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1.
Sci Rep ; 12(1): 2195, 2022 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-35140281

RESUMEN

The present study aimed to assess the toxic effects of pendimethalin herbicide and protective role of curcumin using the Allium test on cytological, biochemical and physiological parameters. The effective concentration (EC50) of pendimethalin was determined at 12 mg/L by the root growth inhibition test as the concentration reducing the root length by 50%. The roots of Allium cepa L. was treated with tap water (group I), 5 mg/L curcumin (group II), 10 mg/L curcumin (group III), 12 mg/L pendimethalin (group IV), 12 mg/L pendimethalin + 5 mg/L curcumin (group V) and 12 mg/L pendimethalin + 10 mg/L curcumin (group VI). The cytological (mitotic index, chromosomal abnormalities and DNA damage), physiological (rooting percentage, root length, growth rate and weight gain) and oxidative stress (malondialdehyde level, superoxide dismutase level, catalase level and glutathione reductase level) indicators were determined after 96 h of treatment. The results revealed that pendimethalin treatment reduced rooting percentage, root length, growth rate and weight gain whereas induced chromosomal abnormalities and DNA damage in roots of A. cepa L. Further, pendimethalin exposure elevated malondialdehyde level followed by antioxidant enzymes. The activities of superoxide dismutase and catalase were up-regulated and glutathione reductase was down-regulated. The molecular docking supported the antioxidant enzymes activities result. However, a dose-dependent reduction of pendimethalin toxicity was observed when curcumin was supplied with pendimethalin. The maximum recovery of cytological, physiological and oxidative stress parameters was recorded at 10 mg/L concentration of curcumin. The correlation studies also revealed positive relation of curcumin with rooting percentage, root length, weight gain, mitotic activity and glutathione reductase enzyme level while an inverse correlation was observed with chromosomal abnormalities, DNA damage, superoxide dismutase and catalase enzyme activities, and lipid peroxidation indicating its protective effect.


Asunto(s)
Compuestos de Anilina/toxicidad , Curcumina/farmacología , Herbicidas/toxicidad , Cebollas/genética , Raíces de Plantas/genética , Sustancias Protectoras/farmacología , Aberraciones Cromosómicas/efectos de los fármacos , Correlación de Datos , Daño del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Peroxidación de Lípido/efectos de los fármacos , Simulación del Acoplamiento Molecular , Cebollas/efectos de los fármacos , Cebollas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo
2.
Am J Physiol Regul Integr Comp Physiol ; 316(1): R76-R86, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30462525

RESUMEN

During aerobic exercise (>65% of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate potential of rat gastrocnemius muscle during contraction. Twitch contractions were induced in vivo over a broad range of intensities to sample submaximal and maximal aerobic workloads. Muscle phosphorus metabolites were measured in vivo before and after DCA treatment by phosphorus nuclear magnetic resonance spectroscopy. At rest, DCA increased PDH activation compared with control (90 ± 12% vs. 23 ± 3%, P < 0.05), with parallel decreases in inorganic phosphate (Pi) of 17% (1.4 ± 0.2 vs. 1.7 ± 0.1 mM, P < 0.05) and an increase in the free energy of ATP hydrolysis (ΔGATP) (-66.2 ± 0.3 vs. -65.6 ± 0.2 kJ/mol, P < 0.05). During stimulation DCA increased steady-state phosphocreatine (PCr) and the magnitude of ΔGATP, with concomitant reduction in Pi and ADP concentrations. These effects were not due to kinetic alterations in PCr hydrolysis, resynthesis, or glycolytic ATP production and altered the flow-force relationship between mitochondrial ATP synthesis rate and ΔGATP. DCA had no significant effect at 1.0- to 2.0-Hz stimulation because physiological mechanisms at these high stimulation levels cause maximal activation of PDH. These data support a role of PDH activation in the regulation of the energetic steady state by altering the phosphate potential (ΔGATP) at rest and during contraction.


