RESUMO
The present study reports a simple two-step method for the synthesis of arylselanyl hydrazide derivatives using hypophosphorous acid and polyethylene glycol (H3 PO2 /PEG-400) as an alternative reducing system and hydrazine hydrate (NH2 NH2 â xH2 O/50-60 %). This single-vessel procedure was employed with methyl acrylate 2a and methyl bromoacetate 2b using diaryl diselenides to generate the nucleophile species to produce, respectively, 3-(arylselanyl)propane-hydrazides 4a-e and 2-(arylselanyl)acetohydrazides 5a-e with good yields by accelerating the reduction of -Se-Se- bond, when compared to available methods. The synthesized molecules are structurally similar to the isoniazid (INH). Therefore, we perform inâ silico molecular docking studies, using the lactoperoxidase enzyme, in order to verify whether the INH Se derivatives could interact in a similar way to INH at the active site of the mammalian enzyme. The inâ silico results indicated a similar type of interaction of the arylselanyl hydrazide derivatives with that of INH. In view of the similar inâ silico interaction of the selenium derivatives of INH, the arylselanyl hydrazide derivatives reported here should be tested against Mycobacterium tuberculosis inâ vitro.
Assuntos
Antituberculosos , Mycobacterium tuberculosis , Animais , Hidrazinas , Isoniazida/química , Isoniazida/farmacologia , Mamíferos , Simulação de Acoplamento MolecularRESUMO
African eggplant (Solanum macrocarpon L) (AE) and Black Nightshade (Solanum nigrum L) (BN) leaves are green leafy vegetables with nutritional and ethnobotanical values. We have previously characterized the vegetables via HPLC/LC-MS to reveal notable phenolic acids, flavonoids and alkaloids. In this present study, we addressed the efficacy of the two vegetables in mitigating mercuric chloride (HgCl2)-induced neurotoxicity and memory impairment in Drosophila melanogaster. Flies were exposed to HgCl2 (0.30 mg/g) alone or in combination with the vegetables (0.1 and 1.0%) of both samples in their diets for seven days. The results showed that HgCl2 (Hg)-exposed flies had significantly reduced survival rate and memory index, which were ameliorated in the Hg-exposed flies fed AE or BN. This was accompanied by increased reactive oxygen species (ROS) levels, reduced total thiol, as well as catalase, glutathione transferase (GST) and acetylcholine esterase (AChE) activities in Hg-exposed fly heads, but ameliorated in Hg-exposed flies fed dietary inclusions of the vegetables. In addition, the Hg-induced alterations in SOD, NF-ÒB/Relish, Dronc and Reaper mRNA levels were statistically indistinguishable from controls in Hg-treated flies fed diets containing AE or BN. Normalization of cnc/Nrf2 and FOXO were observed only in Hg-treated flies fed BN. These findings suggest that dietary AE or BN leaves offer protection against Hg-induced memory impairment and neurotoxicity in D. melanogaster, and further justify them as functional foods with neuroprotective properties.
Assuntos
Solanum nigrum , Solanum , Animais , Antioxidantes/farmacologia , Drosophila melanogaster , Oxirredução , Estresse Oxidativo , VerdurasRESUMO
BACKGROUND: This study investigated the modulatory capacity of two Solanum green leafy vegetables; S. macrocarpon L. (African eggplant AE) and S. nigrum L. (Black nightshade BN) on dysregulation of some antioxidant, pro-apoptotic, pro-inflammatory-like, acetylcholinesterase gene expression and redox status in the Drosophila melanogaster model of aluminum-induced neurotoxicity. METHODS: Flies were exposed to AlCl3 (6.7â mM) alone or in combination with the leaves (0.1 and 1.0%) from both samples in their diet for seven days. Thereafter, the fly heads were rapidly separated, homogenized, and used to assay for reactive oxygen species (ROS), total thiol content, catalase, glutathione-S-transferase (GST), acetylcholinesterase (AChE) activities, and the expression of antioxidant-mediators (Hsp70, catalase, cnc/Nrf2, Jafrac1 and FOXO), acetylcholinesterase (Ace1), pro-apoptotic caspase-like (Dronc) and its regulator (reaper), as well as inflammation-related (NF-kB/Relish) genes. RESULTS: Results showed that AlCl3-exposed flies had significantly reduced survival rate which were ameliorated by AlCl3 also elevated ROS, GST and reduced AChE activities in fly heads while dietary inclusions of AE and BN ameliorated survial rate and oxidative stress in AlCl3-exposed flies. In addition, Hsp70, Jafrac1, reaper and NF-kÒB/Relish were significantly upregulated in AlCl3-exposed fly heads, while cnc/Nrf2 and FOXO were significantly downregulated, but catalase, Dronc and Ace were, not significantly modulated. Nevertheless, these impairments in gene expression levels were ameliorated by dietary inclusions of AE and BN during AlCl3 exposure. CONCLUSION: These findings showed that dietary inclusions of AE and BN leaves offer protection against Al-induced neurotoxicity in D. melanogaster and thus, could serve as functional foods with neuroprotective properties.
