ABSTRACT
In the current work, cytotoxicity and genotoxicity of different organoselenium compounds were examined using Trypan blue exclusion and alkaline comet assays with silver staining respectively. Leukocytes were subjected to a 3-hour incubation with organoselenium compounds at concentrations of 1, 5, 10, 25, 50, and 75 µM, or with the control vehicle (DMSO), at a temperature of 37 °C. The viability of the cells was evaluated using the Trypan blue exclusion method, while DNA damage was analyzed through the alkaline comet assay with silver staining. The exposure of leukocytes to different organoselenium compounds including i.e. (Z)-N-(pyridin-2-ylmethylene)-1-(2-((2-(1-((E)-pyridin-2-ylmethyleneamino)ethyl)phenyl)diselanyl)phenyl)ethanamine (C1), 2,2'(1Z,1'E)-(1,1'-(2,2'-diselanediylbis(2,1-phenylene))bis(ethane-1,1-diyl)) bis(azan-1-yl-1-ylidene)bis -methan-1-yl-1-ylidene)diphenol (C2), and dinaphthyl diselenide (NapSe)2, At concentrations ranging from 1 to 5 µM, no significant DNA damage was observed, as indicated by the absence of a noteworthy increase in the Damage Index (DI). Our results suggest that the organoselenium selenium compounds tested were not genotoxic and cytotoxic to human leukocytes in vitro at lower concentration. This study offers further insights into the genotoxicity profile of these organochalcogens in human leukocytes. Their genotoxicity and cytotoxicity effects at higher concentration are probably mediated through reactive oxygen species generation and their ability to catalyze thiol oxidation.
ABSTRACT
Introdução: O uso de plantas como inseticidas podem substituir muitos produtos sintéticos por apresentarem baixa toxicidade para os animais e biodegradação no ambiente. A espécie Lantana montevidensis (Spreng.) Briq. (Verbenaceae), chumbinho, é um vegetal subarbustivo rico de compostos secundários para a sua defesa. O modelo experimental com Drosophila melanogaster tem sido usada para estudos, por apresentar vantagens, pois tem fácil manuseio e rápida taxa de reprodução. Objetivo: Avaliar a composição química e efeito inseticida do óleo essencial (OE) de L. montevidensis contra D. melanogaster. Metodos: O OE das folhas secas provenientes do Crato-CE, Brasil, foi extraído por hidrodestilação e foi analisado por CG/EMS para identificação dos constituintes. No ensaio foi avaliada a mortalidade e geotaxia negativa das moscas, em que elas foram expostas a diferentes concentrações do OE (3-30,5 µg/mL do óleo essencial/ar). Um total de vinte moscas adultas foram submetidas à diapausa por meio de resfriamento e em seguidas foram colocadas em frascos de 300 mL, cuja parte inferior havia papel filtro impregnado com 1 mL de sacarose a 20 por cento em água destilada. Na parte superior (tampa) foi afixado um papel filtro para a aplicação do produto a ser testado, nesse caso o OELM. As leituras foram realizadas a cada 3, 6, 12 e 24 h. Resultados: Os resultados mostraram que o OE apresentou o ß-Cariofileno (34,96 por cento), o Germacreno D (25,49 por cento) e o Biciclogermacreno (9, 78 por cento) como componentes majoritários, no ensaio inseticida houve uma CL50 na concentração de 15,14 µg/mL em 3 h de exposição, e houve um efeito significativo nos danos do aparelho locomotor das moscas.mConclusão: Este estudo fornece evidências que esse OE apresenta-se como um potencial bioinseticida(AU)
Introducción: el uso de plantas como insecticidas puede sustituir muchos productos sintéticos porque tienen baja toxicidad para los animales y son fácilmente biodegradables en el medio ambiente. La especie Lantana montevidensis (Spreng.) Briq. (Verbenaceae), Chumbinho, es una planta sub-arbustiva rica en metabolitos secundarios para su defensa. El modelo experimental en Drosophila melanogaster se ha utilizado para varios tipos de estudios, presenta algunas ventajas como: fácil manejo y tasa de reproducción rápida. Objetivo: evaluar la composición química y el efecto insecticida de aceite esencial (OE) de L. montevidensis contra las D. melanogaster. Métodos: el OE de hojas secas del Crato-CE, Brasil, se extrajo por hidrodestilación y se analizó por GC/EMS para identificar los constituyentes. En el test se evaluó la mortalidad y geotaxia negativas de las moscas, donde fueron expuestos a diferentes concentraciones de OE (3-30,5 µg/mL de aceite esencial/aire). Un total de veinte moscas adultas se sometieron a diapausa por enfriamiento y seguido se colocaron en botellas de 300 mL, la parte inferior contenido papel de filtro impregnado con 1 mL de 20 por ciento de sacarosa en agua destilada. En la parte superior (tapa) se haya colocado un papel de filtro para la aplicación del producto a ensayar, la OELM. Las lecturas se realizaron cada 3, 6, 12 y 24 h. Resultados: Los resultados mostraron que el OE presenta la ß-cariofileno (34,96 por ciento), el germacreno D (25,49 por ciento) y bicyclogermacrene (9,78 por ciento) como componentes principales en el ensayo insecticida había una CL50 de la concentración de 15,14 µg/mL en 3 h de exposición, y había un un efecto significativo en el daño del aparato locomotor de las moscas. Conclusión: este estudio proporciona evidencia de que este OE o se presenta como un biopesticida potencial(AU
