencia. Tampoco las dosis bajas dieron lugar a retardo en aparición del reflejo de enderezamiento, despliegue de pabellón auricular y respuesta al ruido. Las dosis de 40 y 60 mg/kg, por su parte, disminuyeron significativamente el número de fetos vivos y aumentó el de reabsorciones embrionarias. En el estudio peri-postnatal, 40 y 60 mg/kg aumentaron el número de fetos muertos al nacer, y la segunda, afectó también su sobrevivencia, el aumento ponderal y el reflejo de caída. La capacidad reproductiva de la generación F1 no fue modificada. El fármaco no provocó embriotoxicidad ni teratogenicidad, administrado durante el período de organogénesis, en contraste con la serotonina, de la cual es análogo estructural. Se concluye que el indorrenato hasta la dosis de 20 mg/kg, que representa aproximadamente 1200 veces la que se pretende utilizar en pacientes hipertensos, no ejerce efecto toxico aparente sobre la reproducción, desarrollo embrionario y fetal en rata
Assuntos
Ratos , Animais , Anti-Hipertensivos/toxicidade , Relação Dose-Resposta a Droga , Estruturas Embrionárias , Fertilidade/efeitos dos fármacos , Desenvolvimento Fetal/efeitos dos fármacos , Ratos WistarRESUMO
The toxicity profiles of the phenyl alcohol amides: 4-hydroxy, 4-ethyl, 4-phenylbutyramide (HEPB) and two lower homologous: 3-hydroxy, 3-ethyl, 3-phenylpropionamide (HEPP) and 2 hydroxy, 2-ethyl, 2-phenylacetamide (HEPA) were studied in mice. TD50 value was determined by oral administration and LD50 by oral and intraperitoneal routes. The results indicate that HEPP is less toxic than the others, both of which had very similar toxicity. Furthermore, the teratogenic potential of HEPB was investigated in mice after oral administration. The compound was administered on days 6 - 15 of gestation at doses of 0, 5, 25, 50 or 100 mg/kg of weight. On day 17 of pregnancy the mice were sacrifed and the pups examined. An increase of body weight in both mothers and fetuses was observed at 25 and 50 mg/kg, as a sign of maternal toxicity. Considering the litter data, embryotoxicity and fetotoxicity were only shown at the highest dose. Howeever, the HEPB treatment did not result in malformations of live fetuses or resorptions when the implantations were considered as the individual entity
Assuntos
Camundongos , Animais , Amidas/farmacologia , Anticonvulsivantes/toxicidade , Teratogênicos/toxicidadeRESUMO
La planta Guatteria gaumeri Greenman (Annonaceae) se utiliza en medicina tradicional para el tratamiento de la hipercolesterolemia y la colelitiasis. El principio activo mayoritario es la alfaasarona que ha sido aislado y posteriormente sintetizado, además de 16 análogos derivados de 4-propenil-1,2-dimetoxibencenos 5-sustituidos. Dosis de 80 mg/kg de alfa-asarona y de los derivados amino (NH2-) y metoxi (MeO-), administradas oralmente por siete días a ratas hipercolesterolémicas, produjeron decrementos del 57.3, 37.5 y 46.9 por ciento del colesterol y del 42.5, 67.6 y 17.2 por ciento de los triglicéridos, respectivamente; al alfa-asarona redujo además 80.6 por ciento del peso de los cálculos biliares en hamsters. Algunos de los otros análogos también presentaron actividad hipolopidémica importante. Estudios en hepatocitos sugiere que parte del efecto lipidémico es debido a disminución en la secreción de los lípidos. La alfa-asarona no produjo toxicidad en ratas dada por vía oral durante 28 días, con dosis de 10 ó 50 mg/kg y tampoco genotoxicidad mediante la prueba de dominantes letales. Sin embargo, la exposición in vitro de hepatocitos a concentraciones micromolares indujo alteraciones morfológicas, acumulación de triacilglicerol e inhibición de la síntesis y secreción de proteínas. A su vez, las pruebas de Ames y de frecuencia de intercambio de cromátides hermanas en linfocitos humanos, sí revelaron genotoxicidad. No se produjo teratogenia en ratas administrada durante la organogénesis, pero en ratones se encontró hidrocefalia, defectos en esqueleto, y baja de peso corporal. El efecto tóxico de la alfa-asarona plantea precausión en el uso de la planta en tanto no se efectúen investigaciones en otras especies animales; es importante también analizar la toxicología de los compuestos análogos
Assuntos
Humanos , Animais , Ratos , Guatteria gaumeri/farmacologia , Guatteria gaumeri/toxicidade , Hipercolesterolemia/terapia , Medicina TradicionalRESUMO
Se investigó el potencial embriotóxico y fetotóxico de Spirulina en ratón. El alga fue administrada a animales gestantes a concentraciones de 0, 10, 20 y 30 g/100 en la dieta, durante los días 7-13, 1-13 y 1-19 de la gestación. El día 19 se sacrificaron las madres y se examinaron los cuernos uterinos para contar los fetos vivos, muertos y reabsorbidos. Los fetos vivos se pesaron, analizándose las malformaciones externas, esqueléticas y viscerales. No se encontró diferencia significativa entre los lotes en cuanto al número de reabsorciones o de fetos afectados, ya fuese considerando la camada como unidad de análisis, o tomando en cuenta el número total de fetos afectados. Estos resultados indican que la alimentación de ratones gestantes hasta con una concentración de 30 g/100 del alga, no provoca efectos embriotóxicos ni teratogénicos. La cantidad de alimento ingerida por los animales a esa concentración, es exageradamente superior al posible consumo humano
Assuntos
Gravidez , Camundongos , Animais , Feminino , Anormalidades Induzidas por Medicamentos , Feto/efeitos dos fármacos , Proteínas/toxicidade , Reprodução/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colo do Útero/efeitos dos fármacosRESUMO
El alga Spirulina es considerada como un complemento proteínico par auso humano y animal. Todas las proteínas unicelulares destinadas a este propósito deben someterse previamente a investigaciones toxicológicas detalladas, en animales de laboratorio u otros modelos experimentales. Como parte de esas investigaciones, el objetivo del presente estudio fue el de evaluar su potencial teratogénico en ratas. El alga fue administrada en la dieta a concentraciones de 0,10,20 y 30 g/100g durante los días 7-14,1-14, y 1-21 de la gestación. Las hembras fueron sacrificadas antes de término, y los fetos examinados con el fin de detectar anormalidades externas, viscerales y esqueléticas. Según se determinó, los pesos maternal y fetal no se vieron afectados, y tampoco se produjo feto-toxicidad o teratogenicidad. Se considera importante llevar a cabo estos mismos estudios en otras especies animales