RESUMEN
Newcastle disease virus (NDV) causes huge economic loss to the poultry industry due to high mortality and morbidity. The present study aimed to assess the protective role of novel phosphorylated analogue ABC-1 in vivo in NDV-infected chickens through the inhibition of fusion protein. Both NDV-induced oxidative damage and protective role of novel phosphorylated ABC-1 were evaluated in vital organs such as the liver and lung of chickens. Enzyme linked immunosorbent assay (ELISA) results showed that protein oxidation and nitration levels were significantly raised in NDV-infected tissues compared to healthy controls, whereas these levels were reduced significantly (P < 0.05) in birds treated with phosphorylated compounds compared to the NDV-infected group alone. Additional investigation with double immunofluorescence showed that the large amount of immuno colocalization and Western blot analysis also confirmed this observation through its band pattern in NDV-infected birds compared to healthy birds, whereas these alterations were reduced in treatment with novel phosphorylated ABC-1. The expression of fusion glycoprotein was studied by immuno colocalization, PCR, and flow cytometry, and results demonstrated that the novel phosphorylated analogues reduced the expression of fusion glycoprotein. These results put forth that novel phosphorylated ABC-1 protects chickens from NDV-induced pathogenesis, protein oxidation/nitration, and exerts potent antiviral activity.
Asunto(s)
Fármacos Anti-VIH/farmacología , Didesoxinucleósidos/farmacología , Virus de la Enfermedad de Newcastle/efectos de los fármacos , Animales , Pollos , Pruebas de Sensibilidad Microbiana , FosforilaciónRESUMEN
Green synthesis of selenium nanoparticles (SeNPs) was achieved by a simple biological procedure using the reducing power of fenugreek seed extract. This method is capable of producing SeNPs in a size range of about 50-150 nm, under ambient conditions. The synthesized nanoparticles can be separated easily from the aqueous sols by a high-speed centrifuge. These selenium nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and elemental analysis by X-ray fluorescence spectrometer (XRF). Nanocrystalline SeNPs were obtained without post-annealing treatment. FTIR spectrum confirms the presence of various functional groups in the plant extract, which may possibly influence the reduction process and stabilization of nanoparticles. The cytotoxicity of SeNPs was assayed against human breast-cancer cells (MCF-7). It was found that SeNPs are able to inhibit the cell growth by dose-dependent manner. In addition, combination of SeNPs and doxorubicin shows better anticancer effect than individual treatments.
Asunto(s)
Doxorrubicina/administración & dosificación , Tecnología Química Verde/métodos , Nanopartículas del Metal/química , Nanomedicina/métodos , Neoplasias/tratamiento farmacológico , Extractos Vegetales/química , Selenio/administración & dosificación , Trigonella/química , Antibióticos Antineoplásicos/química , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Femenino , Humanos , Células MCF-7 , Microscopía Electrónica de Rastreo , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
CONTEXT: Black mustard [Brassica nigra (L.) Koch] of the Brassicaceae (Cruciferae) family is commonly used as a spice and a cheap source of antimicrobial agents for bacterial infections. OBJECTIVES: The present investigation was to demonstrate the protective effect of the methanol extract of B. nigra leaves against D-galactosamine (D-GalN)-induced hepatic and nephrotoxicity in Wistar rats. METHODS: Activity of the methanol extract of B. nigra at doses of 200 and 400 mg/kg b.wt. against D-GalN (500 mg/kg b.wt.) induced toxicity, with silymarin used as the standard. Histological damage, activities of serum marker enzyme, hematological changes, metabolites such as bilirubin, urea, uric acid, and creatinine levels, tissue thiobarbutric acid reactive substance, enzymic and non-enzymic antioxidants and inflammatory marker enzymes such as myeloperoxidase, cathepsin D, and acid phosphatase were assessed. RESULTS: The D-GalN-induced toxicity was evident from a significant increase (p < 0.001) in the serum and tissue inflammatory markers in toxic rats, when compared with the control (saline alone treated animals). The B. nigra pretreated groups (200 and 400 mg/kg b.wt.) showed significant (p < 0.001) reduction in the D-GalN-induced toxicity as obvious from biochemical parameters. Histopathological observations confirm the protective effect of B. nigra leaf extract by reduction in hepatic and renal tissue damage. Experimentals extract showed a similar effect as the standard. CONCLUSIONS: The crude methanol extract of B. nigra leaf lacks inherent toxicity and exhibits hepatic and nephroprotective effects against D-GalN-induced toxicity in Wistar rats.