Comparative study with dry crude extracts of Ananas comosus L. Merril using LC50 and erythrocyte osmotic fragility as toxicity parameters / Estudio comparativo con extractos crudos secos de Ananas comosus L. Merril utilizando CL50 y fragilidad osmótica eritrocitaria como parámetros de toxicidad

Ananas comosus, conocido popularmente como piña, tiene una anatomía de planta bien definida y numerosos fitoquí­micos farmacológicamente activos. Algunos de éstos son responsables del potencial antimicrobiano de la especie, que ha sido ampliamente estudiado dada la resistencia bacteriana a los antibióticos actualmente utilizados. Teniendo esto en cuenta, se define que la característica principal de un medicamento es la ausencia de efectos tóxicos, por lo tanto, es necesario buscar datos sobre la toxicidad de A. comosus, colaborando para su posible uso como fármaco. Comparando extractos hidroalcohólicos de las hojas de la corona, cáscara y pulpa de la infrutescencia, fue posible determinar que los tres extractos probados no son tóxicos, siendo el de menor toxicidad para Artemia salina Leach (extracto de hojas con CL50 igual a 994 μg/mL) y a sangre de cordero (extracto de pulpa con porcentaje de hemólisis igual a 0,83%). Los estudios sobre principios y metodologías similares a los utilizados aquí han encontrado resultados comparables que indican la baja toxicidad de la planta. Estos resultados aportan a las investigaciónes que promueven el uso de la piña como agente fitoterapéutico y reafirman su presencia en el Sistema Único de Salud de Brasil.

Ananas comosus, popularly known as pineapple, has well defined plant anatomy and numerous pharmacologically active phytochemicals. Some of these are responsible for the species antimicrobial potential, which has been widely studied given the bac­terial resistance to the currently used antibiotics. Considering this, it is defined that the main characteristic of a drug is the absence of toxic effects, thus, there is a need to seek data regarding the toxicity of A. comosus, collaborating for its possible use as a drug. Comparing hydroalcoholic extracts from the crown leaves, skin and pulp of the infructescence, it was possible to determine that the three tested extracts are non-toxic, being the one with the lowest toxicity to Artemia salina Leach (leaves extract with LC50 equal to 994 μg/mL) and to lamb's blood (pulp extract with percentage of haemolysis equal to 0.83%). Studies concerning principles and methodologies similar to those used here have found comparable results stating the low toxicity of the plant. These results contribute to the research that promotes the use of pineapple as a phytotherapeutic agent and reaffirms its presence in the Brazilian Unified Health System.

Evaluación toxicológica y de metales (Cu, Pb, Ni, Zn y Cd) en el sedimento del reservorio Paiva Castro en Mairiporã-SP, Brasil / Toxicological and metal evaluation (Cu, Pb, Ni, Zn and Cd) in the sediment of Paiva Castro reservoir, in Mairiporã-SP, Brasil

El hombre ha cambiado el ambiente para sostener la demanda global de recursos naturales como el agua. La gestión de los cuerpos hídricos tiene que ser constante, con el propósito preventivo y correctivo, dependiendo del estado de antropización de cada sistema. El objetivo de este artículo fue analizar la toxicidad del sedimento y los metales Mn, Zn, Pb, Ni, Cd y Cu, en el reservorio Paiva Castro, que abastece la Region Metropolitana de São Paulo. Se realizaron 2 muestreos (Mayo 2011, estación seca y Enero de 2012, estación húmeda) y se analizaron 5 puntos próximos a la captación de agua por la Companhia de Saneamento Básico do Estado de São Paulo. Se realizaron ensayos de toxicidad aguda y crónica en sedimento, a través de ensayos biológicos con el cladócero Daphnia similis y el insecto Chironomus xanthus. El tratamiento de datos se realizó con el test de Fisher (mortalidad). El nivel de asociación entre las variables en sedimento y en los test ecotoxicológicos fueron evaluados por test no-paramétricos, a través del coeficiente de correlación de Spearman's. Los resultados del presente trabajo señalaron bajas concentracones de metales en el sedimento del área de estudio y ausencia de toxicidad en los organismos ensayados. Se puede concluir que área estudiada del reservorio Paiva Castro se encuentra poco impactada por los metales, sin efectos directos sobre la calidad de vida los organismos bentónicos: D. similis y C. xanthus.

