RESUMO
There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTSâ¢+) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH⢠and ABTSâ¢+. On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b achieved significant inflammation inhibition at a lower effective dose 50 (ED50) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen.
Assuntos
Simulação por Computador , Ibuprofeno/química , Ibuprofeno/farmacologia , Silício/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Benzotiazóis/química , Compostos de Bifenilo/química , Domínio Catalítico , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Ibuprofeno/metabolismo , Quelantes de Ferro/química , Quelantes de Ferro/metabolismo , Quelantes de Ferro/farmacologia , Masculino , Simulação de Acoplamento Molecular , Picratos/química , Ratos , Ratos Wistar , Ácidos Sulfônicos/químicaRESUMO
Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20mmol/LAPAP, and necrosis was assessed by LDH leakage. Opuntia robusta had signiï¬cantly higher levels of antioxidants than Opuntia streptacantha. Both extracts signiï¬cantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts signiï¬cantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.
Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Opuntia/química , Fitoterapia , Extratos Vegetais/farmacologia , Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Suplementos Nutricionais , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
The effect of refrigerated 48h transport and 4 days storage on the quality and shelf life of the whole lion's paw scallop Nodipecten subnodosus gonad was evaluated. Proximal composition, adenosine 5´triphosphate (ATP) and related products, K-value, total volatile bases (TVB-N), trimethylamine (TMA-N), pH, fatty acid profile and microbiological analyses were quantified. Gonad holds a significant composition of essential fatty acids while levels of gonadal ATP were initially low; moreover, K-value of the gonad remained constant. With respect to TVB-N and TMA-N, only the former exceeded allowed limits. The pH level showed no significant variation during storage and, despite the high level of TVB-N, according to the TMA-N as well as microbiological analyses it was demonstrated innocuity after 4 days under the transportation and storage conditions utilized.
Avaliou-se o efeito do transporte em refrigeração por 48 horas e quatro dias de armazenamento sobre a qualidade e vida de prateleira da gônada do bivalve pata de leão, Nodipecten subnodosus. Determinou-se a composição centesimal, a adenosina 5'trifosfato (ATP) e afins, o índice K, bases voláteis totais (TVB-N), trimetilamina (TMA-N), pH, perfil de ácidos graxos e análise microbiológica. A Gônada apresentou uma importante composição de ácidos graxos essenciais e baixos níveis iniciais de ATP, enquanto o índice K manteve-se constante. Quanto a TVB -N e TMA- N, apenas as primeiras ultrapassaram os limites admissíveis. Os valores de pH não mostraram nenhuma mudança significativa durante o armazenamento e, apesar dos altos níveis de TVB -N, de acordo com a análise quantitativa e microbiológica TMA- N, a segurança do produto foi demonstrada após quatro dias sob as condições de transporte e armazenamento utilizado.
RESUMO
The effect of refrigerated 48h transport and 4 days storage on the quality and shelf life of the whole lion's paw scallop Nodipecten subnodosus gonad was evaluated. Proximal composition, adenosine 5´triphosphate (ATP) and related products, K-value, total volatile bases (TVB-N), trimethylamine (TMA-N), pH, fatty acid profile and microbiological analyses were quantified. Gonad holds a significant composition of essential fatty acids while levels of gonadal ATP were initially low; moreover, K-value of the gonad remained constant. With respect to TVB-N and TMA-N, only the former exceeded allowed limits. The pH level showed no significant variation during storage and, despite the high level of TVB-N, according to the TMA-N as well as microbiological analyses it was demonstrated innocuity after 4 days under the transportation and storage conditions utilized.(AU)
Avaliou-se o efeito do transporte em refrigeração por 48 horas e quatro dias de armazenamento sobre a qualidade e vida de prateleira da gônada do bivalve pata de leão, Nodipecten subnodosus. Determinou-se a composição centesimal, a adenosina 5'trifosfato (ATP) e afins, o índice K, bases voláteis totais (TVB-N), trimetilamina (TMA-N), pH, perfil de ácidos graxos e análise microbiológica. A Gônada apresentou uma importante composição de ácidos graxos essenciais e baixos níveis iniciais de ATP, enquanto o índice K manteve-se constante. Quanto a TVB -N e TMA- N, apenas as primeiras ultrapassaram os limites admissíveis. Os valores de pH não mostraram nenhuma mudança significativa durante o armazenamento e, apesar dos altos níveis de TVB -N, de acordo com a análise quantitativa e microbiológica TMA- N, a segurança do produto foi demonstrada após quatro dias sob as condições de transporte e armazenamento utilizado.(AU)
Assuntos
Bivalves , Controle de Qualidade , Pectinidae , Prazo de Validade de Produtos , Armazenamento de Alimentos/métodosRESUMO