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedades Renales/prevención & control , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Planta de la Mostaza , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citoprotección , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Galactosamina , Mediadores de Inflamación/sangre , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/sangre , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Hígado/metabolismo , Hígado/patología , Metanol/química , Planta de la Mostaza/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Hojas de la Planta , Plantas Medicinales , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/toxicidad , Ratas , Ratas Wistar , Silimarina/farmacología , Solventes/químicaRESUMEN
Cigarette smoking is a major risk factor for cardiovascular diseases and exerts negative effects on the lipid profile. This study was aimed to evaluate the preventive role of (-)-epigallocatechin-gallate (EGCG) on lipid metabolism and cardiac inflammatory changes in cigarette smoke (CS) induced myocardial dysfunction. Adult male albino rats were exposed to side stream CS for a period of 12 weeks and simultaneously administered with EGCG (20 mg/kg b.w./day, p.o.). Exposure to CS showed significant increased (P < 0.05) activities of cardiac injury markers such as, creatine kinase-MB (CKMB) and lactate dehydrogenase (LDH) in serum and subsequent decrease in these enzyme activities in heart. A significant increase (P < 0.05) in serum total cholesterol, fatty acids, phospholipids, and triglycerides were observed in CS exposed rats, along with elevated low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol and decreased high density lipoprotein (HDL) cholesterol. In myocardium, total cholesterol, fatty acids and triglycerides were increased, whereas the phospholipids were found to be decreased. Cardiac lecithin: cholesterol acyl trasferase (LCAT), lipoprotein lipase (LPL), and plasma LCAT activities were significantly decreased (P < 0.05) on CS exposure. Supplementation of EGCG reverted the cardiac injury markers, abnormalities of lipid profile, and lipid-metabolizing enzymes in serum and myocardium. Western blot analysis showed a significant increase in protein expression levels of nuclear factor kappa-B (NF-κB), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in heart of CS exposed rats. EGCG-treated rats showed a significant decrease in the expression of inflammatory markers. Our data suggest that chronic CS causes lipidemic anomalies and cardiac inflammatory aberrations which may promote cardiac dysfunction and that the antioxidant EGCG exerts a cardio protective effect via reduction of oxidative stress.
Asunto(s)
Antioxidantes/farmacología , Catequina/análogos & derivados , Corazón/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Miocarditis/inducido químicamente , Miocardio/patología , Animales , Catequina/farmacología , Colesterol/sangre , Creatina Quinasa/sangre , Ciclooxigenasa 2/metabolismo , Isoenzimas/sangre , L-Lactato Deshidrogenasa/sangre , Lípidos/sangre , Masculino , Miocarditis/metabolismo , Miocarditis/prevención & control , Miocardio/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Wistar , Fumar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
CONTEXT: Vernonia cinerea (L.) Less [Compositae (Asteraceae)] is used traditionally for several medical purposes such as inflammation, pain, fever, and cancer. OBJECTIVES: The present study identified the bioactive constituents in the methanol extract of Vernonia cinerea leaf and evaluated its antioxidant activity and acute toxicity. METHODS: The identification of phytochemicals was accomplished by GC-MS and the major antioxidant phenolic compounds in the extract were quantified by HPTLC analysis. To quantify the essential elements, atomic absorption spectrophotometeric analysis was carried out. Total phenol and flavonoid content was measured by Folin-Ciocalteau reagent and 2% aluminium chloride, respectively. RESULTS: GC-MS analysis identified the presence of 27 phytoconstituents. The predominant phenolic compound in the extract as quantified by HPTLC was gallic acid (1.92 mg/g) followed by rutin (0.705 mg/g), quercetin (0.173 mg/g), caffeic acid (0.082 mg/g) and ferulic acid (0.033 mg/g). The following elements were quantified: Fe (0.050 ppm), Mn (0.022 ppm), Co (0.0180 ppm), Pb (0.029 ppm), Hg (3.885 ppm) and Se (4.5240 ppm). The antioxidant activity of the extract increased with increasing concentration and the correlation (r²) for all in vitro assays were satisfactory. CONCLUSIONS: V. cinerea extract has significant (p < 0.05) antiradical activity. Hence, V. cinerea may have potential medicinal value and can be used in the formulation of pharmacological products for degenerative diseases.