Assuntos
Síndromes Neurotóxicas , Solanum nigrum , Solanum , Acetilcolinesterase/metabolismo , Alumínio/metabolismo , Animais , Antioxidantes/metabolismo , Caspases/genética , Caspases/metabolismo , Catalase/genética , Catalase/metabolismo , Dieta , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Solanum/metabolismo , Solanum nigrum/metabolismo , Compostos de Sulfidrila/metabolismo , VerdurasRESUMO
This article presents the statistical analysis data from Drosophila melanogaster development (from larvae to adult) and learning and memory retention behavior of a Pavlovian conditioning in male and female flies exposed to copper. While the full data sets are available In the article: Copper decrease associative learning and memory in D. melanogaster, this data-in-brief article includes the detailed statistical analysis performed. Data demonstrates Statistica Software analysis between the subject part of the analysis: 2 treatments x 2 sexes x 2 ages and within subject part of the analysis: 2 treatments x 2 sex x 2 ages x 4 times, repeated measures.
RESUMO
ETNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels is a plant widely used in folk medicine to treat diabetes mellitus (DM). The tea from its leaves is frequently used by diabetics for lowering hyperglycemia. There is a close relationship between DM and atherosclerosis, a chronic immuno-inflammatory disease, were the early stages encompass oxidative and glycative modifications in the structure of low density lipoprotein (LDL). AIM OF THIS STUDY: To investigate the potential protective effects of aqueous-leaf extract from Syzygium cumini (S.cExt) against CuSO4-induced oxidation and methylglyoxal (MG)-induced glycation of human LDL in vitro. MATERIALS AND METHODS: LDL oxidative changes were evaluated by measuring conjugated dienes (CD) formation, thiobarbituric acid reactive substances (TBARS) levels, quenching of tryptophan (Trp) fluorescence and structural modifications in LDL particle. In LDL glycated by MG (glyLDL), we determined the levels of fluorescent advanced glycation end products (AGEs) and mobility by agarose gel electrophoresis. RESULTS: S.cExt blocked oxidative events induced by CuSO4 in human LDL, plasma and serum. Fourier transform infrared spectroscopy (FT-IR) revealed that specific regions of apoB100 were oxidized by CuSO4 in human LDL and that S.cExt reduced these oxidations. Unlike, the increased AGEs levels and eletrophoretic mobility observed in LDL MG-glycated were not modified by S.cExt. CONCLUSION: The findings herein indicate that S.cExt could be tested in atherogenesis models as potential protective agent against LDL oxidation.