Man had changed the natural environment in an attempt trying to supply the global demand for resources. The management of the hydric bodies has to be constant, with preventive and corrective purpose, depending on the eutrophization state of each one. The objective of this article was to analyze the sediment toxicity and the metals Mn, Zn, Pb, Ni, Cd and Cu, in the Paiva Castro reservoir, that supply the Metropolitan Region of São Paulo. It was made 2 collections (May 2011, dry season and January 2012, wet season). It was analyzed 5 points next to the water captation station by the Companhia de Saneamento Básico do Estado de São Paulo. The sediment was analyzed as for acute and chronic toxicity through bioassays with the cladocerans Daphnia similis and the insect Chironomus xanthus. Data treatment was done with Fisher Exact Test (mortality). The association level between the variables in sediment and ecotoxicological tests was available in non-parametric tests, through the Spearman's correlation coefficient. Oriented on the results presented in this work, pointing low concentrations of heavy metals in the sediments presented in the collect local, and the absence of toxicity, we can say that at this reservoir, at least in the collect area, it's low impacted, not implicating in direct interferences in the quality of life of benthonic organisms.

Acute toxicity study of a polysaccharide based hydrogel from linseed for potential use in drug delivery system

ABSTRACT Linseed hydrogel (LSH) was evaluated by acute toxicity for its potential application in oral drug delivery design. White albino mice and rabbits were divided in four groups (I-IV) and different doses of LSH (1, 2 and 5 g/kg body weight) were given except to the control group (I) that was left untreated. Rabbits were monitored for eye irritation, acute dermal toxicity and primary dermal irritation, whereas, body weight, food and water consumption, hematology and clinical biochemistry, gross necropsy and histopathology of vital organs were scrutinized in mice. LSH was considered safe after eye irritation test as no adverse signs or symptoms were seen in the eye. In dermal toxicity and irritation study, skin of treated rabbits was found normal in color without any edema or erythema. After oral administration, there was no sign of any abnormalities in treated group animals (II-IV). The hematology and clinical biochemistry of treated group animals was comparable with the control group. Histopathology of vital organs has not shown any lesion or abnormalities. In the light of these outcomes, it can be concluded that LSH is not a hazardous biomaterial and could be incorporated as an excipient in oral and dermal preparations.

Ecotoxicidad de nanopartículas metálicas y superparamagnéticas de óxido de hierro en dos especies / Ecotoxicity of metalic and superparamagnetics iron oxide nanoparticles in two species

Introducción: la nanotecnología y el empleo de materiales a nano escala son un área relativamente nueva de la ciencia y la tecnología con un gran crecimiento en el mercado global. Muchos de los productos no cuentan con estudios que garanticen su uso seguro, tanto para el hombre como para los ecosistemas. Los estudios ecotoxicológicos permiten evaluar los efectos de un determinado xenobiótico sobre especies representativas de los diferentes compartimentos ambientales. Objetivo: evaluar los efectos tóxicos de nanopartículas de Ag, Au, Ag/Ag y superparamagnéticas de óxido de hierro, en dos especies bioindicadoras de los ecosistemas terrestre y acuático. Métodos: como parte de los estudios de seguridad se realizaron ensayos de toxicidad aguda por contacto en lombriz de tierra de la especie Eisenia andrei, con una duración de 96 horas y estudios en anfibios de la especie Osteopillus septentrionales en diferentes etapas del desarrollo (embrionario y larval). Se evaluó la ocurrencia de mortalidad y de efectos tóxicos, en el caso del ensayo en lombriz de tierra; se determinó además la viabilidad celular. Resultados: los efectos tóxicos más significativos en el caso de la lombriz de tierra fueron, la ocurrencia de alteraciones fisiológicas y conductuales al ser expuesta a NPs de Ag de 3 nm y superparamagnéticas de óxido de hierro, estas últimas provocaron citotoxicidad a la concentración 1,38 mg/mL. En el caso de los anfibios se evidenció toxicidad en NPs de Ag 3 nm y superparamagnéticas de óxido de hierro. Conclusiones: todas las nanopartículas mostraron efectos tóxicos en las especies bioindicadoras evaluadas(AU)