Asunto(s)
Antioxidantes/farmacología , Asteraceae/química , Asteraceae/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Cromatografía en Capa Delgada , Depuradores de Radicales Libres/química , Cromatografía de Gases y Espectrometría de Masas , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Modelos Lineales , Hígado/patología , Metanol , Minerales/análisis , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Ratas , Ratas Wistar , Solventes , Espectrofotometría Atómica , Espectrofotometría UltravioletaRESUMEN
One of the pivotal mechanisms projected for bioflavonoids in cancer chemoprevention is through their intervention against mutagen-DNA interaction. Recent literatures emphasize the role of troxerutin (TXER) as an emerging anticancer agent. However, there are no reports on its intervention in any carcinogen-DNA interaction. The present study investigates the possibility of TXER, in prevention of 2-aminoanthracene (2-AA) contact with DNA. Steady state and time resolved fluorescence spectroscopy results, highlight the direct contact of 2-AA with DNA, while presence of TXER prevented this interaction. Gel-electrophoresis study clearly revealed that, TXER inhibits 2-AA+UVA radiation induced DNA damage. Fluorescence microscopic studies elucidated that, TXER treatment obstructs the 2-AA interaction with cellular DNA, while molecular docking showed the energetically favourable structure of TXER/2-AA/TXER complex. Further anti-mutagenicity experiment revealed that, TXER prevents the mutation induced colony formation in mutant strain of S. typhymurium. Our in vitro and ex vivo experimental findings provide imperative evidence about the protective role of TXER against environmental carcinogens through the inhibition of carcinogen-DNA interaction, implicating its potential for therapeutic applications in cancer.
Asunto(s)
Antracenos/toxicidad , Antimutagênicos/farmacología , ADN/efectos de los fármacos , Hidroxietilrutósido/análogos & derivados , Mutágenos/toxicidad , Células 3T3 , Animales , Daño del ADN/efectos de los fármacos , Genotipo , Hidroxietilrutósido/farmacología , Ratones , Modelos Moleculares , Simulación del Acoplamiento Molecular , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Sophora/química , Rayos UltravioletaRESUMEN
Despite zinc oxide nanoparticles (ZnONPs) being increasingly used as carriers in biomedical fields due to their multifaceted properties and therapeutic importance, better understanding of the mechanisms and cellular consequences resulting from their interaction with cells and cellular components has been warranted. In the present study, we investigate the size-dependent interaction of ZnONPs on RBCs, and its impact on cell viability, DNA damage, ROS generation and morphological changes, employing cellular and analytical methods. Size, charge, stability and solubility were confirmed by DLS, zeta potential, ICP-AES and TEM analysis. Further ICP-AES, TEM, spectroscopic observations and cell based assays showed that ZnONPs exhibited a size dependent impact on RBCs and haemoglobin (Hb), particularly size <50 nm. Conversely, ferulic acid (FA) conjugates and serum albumin significantly reduced the adverse effects exhibited by ZnONPs. The extent of DNA damage and ROS generation is comparatively low in ZnONPs-FA than in ZnONPs alone treated cells. Thus our study documents a novel conceptualization delineating the influence of size on the material properties and therapeutic potential of nanoparticle.