Introduction: The use of plants as insecticides may be an alternative to many synthetic products because their toxicity to animals is low and they are easily biodegradable in the environment. The species Lantana montevidensis (Spreng.) Briq. (Verbenaceae), chumbinho, is a subshrub rich in secondary metabolites it uses for its own defence. The experimental model for Drosophila melanogaster has been used in several types of studies. Some of its advantages are its easy management and its fast rate of reproduction. Objective: Evaluate the chemical composition and insecticidal effect of the essential oil (EO) of L. montevidensis against D. melanogaster. Method: EO of dry leaves from Crato-CE, Brazil, was extracted by hydrodistillation and analyzed by GC/EMS to identify its constituents. As part of the test, evaluation was conducted or the mortality and negative geotaxis of the flies, to attain which they were exposed to different concentrations of the EO (3-30.5 µg/mL essential oil/air). A total 20 adult flies were subjected to cold diapause and placed in 300 mL bottles with filter paper in their lower section impregnated with 1 mL of 20 percent saccharose in distilled water. Filter paper was also attached to the upper section (lid) to apply the test product OELM. Readings were taken every 3, 6, 12 and 24 h. Results: Results showed that the principal components of the EO are ?-caryophyllene (34.96 percent), germacrene D (25.49 percent) and bicyclogermacrene (9.78 percent). In the insecticide test there was a CL50 for the concentration of 15.14 µg/ml in 3 h exposure, and significant damage to the locomotor system of the flies. Conclusion: The study provides evidence that the EO analyzed is a potential biopesticide(AU)
Subject(s)
Animals , Oils, Volatile , Lantana/toxicity , Insecticides , Diptera , Drosophila melanogaster , BrazilABSTRACT
Introdução: O uso de plantas como inseticidas podem substituir muitos produtos sintéticos por apresentarem baixa toxicidade para os animais e biodegradação no ambiente. A espécie Lantana montevidensis (Spreng.) Briq. (Verbenaceae), chumbinho, é um vegetal subarbustivo rico de compostos secundários para a sua defesa. O modelo experimental com Drosophila melanogaster tem sido usada para estudos, por apresentar vantagens, pois tem fácil manuseio e rápida taxa de reprodução. Objetivo: Avaliar a composição química e efeito inseticida do óleo essencial (OE) de L. montevidensis contra D. melanogaster. Metodos: O OE das folhas secas provenientes do Crato-CE, Brasil, foi extraído por hidrodestilação e foi analisado por CG/EMS para identificação dos constituintes. No ensaio foi avaliada a mortalidade e geotaxia negativa das moscas, em que elas foram expostas a diferentes concentrações do OE (3-30,5 µg/mL do óleo essencial/ar). Um total de vinte moscas adultas foram submetidas à diapausa por meio de resfriamento e em seguidas foram colocadas em frascos de 300 mL, cuja parte inferior havia papel filtro impregnado com 1 mL de sacarose a 20 por cento em água destilada. Na parte superior (tampa) foi afixado um papel filtro para a aplicação do produto a ser testado, nesse caso o OELM. As leituras foram realizadas a cada 3, 6, 12 e 24 h. Resultados: Os resultados mostraram que o OE apresentou o ß-Cariofileno (34,96 por cento), o Germacreno D (25,49 por cento) e o Biciclogermacreno (9, 78 por cento) como componentes majoritários, no ensaio inseticida houve uma CL50 na concentração de 15,14 µg/mL em 3 h de exposição, e houve um efeito significativo nos danos do aparelho locomotor das moscas.mConclusão: Este estudo fornece evidências que esse OE apresenta-se como um potencial bioinseticida(AU)