Introduction: Nanotechnology and the use of nanoscale materials are a relatively new area of science and technology with big growth in the global market. Many of these products don't have studies that guarantee their safe use, both for man and for ecosystems. Ecotoxicological studies allow the evaluation of the effects of a particular xenobiotic on representative species of the different environmental compartments. Objective: To evaluate the toxic effects of nanoparticles of Ag, Au, Ag / Ag and super paramagnetic iron oxide in two bioindicators of terrestrial and aquatic ecosystems. Methods: Acute contact toxicity tests were carried out on ground worm of the Eisenia andrei species, with a duration of 96 hours and studies on amphibians of the species Osteopillus septentrionales at different stages of development (embryonic and larval). The occurrence of mortality and toxic effects was evaluated in the case of earthworm test; cell viability was also determined. Results: The most significant toxic effects in the case of earthworms were the occurrence of physiological and behavioral alterations when exposed to 3 nm Ag of superparamagnetic iron oxide nanoparticles, where the latter caused cytotoxicity at concentration of 1.38 mg / mL. In the case of amphibians, toxicity was evidenced in Ag 3 nm nanoparticles and superparamagnetic iron oxide. Conclusions: All nanoparticles showed toxic effects in the evaluated bioindicator species(AU)

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These findings also justify the traditional use of the plant for treating pain.

Acute silver toxicity to Cnesterodon decemmaculatus (Pisces: Poeciliidae) in a river with extreme water-quality characteristics / Toxicidad aguda de la plata sobre Cnesterodon decemmaculatus (Pisces: Poeciliidae) en un río con características extremas de calidad de agua

Abstract. A 96 h acute silver toxicity test was performed in order to determine silver toxicity (LC50) to a local fish species (Cnesterodon decemmaculatus) in a river with extreme water-quality characteristics (Pilcomayo River, South America) and evaluate a cross-fish-species extrapolation of the Biotic Ligand Model. The dissolved silver concentrations tested were 0.095, 0.148, 0.175 and 0.285 mg Ag L−1. The 96 h Ag LC50 calculated for C. decemmaculatus was 0.14 mg L−1 (0.18 - 0.10) and the value predicted by BLM for Pimephales promelas was 0.051 mg Ag L−1. Test water elevated hardness may have exerted some protective effect. High mean water pH may have exerted a major protective effect by reducing silver free ion form and causing silver precipitation. The mortality pattern observed in this toxicity test may lend some support to a relationship between gill silver accumulation and mortality. A cross-fish-species extrapolation of Ag BLM for P. promelas was not valid in Pilcomayo River water and experimental conditions of this toxicity test.

Con el objeto de determinar la toxicidad de la plata en un pez nativo (Cnesterodon decemmaculatus), se llevó a cabo un ensayo estático de toxicidad aguda a 96 horas en un agua natural con características de calidad de agua, extremas (río Pilcomayo, Sudamérica). Asimismo, se evaluó una posible extrapolación inter-especie del Modelo del Ligando Biótico en el agua experimental. La concentración inicial de plata en solución en los distintos tratamientos fue de 0,095; 0,148; 0,175 y 0,285 mg Ag L −1 . La CL50 a las 96 horas calculada para C. decemmaculatus fue de 0,14 (0.18 - 0.10) mg Ag L−1 y el valor predicho por el BLM para Pimephales promelas fue de 0,051 mg Ag L−1. La elevada dureza del agua experimental pudo haber tenido algún efecto protector frente a la toxicidad de la plata. El valor medio de pH del ensayo fue elevado y posiblemente tuvo un gran efecto protector por reducción de la forma iónica libre y precipitación del metal. El patrón de mortalidad observado en este ensayo de toxicidad apoyaría la relación causa-efecto entre acumulación de plata en las branquias y mortalidad. La extrapolación inter-especie del BLM para P. promelas no resultó válida en el agua del río Pilcomayo y en las condiciones experimentales de este ensayo.

Toxicidad en peces de herbicidas formulados con glifosato / Toxicity in fishes of herbicides formulated with glyphosate

En nuestro país existe una gran extensión de hectáreas cultivadas con soja transgénica, la misma ha sido modificada genéticamente para soportar la acción de un herbicida denominado glifosato. Debido a la gran cantidad de formulaciones comerciales que incluyen glifosato es de importancia analizar el impacto ambiental producido por éstas. La evaluacion de la toxicidad aguda de dos herbicidas comerciales formulados con glifosato y de una solución del mismo; frente a peces de la especie Poecilia reticulata "lebistes" acusa que una de las soluciones produce mortalidad del 100 % de los especimenes a 100 μl/l (equivalente a 48 mg/l de principio activo); la otra a 50 μl/l (equivalente a 24 mg/l de principio activo) y la solución formulada con glifosato puro no produce mortalidad aún a concentraciones de 400 mg/l. Utilizando dosis sub letales en función de los datos obtenidos en el ensayo de toxicidad aguda se determinó que a largo plazo especimenes de Cyprinus carpio haematopterus "carpa koi", manifestaron severas alteraciones hematológicas principalmente frente a una de las formulaciones evaluadas.