Asunto(s)
Ácidos Cumáricos/farmacología , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Nanopartículas/toxicidad , Tamaño de la Partícula , Óxido de Zinc/toxicidad , Albúminas/metabolismo , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Eritrocitos/citología , Eritrocitos/ultraestructura , Hemoglobinas/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Solubilidad , Espectrometría de Fluorescencia , Espectrometría RamanRESUMEN
The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and anti-tumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin-C (MMC)--using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.
Asunto(s)
Antineoplásicos/efectos adversos , Células de la Médula Ósea/efectos de los fármacos , Crocus/química , Daño del ADN , Sustancias Protectoras/uso terapéutico , Administración Oral , Animales , Antineoplásicos/administración & dosificación , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa , Inyecciones Intraperitoneales , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacologíaRESUMEN
Increased levels of environmental pollutants are linked to almost all human disorders; the efficient method to manage the human health is through naturally available dietary molecule. Solanum torvum (ST) Swartz (Solanaceae) commonly called Turkey Berry is found in Africa, Asia, and South America. Its fruit, part of traditional Indian cuisine, is a widely consumed nutritious herb, acclaimed for its medicinal value. ST aqueous extract (STAe) (250, 500, and 1000 mg/kg b.w., 6 days; oral) against acute Cadmium (Cd) (6.3 mg/kg b.w., single dose; oral) toxicity was evaluated in rats. Protective effect was assessed using serum markers, tissue antioxidants, oxidant derivatives, glycoprotein, and histopathological studies. The activities of serum marker enzymes were increased (40-60 %); antioxidant enzymes such as SOD and CAT, GSH, and its metabolic enzyme activities were decreased (50-80 %) in the liver and kidney upon Cd intoxication. During STAe pre-treatment, at doses of 250 and 500 mg/kg b.w., the above changes were brought to near normal (25-63 %). Tissue 4-hydroxynonenal, 3-nitrotyrosine, and protein carbonyls were increased (8-15 fold) in Cd-alone-treated rats, whereas pre-supplementation of STAe significantly decreased their levels and inhibited the protein glycosylation effectively. The pharmacological effect of STAe was confirmed by histopathological observations. Based on previous literature and present investigation, we conclude that ST may serve as a potential functional food against environmental contaminant such as heavy metal-induced oxidative stress.
Asunto(s)
Cadmio/toxicidad , Frutas/química , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Solanum/química , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Contaminantes Ambientales/toxicidad , Glicosilación/efectos de los fármacos , Riñón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas Wistar , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
The process of human islet isolation triggers a cascade of stressful events in the islets of Langerhans involving activation of apoptosis and necrosis and the production of proinflammatory molecules that negatively influence islet yield and function and may produce detrimental effects after islet transplantation. In this study, we showed that activation of nuclear factor-kappaB (NF-kappaB) and poly(ADP-ribose) polymerase (PARP), two of the major pathways responsible for cellular responses to stress, already occurs in pancreatic cells during the isolation procedure. NF-kappaB-dependent reactions, such as production and release of interleukin-6 and -8 and macrophage chemoattractant protein 1, were observed days after the isolation procedure in isolated purified islets. Under culture conditions specially designed to mimic isolation stress, islet proinflammatory responses were even more pronounced and correlated with higher islet cell loss and impaired secretory function. Here we present novel evidence that early interventions aimed at reducing oxidative stress of pancreatic cells and islets through the use of the catalytic antioxidant probe AEOL10150 (manganese [III] 5,10,15,20-tetrakis [1,3,-diethyl-2imidazoyl] manganese-porphyrin pentachloride [TDE-2,5-IP]) effectively reduces NF-kappaB binding to DNA, the release of cytokines and chemokines, and PARP activation in islet cells, resulting in higher survival and better insulin release. These findings support the concept that the isolation process predisposes islets to subsequent damage and functional impairment. Blocking oxidative stress can be beneficial in reducing islet vulnerability and can potentially have a significant impact on transplantation outcome.