Assuntos
Lipoproteínas LDL/metabolismo , Extratos Vegetais/farmacologia , Syzygium/química , Apolipoproteína B-100/metabolismo , Sulfato de Cobre/administração & dosagem , Eletroforese em Gel de Ágar , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Medicina Tradicional , Oxirredução , Folhas de Planta , Espectroscopia de Infravermelho com Transformada de Fourier , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The present study was designed to investigate the mineral content and antimicrobial activity of Curcuma Longa extracts and its essential oil. We also determined the lipid peroxidation inhibition activity of the ethanolic extract against sodium nitroprusside (SNP) induced thiobarbituric acid reactive species (TBARS) formation in rat's brain, kidney and liver homogenates. Major constituents of essential oil identified by gas chromatography and mass spectrometry (GCMS) were beta-sesquiphellandrene (38.69%), alpha-curcumene (18.44%) and p-mentha-1,4 (8)-diene (16.29%). Atomic absorption spectroscopy (AAS) was used for the quantitative estimation of Calcium (Ca), Magnesium (Mg), Iron (Fe), Copper (Cu), Zinc (Zn), Chromium (Cr), Nickel (Ni) and Manganese (Mn). The extract showed highest Mg (49.4 mg/l) concentration followed by Ca (35.42 mg/l) and Fe (1.27 mg/l). Our data revealed that the ethanolic extract of Curcuma Longa at 1-10 mg/kg significantly inhibited TBARS production in all tested homogenates. Crude extracts and essential oil were tested against three gram positive bacteria i.e. Bacillus subtilis, Bacillus atrophoeus, Staphylococcus aureus, six gram negative bacteria i.e. Escherichia coli, Klebsiella pneumonias, Salmonella typhi, Pseudomonas aeruginosa, Erwinia carotovora, Agrobacterium tumefaciens and one fungal strain namely Candida albicans by disc diffusion assay. Essential oil showed highest anti-microbial activity as compared to the crude extracts. The present study confirms the significant antimicrobial and antioxidant potential of the studied plant, which can be considered as a diet supplement for a variety of oxidative stress induced or infectious diseases.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Curcuma/química , Cromatografia Gasosa-Espectrometria de Massas , Peroxidação de Lipídeos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Anti-Infecciosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Relação Dose-Resposta a Droga , Etanol/química , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Nitroprussiato/farmacologia , Óleos Voláteis/isolamento & purificação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Óleos de Plantas/isolamento & purificação , Plantas Medicinais , Solventes/química , Espectrofotometria Atômica , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The study describes the effect of ethanolic extract of Nigella sativa against Fe(II) induced lipid peroxidation. Basal and Fe(II) induced thiobarbituric acid reactive species (TBARS) production was significantly inhibited by the ethanolic extract of Nigella sativa at 25-200 µg/ml. Our data revealed that the extract has high DPPH radical scavenging activity at highest tested concentrations. The extract significantly chelated Fe(II) and scavenged hydroxyl (OH) radical at 25-200µg/ml concentration. The nutritional analysis was performed and carbohydrate, fats, fiber, protein, moisture and ash content were measured in the studied extract. The phytochemical analysis confirmed the presence of alkaloid, carbohydrate & sugar, glycosides, phenolic compounds, flavonoids, protein and amino acid, phytosterols, tannins, gum and mucilage. The extract also showed significant antimicrobial activities against 10 bacterial strains i.e. Salmonella typhi, Bacillus subtilis, Bacillus cereus, Klebsiella pneumonia, Escheria coli, Xanthomonas, Salmonella heidelberg, Staphylococcus aureus, Clostridium and Escheria coli (human) and 5 fungal strains i.e. Aspergillus niger, Entomola, Aspergillus flavus, Alternaria alternata and Penicillium. This study confirms the potential antioxidant and antimicrobial activities of ethanolic extract of Nigella sativa which can be considered not only as a diet supplement but can be used against a variety of free radical induced damage diseases.
Assuntos
Encéfalo/efeitos dos fármacos , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nigella sativa/química , Extratos Vegetais/farmacologia , Animais , Encéfalo/metabolismo , Etanol , Rim/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Diabetic status is associated with an increase on oxidative stress markers in humans and animal models. We have investigated the in vitro effects of high concentrations of glucose on the profile of oxidative stress and osmotic fragility of blood from control and diabetic patients; we considered whether its antioxidant properties could afford some protection against glucose-induced osmotic fragility, and whether ebselen could act as an inhibitor of hemoglobin glycation. Raising blood glucose to 5-100 mmol/L resulted in a concentration-dependent increase of glycated hemoglobin (HbA1c; P < 0.001) and thiobarbituric acid reactive species (TBA-RS) content (P < 0.004). Non-protein SH groups (NPSH) also increased significantly as the concentration of glucose increased up to 30 mmol/L (P < 0.001). The osmotic fragility was more pronounced in blood of uncontrolled diabetic patients than in these non-diabetic subjects. Ebselen significantly reduced the glucose-induced increase in osmotic fragility and inhibited HbA1c formation (P < 0.0001). These results indicate that blood from patients with uncontrolled diabetes are more sensitive to osmotic shock than from patients with controlled diabetes and control subjects in relation to increased production of free radicals in vivo.