Nowadays, transgenic soya, modified in order to withstand the impact of the herbicide glyphosate, in one of the main crops grown in Argentina. Due to the large number of commercial formulations that include this drug, is important to analyze both, the acute and chronic environmental impact that they cause. Here the acute toxicity of two commercial herbicides glyphosatebased toward the fish Poecilia reticulate "guppy" was evaluated and compared with pure glyphosate solutions. Interestingly, while commercial herbicides formulations induce a 100% of mortality at concentration ranged between 50 and 100 μl/l, the pure glyphosathe does not present mortality even at doses higher than 400 mg/l. When some long term effects toward Cyprinus carpio haematopterus "koi" were determined by using the sub-lethal doses already calculated it was demonstrated that one of the commercial herbicides induces severe haematological alterations.

Toxicidad aguda oral de Solanum torvum Sw (prendejera) / Acute oral toxicity of Solanum torvum Sw (prendejera)

Introducción: Solanum torvum Sw, conocida popularmente como prendejera, es una planta medicinal empleada por la población como antimicrobiano, antiartrítico, entre otras propiedades. Esta planta no reporta estudios de toxicidad de tipo agudo, solo aparecen reportados estudios de toxicidad a largo plazo. Objetivos: evaluar la toxicidad aguda oral por el método de las clases de la decocción de hojas y tallos Solanum torvum por vía oral en ratas Sprague Dawley. Métodos: se realizó un ensayo de toxicidad aguda oral por el método de las clases. La administración se hizo por vía oral a una dosis única de 2 000 mg/kg de peso corporal de una decocción de la planta S torvum. Se efectuaron los estudios correspondientes de anatomía patológica, que evidenciaran toxicidad de la sustancia ensayada. Resultados: la sustancia evaluada no produjo signos clínicos que demostraran toxicidad, ni muerte animal, no se reportaron alteraciones en el peso corporal de los biomodelos; macroscópicamente no se comprobaron alteraciones de valor diagnóstico. Conclusiones: la sustancia ensayada por vía oral, a dosis única, se enmarca como sin clasificar, en el modelo animal y nivel de dosis utilizado bajo las condiciones experimentales observadas

Introduction: Solanum torvum Sw, traditionally known as prendejera, is a medicinal plant used by the population as antimicrobial and anti-inflammatory agent among other properties. No acute toxicity studies are reported on this plant, just long-term toxicity studies. Objectives: to evaluate the acute oral toxicity by the class method using decoction of Solanum torvum leaves and stems orally administered to Sprague Dawley rats. Methods: an acute oral toxicity test based on the class method was conducted. The S torvum plant decoction was administered in one dose of 2000 mg/kg of body weight. Pathological anatomy studies were performed to analyze the toxicity in the tested substance. Results: the evaluated substance did not show any clinical signs of toxicity or animal deaths; no alterations in the body weight of the experimental models were found. There were no alterations of diagnostic value according to the macroscopic analysis. Conclusions: the tested decoction, orally administered at one dose, is regarded as unclassified for the animal model and the dosage used under the observed experimental conditions

Study of acute toxicity and investigation of the presence of β-N-methylamino-L-alanine in the Gunnera manicata L. a species native to Southern Brazil / Estudo da toxicidade aguda e investigação da presença de β -N-metilamino-L-alanina no manicata Gunnera L. uma espécie nativa sul do Brasil

Gunnera (Gunneraceae) forms a complex association with the cyanobacterium Nostoc puctiforme L. Gunnera-Nostoc symbiosis is the only one reported involving a flowering plant, and results in the formation of the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA). The species Gunnera manicata L., for which phytochemical, pharmacological and toxicological studies are lacking, is found in Southern Brazil. Therefore, acute toxicity and the presence of neurotoxic amino acid were investigated in aqueous extracts of G. manicata. The acute toxicity test was conducted by administering aqueous root extract of G. manicata at a concentration of 2000 mg/kg in a single dose orally to Wistar rats. Lethality was monitored daily for 14 days after treatment. The relative mass of organs was analyzed by one-way ANOVA and macroscopic changes were investigated. The analysis of BMAA, a procedure performed by GC/MS, involved a preliminary derivatization step. The ESI-MS/MS analysis was done by direct infusion. The present study demonstrated absence of neurotoxin in the samples of G. manicata analyzed and absence of acute toxicity in aqueous root extracts. These data confirm that extracts from the roots of G. manicata have a high margin of drug safety.