Asunto(s)
Antioxidantes/farmacología , Islotes Pancreáticos/citología , Transporte Activo de Núcleo Celular , Adulto , Anciano , Western Blotting , Núcleo Celular/efectos de los fármacos , Núcleo Celular/fisiología , Separación Celular , Humanos , Insulina/farmacología , Interleucina-6/farmacología , Interleucina-8/farmacología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/fisiología , Persona de Mediana Edad , FN-kappa B/metabolismo , Pancreatectomía , Poli(ADP-Ribosa) Polimerasas/metabolismo , Recolección de Tejidos y Órganos/métodosRESUMEN
Troxerutin (TXER) is a derivative of naturally occurring bioflavonoid rutin. It possesses different biological activities in rising clinical world. The biological activity possessed by most of the drugs mainly targets on macromolecules. Hence, in the current study we have examined the interaction mechanism of TXER with calf thymus DNA (CT-DNA) by using various spectroscopic methods, isothermal titration calorimetry (ITC) and molecular docking studies. Further, DNA cleavage study was carried out to find the DNA protection activity of TXER. UV-absorption and emission spectroscopy showed low binding constant values via groove binding. Circular dichroism study indicates that TXER does not modify native B-form of DNA, and it retains the native B-conformation. Furthermore, no effective positive potential peak shift was observed in TXER-DNA complex during electrochemical analysis by which it represents an interaction of TXER with DNA through groove binding. Molecular docking study showed thymine guanine based interaction with docking score -7.09 kcal/mol. This result was compared to experimental ITC value. The DNA cleavage study illustrates that TXER does not cause any DNA damage as well as TXER showed DNA protection against hydroxyl radical induced DNA damage. From this study, we conclude that TXER interacts with DNA by fashion of groove binding.
Asunto(s)
ADN/química , Hidroxietilrutósido/análogos & derivados , Simulación del Acoplamiento Molecular , Análisis Espectral , Animales , Bovinos , ADN/metabolismo , Hidroxietilrutósido/química , Hidroxietilrutósido/metabolismo , Modelos Moleculares , Conformación Molecular , Análisis Espectral/métodosRESUMEN
The studies on the interaction between tRNA (transfer RNA) and small molecules are an area of remarkable recent attention. For this notion a fundamental knowledge of the molecular features involving the interaction of small molecules with tRNA is crucial. Hence, in the present study we have investigated the interaction of TXER (troxerutin), natural bioflavonoid rutin derivative with yeast tRNA by using various spectroscopic techniques and molecular docking studies. The UV absorption and fluorescence emission studies demonstrated external binding of TXER on tRNA with low binding constant values as compared to strong binders. Circular dichroism (CD) spectroscopy study revealed that TXER did not show any significant modification on native conformation of tRNA. Furthermore in electrochemical study, the complex of TXER-tRNA did not expose any noticeable positive potential peak shift which indicated an interaction of TXER with tRNA by electrostatic or external binding mode. The docking study showed that the hydrogen and hydrophobic interactions were involved in binding of TXER-tRNA with docking score -7.0 kcal/mol. These findings led us to confirm the interaction of TXER on tRNA through external binding with low binding affinity, indicating its potential bioapplication in the future.