Asunto(s)
Metabolismo Energético/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/enzimología , Consumo de Oxígeno/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Masculino , Músculo Esquelético/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Consumo de Oxígeno/fisiología , Complejo Piruvato Deshidrogenasa/metabolismo , Complejo Piruvato Deshidrogenasa/farmacología , Ratas Wistar
3.
Stress ; 20(6): 562-572, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28911262

RESUMEN

High ambient temperature adversely influences poultry production. In the present study, gamma amino butyric acid (GABA) supplementation was used to alleviate the adverse changes due to heat stress (HS) in a broiler chicken strain (Ross 308). At 21 days of age, the birds were divided into four groups of 13. Two groups were housed under normal room temperature, one group was given orally 0.2 ml 0.9% physiological saline (CN) daily, the other group received 0.2 ml of 0.5% GABA solution orally (GN). A third group was exposed to environmental HS (33 ± 1 °C lasting for 2 weeks) + physiological saline (CH) and a fourth group was exposed to HS + GABA supplementation (GH). GABA supplementation during HS significantly reduced the birds' increased body temperature (p <.0001) and increased their body weight gain (p <.0001). This effect was associated with increases in the heat stress-induced reductions in jejunal villus length, crypt depth and mucous membrane thickness, and decreases in the vascular changes occurred due to HS. Additionally, GABA supplementation significantly modulated HS-induced changes in glucose facilitated transporter 2 (GLUT2), peptide transporter 1 (PEPT1) and heat shock protein 70 (HSP70) mRNA expression in the jejunal mucosa (p < .0001). GABA supplementation also significantly elevated the triiodothyronine (T3) hormone level and hemoglobin levels and decreased the heterophil-lymphocyte ratio (H/L ratio) (p <.0001). Furthermore, it induced higher hepatic glutathione peroxidase enzyme (GSH-Px) activities and decreased the malondialdehyde dehydrogenase (MDA) content. These results indicate that GABA supplementation during HS may be used to alleviate HS-related changes in broiler chickens.


Asunto(s)
GABAérgicos/farmacología , Transportador de Glucosa de Tipo 2/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/efectos de los fármacos , Respuesta al Choque Térmico/efectos de los fármacos , Calor/efectos adversos , Mucosa Intestinal/efectos de los fármacos , Yeyuno/efectos de los fármacos , Transportador de Péptidos 1/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacología , Animales , Pollos , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 2/metabolismo , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Trastornos de Estrés por Calor , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Yeyuno/metabolismo , Yeyuno/patología , Hígado/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Transportador de Péptidos 1/genética , Transportador de Péptidos 1/metabolismo , ARN Mensajero/metabolismo , Estrés Fisiológico/efectos de los fármacos
4.
BMC Complement Altern Med ; 17(1): 139, 2017 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-28259154

RESUMEN

BACKGROUND: Coreopsis tinctoria is a traditional remedy for the management of various diseases including hepatitis. The hepatoprotective role of the plant is not scientifically explored till now. This study was designed to investigate the hepatoprotective potentials of the ethanol extract from C. tinctoria (CTEtOH) using an animal model of carbon tetrachloride (CCl4)-induced acute liver injury. METHODS: CTEtOH (0.5 and 1.0 g/kg) and silymarin (200 mg/kg) were administered to the experimental mice for 7 days followed by 0.2% CCl4 (10 mL/kg of body weight (bw), ip), then all mice were sacrificed after 24 h. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Histological analysis of liver was performed. The tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), nitric oxide (NO), malondialdehyde (MDA), and antioxidant enzymatic activities were also measured.. RESULTS: The results revealed that the serum ALT and AST levels significantly decreased after treatment with CTEtOH. Moreover, histological analyses indicated that CTEtOH (0.5 and 1.0 g/kg) and silymarin reduced the extent of CCl4-induced liver lesions. CTEtOH (0.5 and 1.0 g/kg) reduced the levels of malondialdehyde, nitric oxide, and proinflammatory cytokines (TNF-α and IL-1ß). Furthermore, CTEtOH (1.0 g/kg) reduced the level of IL-6. The activities of antioxidant enzymes, namely superoxide dismutase and glutathione reductase, significantly increased after treatment with CTEtOH (0.5 and 1.0 g/kg) and that of glutathione peroxidase increased after treatment with 1.0 g/kg of CTEtOH. CONCLUSIONS: These results demonstrate the hepatoprotective effect of CTEtOH against CCl4-induced acute liver injury in mice, and the underlying hepatoprotective mechanisms are associated with antioxidant and antiproinflammatory activities.