Introducción: el uso de plantas como insecticidas puede sustituir muchos productos sintéticos porque tienen baja toxicidad para los animales y son fácilmente biodegradables en el medio ambiente. La especie Lantana montevidensis (Spreng.) Briq. (Verbenaceae), Chumbinho, es una planta sub-arbustiva rica en metabolitos secundarios para su defensa. El modelo experimental en Drosophila melanogaster se ha utilizado para varios tipos de estudios, presenta algunas ventajas como: fácil manejo y tasa de reproducción rápida. Objetivo: evaluar la composición química y el efecto insecticida de aceite esencial (OE) de L. montevidensis contra las D. melanogaster. Métodos: el OE de hojas secas del Crato-CE, Brasil, se extrajo por hidrodestilación y se analizó por GC/EMS para identificar los constituyentes. En el test se evaluó la mortalidad y geotaxia negativas de las moscas, donde fueron expuestos a diferentes concentraciones de OE (3-30,5 µg/mL de aceite esencial/aire). Un total de veinte moscas adultas se sometieron a diapausa por enfriamiento y seguido se colocaron en botellas de 300 mL, la parte inferior contenido papel de filtro impregnado con 1 mL de 20 por ciento de sacarosa en agua destilada. En la parte superior (tapa) se haya colocado un papel de filtro para la aplicación del producto a ensayar, la OELM. Las lecturas se realizaron cada 3, 6, 12 y 24 h. Resultados: Los resultados mostraron que el OE presenta la ß-cariofileno (34,96 por ciento), el germacreno D (25,49 por ciento) y bicyclogermacrene (9,78 por ciento) como componentes principales en el ensayo insecticida había una CL50 de la concentración de 15,14 µg/mL en 3 h de exposición, y había un un efecto significativo en el daño del aparato locomotor de las moscas. Conclusión: este estudio proporciona evidencia de que este OE o se presenta como un biopesticida potencial(AU
Introduction: The use of plants as insecticides may be an alternative to many synthetic products because their toxicity to animals is low and they are easily biodegradable in the environment. The species Lantana montevidensis (Spreng.) Briq. (Verbenaceae), chumbinho, is a subshrub rich in secondary metabolites it uses for its own defence. The experimental model for Drosophila melanogaster has been used in several types of studies. Some of its advantages are its easy management and its fast rate of reproduction. Objective: Evaluate the chemical composition and insecticidal effect of the essential oil (EO) of L. montevidensis against D. melanogaster. Method: EO of dry leaves from Crato-CE, Brazil, was extracted by hydrodistillation and analyzed by GC/EMS to identify its constituents. As part of the test, evaluation was conducted or the mortality and negative geotaxis of the flies, to attain which they were exposed to different concentrations of the EO (3-30.5 µg/mL essential oil/air). A total 20 adult flies were subjected to cold diapause and placed in 300 mL bottles with filter paper in their lower section impregnated with 1 mL of 20 percent saccharose in distilled water. Filter paper was also attached to the upper section (lid) to apply the test product OELM. Readings were taken every 3, 6, 12 and 24 h. Results: Results showed that the principal components of the EO are ?-caryophyllene (34.96 percent), germacrene D (25.49 percent) and bicyclogermacrene (9.78 percent). In the insecticide test there was a CL50 for the concentration of 15.14 µg/ml in 3 h exposure, and significant damage to the locomotor system of the flies. Conclusion: The study provides evidence that the EO analyzed is a potential biopesticide(AU)
Subject(s)
Animals , Oils, Volatile , Lantana/toxicity , Drosophila melanogaster , InsecticidesABSTRACT
Cadmium (Cd) is a known hepato- and nephrotoxic pollutant and zinc (Zn) metalloproteins are important targets of Cd. Hence, the administration of Zn may mitigate Cd toxic effects. However, the interaction of Cd and Zn has been little investigated in the brain. Previously, we reported a protective effect of Zn on mortality caused by Cd in rats. Here, we tested whether the protective effect of Zn could be related to changes in brain Zn-proteins, metallothionein (MT) and δ-aminolevulinate dehydratse (δ-ALA-D). Male adult rats were daily administered for 10 days with Zn (2 mg kg-1), Cd (0.25 and 1 mg kg-1) and 0.25 mg kg-1 of Cd plus Zn and 1 mg kg-1 of Cd plus Zn. The body weight loss, food intake deprivation, and mortality occurred in 1 mg kg-1 of Cd, but Zn co-administration did mitigate these effects. The brain Zn content was not modified by treatment with Cd, whereas cerebral Cd levels increased in animals exposed to Cd. The administration of 0.25 mg kg-1 of Cd (with or without Zn) induced lipid peroxidation and decreased MT concentration, but 2 mg kg-1 of Zn and 1 mg kg-1 of Cd did not change these parameters. Brain δ-ALA-D was not modified by Cd and/or Zn treatments. Since the co-administration of Zn did not attenuate the changes induced by Cd in the brain, our results suggest that the protective effect of Zn on impairments caused by Cd in animal status is weakly related to a cerebral interaction of these metals.