Asunto(s)
Hidroxietilrutósido/análogos & derivados , Simulación del Acoplamiento Molecular , ARN de Transferencia/química , Sitios de Unión , Dicroismo Circular , Técnicas Electroquímicas , Interacciones Hidrofóbicas e Hidrofílicas , Hidroxietilrutósido/química , Hidroxietilrutósido/metabolismo , Conformación de Ácido Nucleico , ARN de Transferencia/metabolismo , Espectrometría de Fluorescencia , Electricidad EstáticaRESUMEN
Selenium (Se), a dietary micronutrient, plays a vital role in cancer chemotherapy in many organs including the liver. We have studied the relationship between some minerals, which are essential in normal functioning of cells and anticancer effect of Se in N-nitrosodiethylamine (DEN) induced and phenobarbital (PB) promoted multistage hepatocarcinogenesis. Se (4 ppm through drinking water; as sodium selenite) was given to animals throughout the study, before initiation and during promotion phase of hepatocarcinogenesis, in a defined experimental protocol. Se, sodium, potassium, calcium and iron were measured either in hepatoma, or surrounding liver tissue or whole liver tissue and serum of experimental animals. DEN and PB treatment significantly (P < 0.001) increased potassium, calcium and iron levels in serum, while it decreased (P < 0.001) the Se and sodium levels when compared with control rats. We have also observed significantly increased (P < 0.001) sodium, calcium and iron levels in hepatoma and surrounding liver tissue, whereas, Se, and potassium level was found to be decreased (P < 0.001) when compared with control rats. Supplementation of selenite throughout the study, before initiation and during promotion stage significantly alters the above mineral content. Results showed that the most significant beneficial effect of selenium during hepatocarcinogenesis was exerted potentially in long-term continuous and/or before the initiation phase of carcinogenicity, rather than in the promotion phase. The present and previous results from our laboratory suggest that sub-optimal intake of a single trace mineral can have broad effects on chemotherapy, providing a framework for understanding the multiple beneficial effects of selenium in cancer chemoprevention.
Asunto(s)
Antineoplásicos/farmacología , Dietilnitrosamina/análogos & derivados , Neoplasias Hepáticas Experimentales/prevención & control , Fenobarbital , Selenito de Sodio/farmacología , Animales , Antineoplásicos/sangre , Antineoplásicos/uso terapéutico , Carcinógenos , Dieta , Hierro/análisis , Hígado/química , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/metabolismo , Masculino , Ratas , Ratas Wistar , Selenito de Sodio/sangre , Selenito de Sodio/uso terapéuticoRESUMEN
As part of a substantial effort to curtail the adverse health effects posed by hepatoma, studies have been conducted to elucidate the possible mechanism for the anticarcinogenic action of sodium selenite against N-nitrosodiethylamine induced hepatocarcinogenesis. Sodium selenite administered through drinking water at a dose of 4 ppm before initiation, or during initiation and/or during the promotion period of carcinogenesis exerted an in vivo stabilizing effect on cell membranes in rat hepatoma. This was demonstrated in normal rats and in animals whose biomembranes were rendered fragile by induction of hepatoma with N-nitrosodiethylamine and subsequent treatment with sodium selenite. The obtained results have shown a significant decrease in the activities of Na(+)/K(+)-ATPases, Mg(2+)-ATPases and Ca(2+)-ATPases (P < 0.001) in erythrocyte membrane; hepatoma and surrounding liver tissue and also erythrocyte membrane are more susceptible to lysis in cancer-bearing animals. The selenite administration reversed these adverse changes to near normal in selenite-treated animals. Such stabilization of biomembranes by selenite has a beneficial effect in the treatment of hepatoma and other cancers involving abnormal fragility of cell membrane. Previous evidence from this laboratory with respect to the anticancer potency of selenite against N-nitrosodiethylamine-induced hepatoma together with the present results suggests that potentially effective therapeutic protection can be achieved by pre-supplementation of selenite.
Asunto(s)
Antioxidantes/farmacología , Carcinógenos/toxicidad , Dietilnitrosamina/toxicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/enzimología , Fenobarbital/toxicidad , Selenito de Sodio/farmacología , Adenosina Trifosfatasas/sangre , Animales , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/enzimología , Masculino , Fragilidad Osmótica/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
The anticarcinogenic/antioxidant potential of sodium selenite (Se), a micronutrient, was evaluated on liver tumourigenesis induced by N-nitrosodiethylamine (DEN) and promoted by phenobarbital (PB; 0.05% in diet). Male, albino rats of the Wistar strain were exposed intravenously to a single dose of DEN (200 mg x kg(-1) body weight). Se (4 ppm in drinking water) was supplemented before initiation, or during initiation and/or during the promotion period of carcinogenesis. At the end of 16 weeks (after DEN administration) nodular incidence, the total number of nodules and non-enzymic antioxidants such as vitamin E, vitamin C, total thiol, protein thiol and non-protein thiol contents were measured in hepatoma, surrounding tissue and kidney tissue of control and experimental groups. In hepatoma-bearing animals the above biochemical changes were decreased when compared with normal control animals. On Se treatment throughout the study, (20 weeks) the above biochemical changes reverted to normal levels. Pre- and post-treatment with Se also shows a tendency to reverse the above changes. The results indicate that prior application of Se significantly reverses the adverse changes produced during the tumourigenesis. Furthermore, prior applications of Se significantly reduced the cumulative number of tumours per tumour-bearing animals. The present study reveals the antitumour potential of Se against DEN-induced liver carcinogenesis.