Asunto(s)
Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Coreopsis/química , Flores/química , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Animales , Citocinas , Hígado/patología , Ratones , Ratones Endogámicos ICR , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Extractos Vegetales/química , Sustancias Protectoras/química
5.
J Dermatol Sci ; 80(3): 203-11, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26475433

RESUMEN

BACKGROUND: The mouse pink-eyed dilution (oculocutaneous albinism II; p/Oca2(p)) locus is known to control tyrosinase activity, melanin content, and melanosome development in melanocytes. Pink-eyed dilution castaneus (p(cas)/Oca2(p-cas)) is a novel mutant allele on mouse chromosome 7 that arose spontaneously in Indonesian wild mice, Mus musculus castaneus. Mice homozygous for Oca2(p-cas) usually exhibit pink eyes and beige-colored coat on nonagouti C57BL/6 (B6) background. Recently, a novel spontaneous mutation occurred in the progeny between this mutant and B6 mice. The eyes of this novel mutant progressively become black from pink and the coat becomes dark gray from beige with aging. OBJECTIVE: The aim of this study is to clarify whatever differences exist in melanocyte proliferation and differentiation between the ordinary (pink-eyed) and novel (black-eyed) mutant using serum-free primary culture system. METHODS: The characteristics of melanocyte proliferation and differentiation were investigated by serum-free primary culture system using melanocyte-proliferation medium (MDMD). RESULTS: The proliferation of melanoblasts in MDMD did not differ between the two mice. However, when the epidermal cell suspensions were cultured with MDMD supplemented with l-tyrosine (Tyr), the differentiation of black-eyed melanocytes was greatly induced in a concentration-dependent manner compared with pink-eyed melanocytes. Immunocytochemistry demonstrated that the expression of tyrosinase and tyrosinase-related protein-1 (Tyrp1) was greatly induced or stimulated both in pink-eyed and black-eyed melanocytes, whereas the expression of microphthalmia-associated transcription factor (Mitf) was stimulated only in black-eyed melanocytes. CONCLUSION: These results suggest that the age-related coat darkening in black-eyed mutant may be caused by the increased ability of melanocyte differentiation dependent on l-Tyr through the upregulation of tyrosinase, Tyrp1, and Mitf. This mutant mouse may be useful for animal model to clarify the mechanisms of age-related pigmentation in human skin, such as melasma and solar lentigines.


Asunto(s)
Envejecimiento , Albinismo Oculocutáneo/genética , Diferenciación Celular/efectos de los fármacos , Melanocitos/efectos de los fármacos , ARN Mensajero/metabolismo , Tirosina/farmacología , Animales , Proliferación Celular , Oxidorreductasas Intramoleculares/efectos de los fármacos , Oxidorreductasas Intramoleculares/metabolismo , Glicoproteínas de Membrana/efectos de los fármacos , Glicoproteínas de Membrana/metabolismo , Ratones , Factor de Transcripción Asociado a Microftalmía/efectos de los fármacos , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismo , Monofenol Monooxigenasa/efectos de los fármacos , Monofenol Monooxigenasa/metabolismo , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Cultivo Primario de Células , Regulación hacia Arriba/efectos de los fármacos
6.
J Complement Integr Med ; 11(1): 35-41, 2014 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-24413220