ABSTRACT
OBJECTIVE: The aim of this study was to investigate the effect of a single dose of Brazil nuts on the inflammatory markers of healthy individuals. METHOD: A randomized crossover study was conducted with 10 healthy individuals (mean age 24.7 ± 3.4 y). Each individual was tested four times regarding intake of different portions of Brazil nuts: 0, 5, 20 and 50 g. At each testing period, peripheral blood was collected before and at 1, 3, 6, 9, 24, and 48 h after intake of nuts, as well as at 5 and 30 d after intake of various Brazil nut portions. Blood samples were tested for high-sensitivity to C-reactive protein, interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, aspartate and alanine aminotransferases, albumin, total protein, alkaline phosphatase, gamma-glutamyltransferase, urea, and creatinine. RESULTS: Consumption of nuts did not affect biochemical parameters for liver and kidney function, indicating absence of hepatic and renal toxicity. A single intake of Brazil nuts (20 or 50 g) caused a significant decrease in serum IL-1, IL-6, TNF-α, and IFN-γ levels (P < 0.05), whereas serum levels of IL-10 were significantly increased (P < 0.05). CONCLUSION: The results indicate a long-term decrease in inflammatory markers after a single intake of large portions of Brazil nuts in healthy volunteers. Therefore, the long-term effect of regular Brazil nut consumption on inflammatory markers should be better investigated.
Subject(s)
Bertholletia , Cytokines/blood , Inflammation/diet therapy , Nuts , Adult , Biomarkers/blood , Cross-Over Studies , Female , Healthy Volunteers , Humans , Inflammation/blood , Male , Reference Values , Young AdultABSTRACT
Diphenyl diselenide (PhSe)(2) is a synthetic organoselenium compound displaying glutathione peroxidase-like activity. Protective and antioxidant potential of (PhSe)(2) have been extensively investigated in in vivo and in vitro studies. In spite of this, there is a lack of studies addressed to the investigation of potential cytotoxic effect and signaling pathways modulated by this compound. Herein, we aimed to analyze the effects of 24-h treatment with (PhSe)(2) on cell viability and a possible modulation of signaling pathways in human neuroblastoma cell line SH-SY5Y. For this purpose, cells were incubated with (PhSe)(2) (0.3-30 µM) for 24 h and cell viability, apoptotic cell death and modulation of MAPKs (ERK1/2 and p38(MAPK)), and PKC substrates phosphorylation was determined. (PhSe)(2) treatment significantly decreased cell viability and increased the number of apoptotic cells with induction of PARP cleavage. An increase in ERK1/2 phosphorylation was observed at (PhSe)(2) 3 µM. In contrast, higher concentrations of the chalcogenide inhibited ERK1/2, p38(MAPK) and PKC substrate phosphorylation. Pre-treatment with ERK1/2 inhibitor, U0126, increased cell susceptibility to (PhSe)(2). Together, these data indicate a cytotoxic potential of (PhSe)(2) in a neuronal cell line, which appears to be mediated by the ERK1/2 pathway.