Asunto(s)
Anticarcinógenos/uso terapéutico , Antioxidantes/uso terapéutico , Neoplasias Hepáticas Experimentales/prevención & control , Selenito de Sodio/uso terapéutico , Animales , Ácido Ascórbico/análisis , Enfermedad Hepática Inducida por Sustancias y Drogas , Cocarcinogénesis , Dietilnitrosamina/toxicidad , Evaluación Preclínica de Medicamentos , Hiperplasia , Hígado/química , Hígado/efectos de los fármacos , Hepatopatías/prevención & control , Neoplasias Hepáticas Experimentales/inducido químicamente , Masculino , Fenobarbital/toxicidad , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/prevención & control , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/análisis , Vitamina E/análisisRESUMEN
Crocetin (5-20 microg/ml), quercetin (10-40 microg/ml), and cisplatin (60-180 microg/ml) used as a positive control drug, were tested against human rhabdomyosarcoma (RD) cells and African green monkey kidney (Vero) cells. The cell viability, morphological changes, and lactate dehydrogenase activity were assessed. RD cell growth was found to be inhibited dose dependently by the three tested compounds. Morphological observation by phase contrast microscopy revealed that both crocetin and quercetin caused intense damage only on the malignant (RD) cells, whereas mild toxic effect was seen with cisplatin also on normal (Vero) cells.
Asunto(s)
Anticarcinógenos/uso terapéutico , Carotenoides/farmacología , Quercetina/farmacología , Rabdomiosarcoma/tratamiento farmacológico , Animales , Anticarcinógenos/farmacología , Chlorocebus aethiops , Cisplatino/farmacología , Relación Dosis-Respuesta a Droga , Humanos , L-Lactato Deshidrogenasa/efectos de los fármacos , Células Tumorales Cultivadas/efectos de los fármacos , Vitamina A/análogos & derivadosRESUMEN
The bio reduction of chloro auric acid (HAuCl(4)) and silver nitrate (AgNO(3)) is achieved extracellularly by using the aqueous extract of Solanum torvum (S. torvum) fruit. The nanoparticle formation was screened by UV-visible spectroscopy through color conversion due to surface plasma resonance bands at 560 nm and 430 nm for gold and silver nanoparticles respectively. The spherical shapes with smooth surface of gold and silver nanoparticles were analyzed through scanning electron microscope and its presence was confirmed by energy dispersive X-ray spectroscopy (SEM/EDX). The functional groups in the gold and silver salts and the bio interactive functional groups present in the S. torvum extract were characterized by employing Fourier transform infra-red spectroscopy (FTIR). The biomedical properties of gold and silver nanoparticles were premeditated as free radical scavenging activity and antibacterial static agents. Gold and silver nanoparticles serve as strong hydroxyl, superoxide, nitric oxide and DPPH radical scavengers in contrast to their corresponding metal oxides. The radical quenching properties of gold and silver nanoparticles were found to correlate with in vitro DNA protective effect. The silver nanoparticles show strong zone of inhibition against Escherichia coli, Pseudomonas and Bacillus whereas, gold nanoparticles exhibit fair zone of inhibition. To our knowledge this is the first report that S. torvum extract can reduce metal acids to nano materials.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Depuradores de Radicales Libres/química , Oro/química , Nanopartículas del Metal/química , Plata/química , Bacillus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pseudomonas/efectos de los fármacosRESUMEN
Hyaluronidase inhibitors have immense applications in pathophysiological conditions associated with hyaluronan-hyaluronidase system. The present study demonstrates the inhibitory efficacy of clinically accepted antioxidant N-acetyl cysteine (NAC) against hyaluronidase of serum, testis, and snake and bee venoms. The experimental and molecular dynamic simulation data suggest the non-competitive inhibition and involvement of thiol groups of both NAC and glutathione in exertion of inhibition. The bioavailability, less-toxic and antioxidant nature of NAC and glutathione could become valuable in the management of pathologies triggered by extracellular matrix degradation and to increase the endurance of hyaluronan based biomaterials/supplements, which are highly exciting aspects.