Assuntos
Antioxidantes/farmacologia , Azóis/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glucose/toxicidade , Compostos Organosselênicos/farmacologia , Diabetes Mellitus Tipo 2/sangue , Glicosilação/efeitos dos fármacos , Humanos , Isoindóis , Fragilidade Osmótica/efeitos dos fármacos , Fragilidade Osmótica/fisiologiaRESUMO
In this study we have examined the in vivo toxic effects of various organochalcogens on hepatic, renal, glycemic and lipid profile. Diorganotellurium dichloride phosphonate (C1) at all tested doses did not modify serum alanine aminotransferase (ALT) activity in mice. While, 2-butyltellurium furan (C2) and dinaphthalene ditelluride (C3) at a dose of 0.75 and 0.125 mmol/kg caused an increase in aspartate aminotransferase (AST) and ALT activities. Our data showed that C1 caused an increase in urea content at different doses while treatment with C2 and C3 did not modify urea content. Treatment with C2 caused a significant alteration in serum glucose and fructosamine levels which explains the possible toxicity of these compounds. No significant changes were observed for cholesterol and triglycerides levels. These results suggest that organochalcogen compounds presented liver and renal toxicity and also altered glycemic profile which may leads to various clinical complications.
Assuntos
Compostos Organometálicos/toxicidade , Telúrio/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Creatinina/sangue , Relação Dose-Resposta a Droga , Frutosamina/sangue , Hemoglobinas/metabolismo , Testes de Função Renal , Lipídeos/sangue , Testes de Função Hepática , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Análise de SobrevidaRESUMO
Sepsis is a potentially deadly complication that can be caused by different factors. Actually, it is known that oxidative stress is involved in the pathogenesis of sepsis. Thus, the aim of this study was to evaluate the effect of diphenyl diselenide (PhSe)(2), an emergent compound, on oxidative stress parameters induced by sepsis in rats. Animals were pre-injected with (PhSe)(2) or vehicle. Twenty-four hours later, sepsis was induced by cecal ligation puncture (CLP). After 12 h, liver was taken for thiobarbituric acid reactive species (TBARS) measurement, δ-aminolevunic acid dehydratase (δ-ALA-D), Cu/Zn superoxide dismutase (Cu/Zn SOD) and catalase (CAT) activities assay. The sepsis increased TBARS, inhibited δ-ALA-D, activated Cu/Zn SOD and had a tendency to decrease CAT activity. However, (PhSe)(2) prevented the TBARS formation, but did not prevent the inhibition of δ-ALA-D activity in the animals with damage. Thus, this study showed that (PhSe)(2) partially prevents the oxidative stress induced by sepsis, indicating the potential of this compound as a treatment for this pathology. Nevertheless, more tests should be performed to confirm the hypothesis suggested here.
Assuntos
Antioxidantes/farmacologia , Derivados de Benzeno/farmacologia , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Catalase/metabolismo , Ceco/lesões , Modelos Animais de Doenças , Ligadura , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Sintase do Porfobilinogênio/metabolismo , Ratos , Ratos Wistar , Sepse/metabolismo , Sepse/patologia , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Acute pulmonary embolism (APE) is a major cause of pulmonary hypertension and death. We examined the effects of sildenafil on the hemodynamic changes caused by APE in anesthetized dogs. Sham-operated dogs (n = 3) received only saline. APE was induced by stepwise IV injections of 300 mum microspheres in amounts adjusted to increase mean pulmonary artery pressures by 20 mm Hg. Hemodynamic evaluation was performed at baseline, after APE was induced, and then after sildenafil 0.25 mg/kg (n = 8), or sildenafil 1 mg/kg + 0.3 mg . kg(-1) . h(-1) (n = 8) or saline (n = 9) infusions were started. Similar experiments were conducted to examine the effects of sildenafil in rat isolated perfused lung preparation. Plasma thiobarbituric acid reactive species were also determined in both studies to measure oxidative stress. Both doses of sildenafil reduced mean pulmonary artery pressures in dogs by approximately 8 to 16 mm Hg (both P < 0.05) and attenuated the increase in oxidative stress after APE. Mean arterial blood pressure remained unaltered after both doses of sildenafil. Sildenafil produced similar effects after APE in rat isolated perfused lung preparation. These findings indicate that IV sildenafil can selectively attenuate the increases in mean pulmonary artery pressures after APE, possibly through antioxidant mechanisms.