Subject(s)
Antioxidants/toxicity , Apoptosis/drug effects , Benzene Derivatives/toxicity , Extracellular Signal-Regulated MAP Kinases/metabolism , MAP Kinase Signaling System/drug effects , Neurons/drug effects , Organoselenium Compounds/toxicity , Benzene Derivatives/agonists , Cell Line, Tumor , Cell Survival/drug effects , Extracellular Signal-Regulated MAP Kinases/chemistry , Humans , Isoenzymes/metabolism , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/chemistry , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/chemistry , Mitogen-Activated Protein Kinase 3/metabolism , Molecular Weight , Neurons/metabolism , Organoselenium Compounds/agonists , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Phosphorylation/drug effects , Poly(ADP-ribose) Polymerases/chemistry , Poly(ADP-ribose) Polymerases/metabolism , Protein Kinase C/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Processing, Post-Translational/drug effects , p38 Mitogen-Activated Protein Kinases/chemistry , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Alloxan is a compound widely used in models of diabetes mellitus due to its ability for damage insulin-producing ß-cells. The aim of this study was to investigate acute (after 24h) and sub-acute (after seven days) effects of 200mg/kg alloxan administration on mice. Biochemical parameters as liver, kidney, and blood δ-ALA-D activity, total sulfhydryl content of hepatic and renal tissues, and hepatic and renal content of malondialdehyde (MDA) were evaluated. The histopathology of hepatic and renal tissues of alloxan-treated and control animals was carried out. Further, blood glucose levels were determined in an attempt to correlate alloxan-induced hyperglycemia with changes in thiol status. Results showed that mice exhibited a significant inhibition of hepatic and renal δ-ALA-D activity in addition to a significant decrease in total sulfhydryl groups of same tissues in both acute and sub-acute alloxan administrations. Moreover, alloxan-induced inhibition of δ-ALA-D activity was partly suppressed when enzymatic assay was performed in the presence of dithiothreitol, suggesting that inhibitory effect of alloxan on δ-ALA-D activity is, at least partially, related to the oxidation of the enzyme's essential thiol groups. Blood δ-ALA-D activity was significantly inhibited only 24h after alloxan administration; however, at this time, a hyperglycemic status was not observed in animals. In contrast, a significant increase in blood glucose levels was observed seven days after alloxan administration. Despite of alterations in biochemical parameters, histological tissue examination of alloxan-treated mice revealed typical renal and hepatic parenchyma. Therefore, these results showed that acute toxic effects of alloxan are related, at least partially, to depletion of sulfhydryl groups, and do not closely relate to the development of hyperglycemia in mice.
Subject(s)
Alloxan/pharmacology , Enzyme Inhibitors/pharmacology , Hyperglycemia/enzymology , Porphobilinogen Synthase/antagonists & inhibitors , Alloxan/chemistry , Animals , Blood Glucose/analysis , Enzyme Activation , Enzyme Inhibitors/chemistry , Hyperglycemia/blood , Hyperglycemia/chemically induced , Hyperglycemia/pathology , Kidney/drug effects , Kidney/enzymology , Kidney/pathology , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/enzymology , Liver/pathology , Male , Malondialdehyde/metabolism , Mice , Molecular Structure , Porphobilinogen Synthase/blood , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
(S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate, a new telluroamino acid derivative, showed remarkable glutathione peroxidase (GPx)-like activity, attesting to its antioxidant potential. However, the stability and toxicity of this compound has not yet been investigated. The present study was designed to investigate the pharmacological/toxicological properties of this compound in vitro and in vivo. In vitro, this telluroamino acid derivative significantly blocked spontaneous and Fe(II)-induced TBARS formation in rat brain homogenates, demonstrating high antioxidant activity. In addition, it exhibited GPx-like and thiol oxidase activities. However, when subcutaneously administered to mice, (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate indicated genotoxic and mutagenic effect in adult male mice. Considering the differential effects of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate in vitro and in vivo, additional experiments are needed to elucidate the mechanism(s) by which this compound displays its antioxidant/toxicological effects.
Subject(s)
Antioxidants/pharmacology , Aspartic Acid/analogs & derivatives , Succinates/pharmacology , Administration, Oral , Analysis of Variance , Animals , Aspartic Acid/toxicity , Comet Assay , DNA Damage , Ferrous Compounds/metabolism , Glutathione Peroxidase/metabolism , Lethal Dose 50 , Male , Mice , Organometallic Compounds/metabolism , Organometallic Compounds/pharmacology , Organometallic Compounds/toxicity , Rats , Rats, Wistar , Succinates/toxicity , Tellurium/metabolism , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Fish oil (FO) supplementation could cause an increase in the concentration of plasmatic free fatty acids and, consequently, could compete with pro-inflammatory arachidonic acid (ARA) derived from brain biomembranes metabolism in the cerebrospinal fluid. Essential fatty acids (EFA) (n-3) have been reported by their antioxidant and neuroprotective properties, and therefore the influence of the FO supplementation on the reserpine-induced motor disorders was studied. Wistar rats were orally treated with FO solution for 5 days, and co-treated with reserpine (R; 1 mg/kg/mL) or its vehicle for 3 days (every other day). Reserpine-induced orofacial dyskinesia and catalepsy (P < 0.05) were prevented by FO (P < 0.05). Biochemical evaluations showed that reserpine treatment increased the lipid peroxidation in the cortex and striatum (P < 0.05), while the FO supplementation prevented this oxidative effect in both brain regions (P < 0.05). Our results showed the protective role of FO in the brain lipid membranes, reinforcing the beneficial effect of n-3 fatty acids in the prevention of degenerative and motor disorders.