Asunto(s)
Acetilcisteína/farmacología , Glutatión/farmacología , Hialuronoglucosaminidasa/antagonistas & inhibidores , Acetilcisteína/química , Acetilcisteína/metabolismo , Animales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Glutatión/química , Glutatión/metabolismo , Hialuronoglucosaminidasa/química , Hialuronoglucosaminidasa/metabolismo , Cinética , Conformación Molecular , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Unión ProteicaRESUMEN
Profound research has been done on the medicinal value of Brassica nigra (BN) seeds, and the leaves of the plant have been investigated in this study. The methanol extracts of the leaves were subjected to several in vitro studies. The antioxidant activity of methanol extract was demonstrated with a wide range of concentration, 10-500 µg mL(-1), and the antioxidant activity increased with the increase in concentration. Total phenol content was found to be 171.73 ± 5.043 gallic acid equivalents and the total flavonoid content 7.45 ± 0.0945 quercetin equivalents. Further quantification and identification of the compounds were done by HPTLC and GC-MS analyses. The predominant phenolic compounds determined by HPTLC were gallic acid, followed by quercetin, ferulic acid, caffeic acid and rutin. The free radical quenching property of BN leaf extract suggests the presence of bioactive natural compounds.
Asunto(s)
Antioxidantes/farmacología , Planta de la Mostaza/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polifenoles/análisis , Antioxidantes/química , Ácidos Cafeicos/análisis , Ácidos Cumáricos/análisis , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/química , Ácido Gálico/análisis , Cromatografía de Gases y Espectrometría de Masas , Concentración 50 Inhibidora , Extractos Vegetales/análisis , Hojas de la Planta/química , Quercetina/análisis , Rutina/análisisRESUMEN
UNLABELLED: Solanum torvum fruit widely used in traditional medicine of India and also in food preparation. Three different extracts such as water (WE), methanol (ME), and ethanol (EE) were used to evaluate their antioxidant and radical scavenging activity by different methods. All the assays results were compared with well-known standard antioxidants. The IC(50) values of assays were determined. The total phenolic and flavonoids content were found to be maximum in water and ethanol extracts, respectively. The electron quenching ability of fruit extract was assayed by DPPH and reducing power assays succeeding order were ME > EE > WE, respectively. Inhibition of membrane damage, was assayed interns of oxidative hemolysis and lipid peroxidation assays, among all WE extract shows 58.00% and 68.55 5% percentage of inhibition with 0.9 and 0.8 correlations (r(2)), respectively. Antioxidant and radical quenching efficiency were assayed by ß-carotene bleaching and hydroxyl radical scavenging method and results were compared with vitamin C and catechin. The in vitro free radical quenching and antioxidant results were well correlated with in vitro DNA protection assay. As analyzed by HPTLC gallic acid content is high in WE (1394 ± 25.0) and ME (598 ± 54.0) whereas ferulic acid is high in EE (32 ± 5.94) µg/g, respectively. This study indicate that S. torvum fruit is an excellent source of natural antioxidant and could be an effective nutritional food supplement, which interns will have therapeutic applications. PRACTICAL APPLICATION: In siddha medicine on the traditional systems of India the, ripened fruits are used in the preparation of tonic named as a "sundaivattaral choornam" is used to improve the health and prevent several diseases. This study has given an experimental evidence that S. torvum fruit is an excellent source of natural antioxidants.