For many years, several studies have been employing lectin from vegetables in order to prove its toxic effect on various cell lines. In this work, we analyzed the cytotoxic, antiproliferative, and post-incubatory effect of pure tepary bean lectins on four lines of malignant cells: C33-A; MCF-7; SKNSH, and SW480. The tests were carried out employing MTT and 3[H]-thymidine assays. The results showed that after 24 h of lectin exposure, the cells lines showed a dose-dependent cytotoxic effect, the effect being higher on MCF-7, while C33-A showed the highest resistance. Cell proliferation studies showed that the toxic effect induced by lectins is higher even when lectins are removed, and in fact, the inhibition of proliferation continues after 48 h. Due to the use of two techniques to analyze the cytotoxic and antiproliferative effect, differences were observed in the results, which can be explained by the fact that one technique is based on metabolic reactions, while the other is based on the 3[H]-thymidine incorporated in DNA by cells under division. These results allow concluding that lectins exert a cytotoxic effect after 24 h of exposure, exhibiting a dose-dependent effect. In some cases, the cytotoxic effect is higher even when the lectins are eliminated, however, in other cases, the cells showed a proliferative effect.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Phaseolus/química , Lectinas de Plantas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/toxicidade , Fatores de TempoRESUMO
Plants belonging to the genus Opuntia spp. are the most abundant of the Cactaceae family, grown throughout America and the Mediterranean central area. Its fruit, known as cactus pear or prickly pear, is an oval berry grouped in different colors. Some studies have shown its antioxidant activities which may help in preventing chronic pathologies such as diabetes. The purpose of the study was to evaluate the antioxidant capacity of three varieties of prickly pear juice (red-purple, white-green and yellow-orange) in five different concentrations (100, 250, 500, 750, and 1000 mg/mL) by DPPH (1,1-diphenyl-2-picrylhydrazyl radical) colorimetric method, selecting the best variety to determine its anticlastogenic potential against methyl methanesulfonate (MMS). The results indicate that the highest antioxidant was found in the juice of the prickly pear red-purple variety (PPRP), in all concentrations. Its anticlastogenic potential was therefore evaluated with a micronucleus assay. The experiment was run over two weeks. A negative control was included along with a positive control with MMS (40 mg/kg), a group of mice treated with PPRP (25 mL/kg), and three groups with PPRP (in doses of 25, 16.5 and 8.3 mL/kg) plus the mutagen. The PPRP was administered daily by oral gavage and the MMS was injected intraperitoneally five days prior to the end of the experiment. Blood samples were obtained at 0, 24, 48, 72 and 96 h in order to determine the frequency of micronucleated polychromatic erythrocytes (MNPE). The results indicated that PPRP is not a genotoxic agent, on the contrary, it may reduce the number of MNPE. In this regard, the PPRP showed an anticlastogenic effect directly proportional to its concentrations. Thus, the highest protection was obtained with a concentration of 25 mL/kg after 48 h of treatment.
Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Frutas/química , Opuntia/química , Extratos Vegetais/farmacologia , Animais , Bebidas , Dano ao DNA/efeitos dos fármacos , Eritrócitos , Masculino , Camundongos , Testes para MicronúcleosRESUMO
The in vitro antioxidant activities of eight 3-carboxycoumarin derivatives were assayed by the quantitative 1,1-diphenyl-2-picrylhydrazil (DPPHâ¢) radical scavenging activity method. 3-Acetyl-6-hydroxy-2H-1-benzopyran-2-one (C1) and ethyl 6-hydroxy-2-oxo-2H-1-benzopyran-3-carboxylate (C2) presented the best radical-scavenging activity. A quantitative structure-activity relationship (QSAR) study was performed and correlated with the experimental DPPH⢠scavenging data. We used structural, geometrical, topological and quantum-chemical descriptors selected with Genetic Algorithms in order to determine which of these parameters are responsible of the observed DPPH⢠radical scavenging activity. We constructed a back propagation neural network with the hydrophilic factor (Hy) descriptor to generate an adequate architecture of neurons for the system description. The mathematical model showed a multiple determination coefficient of 0.9196 and a root mean squared error of 0.0851. Our results shows that the presence of hydroxyl groups on the ring structure of 3-carboxy-coumarins are correlated with the observed DPPH⢠radical scavenging activity effects.
Assuntos
Cumarínicos/farmacologia , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/farmacologia , Algoritmos , Benzopiranos/síntese química , Benzopiranos/farmacologia , Compostos de Bifenilo/química , Biologia Computacional , Cumarínicos/síntese química , Cumarínicos/química , Modelos Teóricos , Picratos/química , Relação Quantitativa Estrutura-AtividadeRESUMO
In vitro antioxidant activity for 12 stannoxanes derived from Ph(3)SnCl (compounds 1-3), Ph(2)SnCl(2) (compounds 4-6), Bu(3)SnCl (compounds 7-9), and Bu(2)SnCl(2) (compounds 10-12), was assayed qualitatively by the chromatographic profile with 1,1-diphenyl-2-picrylhydrazil (DPPH) method and by two quantitative methods: the DPPH radical scavenging activity and Ferric-Reducing Antioxidant Power (FRAP) assays. The results were compared with those obtained with the starting materials 2-pyridine- carboxylic acid (I), 3-pyridinecarboxylic acid (II) and 4-pyridinecarboxylic acid (III), as well as with standard compounds, such as vitamin C and vitamin E, respectively. The in vitro antiradical activity with DPPH of diphenyltin derivative 5 showed a very similar behavior to vitamin C at a 20 microg/mL concentration, whereas according to the FRAP method, compound 8 was better. This difference is due to the mechanism of the antioxidant process. The Structure-Activity Relationships (SAR) for both methods is also reported.