Gunnera (Gunneraceae) forma uma complexa associação com a cianobactéria Nostoc puctiforme L. A simbiose Gunnera-Nostoc é a única relatada envolvendo uma angiosperma e, em decorrência desta, ocorre a formação da neurotoxina β-N-metilamino-L-alanina (BMAA). No sul do Brasil, encontra-se a espécie G. manicata L., da qual não constam, na literatura científica, estudos fitoquímicos, farmacológicos e toxicológicos. Assim, o presente estudo avaliou a toxicidade aguda e a presença da neurotoxina BMAA em extratos aquosos de G. manicata. O ensaio de toxicidade aguda foi realizado com extrato aquoso das raízes de G. manicata na concentração de 2000 mg/kg, administrado em dose única via oral em ratos Wistar. Letalidade foi observada diariamente durante 14 dias pós-tratamento. Após a eutanásia, a massa relativa dos órgãos foi analisada por ANOVA de uma via e investigou-se a presença de alterações macroscópicas. A análise do BMAA por CG/EM envolveu uma etapa preliminar de derivatização, já a análise por ESI-EM/EM foi realizada por infusão direta. O presente estudo demonstrou a ausência da neurotoxina nas amostras de G. manicata analisadas bem como a ausência de toxicidade aguda no extrato aquoso das raízes. Esses dados demonstram alta margem de segurança dos extratos testados.

Evaluación del extracto fluido de Pluchea carolinensis (Jacq) G Don. por el método de clases de toxicidad en ratas / Evaluation of fluid extract from Pluchea carolinensis (jacq) G Don by the toxicity class method in rats

Introducción: la salvia de playa, Pluchea carolinensis (Jacq) G Don., ha sido utilizada en la medicina tradicional para eliminar fiebres, digestiones lentas, dolores de riñones, de cabeza, ronqueras. Objetivos: clasificar al extracto fluido de salvia comenzando por el nivel de dosis 2 000 mg/kg, según el método de clase de toxicidad aguda. MÉTODOS: se evaluó el extracto fluido de hojas secas de salvia de playa mediante el ensayo de las clases de toxicidad, que permite clasificar la sustancia en un rango de toxicidad. Se utilizaron 6 hembras de la sublínea Cenp:SPRD, procedentes del CENPALAB. Se les administró una dosis única de 2 000 mg/kg de peso corporal del extracto fluido de salvia de playa por vía oral, previo ayuno. El período de observación fue de 14 d, en el cual se monitorearon las condiciones ambientales diariamente, la aparición de signos de toxicidad y muerte, así como el peso corporal en los días 0, 7 y 14 del ensayo. Resultados: los animales alcanzaron 100 por ciento de supervivencia. No se observaron signos de toxicidad, tras la administración de la sustancia ensayo en la dosis máxima de 2 000 mg/kg. En la evaluación anatomopatológica no se observaron alteraciones macroscópicas en la superficie externa de los animales y en ninguna de sus cavidades, órganos y tejidos. Conclusiones: de acuerdo con el método de toxicidad de clases la sustancia no es clasificada, DL50 es mayor que 2 000 mg/kg.

Introduction: beach salvia, Pluchea carolinensis (Jacq)G Don has been used for long in traditional medicines to abate fevers, slow digestion, kidney pains, headache, and hoarseness. Objectives: to classify fluid extract from beach salvia according to the acute toxicity class method, by starting with a 2000 mg/kg dose. Methods: the fluid extract from beach salvia dry leaves was evaluated through the toxicity class test that allows classifying the substance into a range of toxicity. Six Cenp:SPRD subline female rats from CENPALAB (Center of lab animal production) were used. They were orally administered a single dose of 2000 mg of beach salvia fluid extract per kg of body weight on fasting. The observation period was 14 days to monitor daily environmental conditions, the occurrence of toxicity signs and death as well as the body weight at 0th,7th and 14th day. Results: the six rats survived. No sign of toxicity was observed after the administration of the extract at 2000 mg/kg dose. In the anatomopathological assessment, no macroscopic alterations were seen in the external surface or in the cavities, organs and tissues of the animals. Conclusions: according to this toxicity class method, the substance is not classified since LD50 is higher than 2 000 mg/kg.

Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex.

Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.