RESUMEN

Liver is the major site for several xenobiotics metabolism, and formation of toxic metabolites that may be hepatotoxic, therefore the burden of metabolism and exposure to dangerous chemicals make liver vulnerable to a variety of disorders. Our work aimed to investigate the effects of some antioxidants such as lipoic acid (LA), S-adenosyl methionine (SAM) and vitamin E in a trail to investigate the possibility of using these substances to relieve and protect liver from exposure to monocrotaline (MCT). Twenty-five mature adult rats were classified into five groups (five rats in each group), control group, MCT-induced hepatic damage, LA+MCT, SAM+MCT and vitamin E+MCT group. Homogenates of liver samples were used for measuring the oxidative biomarkers and hepatic antioxidant status. The results showed that administration of vitamin E, SAM and LA caused a significant increase in liver glutathione contents, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and a significant decrease in hepatic catalase and superoxide dismutase. We could conclude that administration of natural LA, SAM and vitamin E before and after MCT injection modulate the hepatic oxidative stresses induced by MCT in various extents.


Asunto(s)
Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Monocrotalina/toxicidad , Oxidantes/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Ratas , S-Adenosilmetionina/farmacología , Ácido Tióctico/farmacología , Vitamina E/farmacología
7.
BMC Complement Altern Med ; 13: 361, 2013 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-24341420

RESUMEN

BACKGROUND: Grape skin, a rich source of phytochemicals, has been reported to possess remarkable anti-obesity activity. Fatty acid synthase (FAS) is a key enzyme catalyzing the synthesis of fatty acid de novo, and has been considered as an anti-obesity target. To elucidate the anti-obesity mechanism of grape skin, we investigated the effects of grape skin extract (GSE) and resveratrol, one of the phytochemicals in GSE, on FAS and FAS over-expressed 3 T3-L1 preadipocyte. METHODS: Purified FAS was obtained from chicken liver. Dried grape skin was extracted by 50% ethanol and partitioned by ethyl acetate. Inhibitory effects of GSE and resveratrol on FAS including fast-binding inhibition, time-dependent inhibition, and enzyme kinetics were determined. Inhibitory effects of GSE and resveratrol on 3T3-L1 preadipocyte were also measured. RESULTS: GSE inhibited the overall reaction and ß-ketoacyl reductase (KR) reaction of FAS with IC50 values of 4.61 µg/ml and 20.3 µg/ml. For inhibition by resveratrol, the relevant IC50 values were 11.1 µg/ml and 21.9 µg/ml, respectively. And both GSE and resveratrol showed time-dependent inhibition for FAS, with the kobs values of 0.028 min-1, and 0.040 min-1 respectively. They inhibited the overall reaction of FAS competitively with acetyl-CoA, noncompetitively with malonyl-CoA and in a mixed manner with NADPH. Moreover, the inhibition on KR domain by resveratrol was time-dependent with kobs value of 0.106 min-1. In 3 T3-L1 preadipocytes, resveratrol reduced lipid accumulation remarkably. CONCLUSIONS: GSE and resveratrol are potent FAS inhibitors and they bound reversibly to the KR domain of FAS to inhibit the reduction of the saturated acyl groups in fatty acid synthesis. Based on the valid data and deliberate analysis, we proposed that GSE and resveratrol have great medical potential and officinal value in treating obesity and related diseases.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Ácido Graso Sintasas/antagonistas & inhibidores , Ácido Graso Sintasas/efectos de los fármacos , Extractos Vegetales/farmacología , Vitis/química , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Inhibidores Enzimáticos/química , Ácido Graso Sintasas/metabolismo , Lípidos/análisis , Lipogénesis/efectos de los fármacos , Ratones , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Extractos Vegetales/química , Resveratrol , Estilbenos/química , Estilbenos/farmacología
8.
Comput Biol Chem ; 47: 121-5, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24055764

RESUMEN

Tuberculosis continues to plague the world with the World Health Organization estimating that about one third of the world's population is infected. Due to the emergence of MDR and XDR strains of TB, the need for novel therapeutics has become increasing urgent. Herein we report the results of a virtual screen of 4.1 million compounds against a promising drug target, DrpE1. The virtual compounds were obtained from the Zinc docking site and screened using the molecular docking program, AutoDock Vina. The computational hits have led to the identification of several promising lead compounds.


Asunto(s)
Proteínas Bacterianas/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Ensayos Analíticos de Alto Rendimiento , Mycobacterium tuberculosis/enzimología , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas de Alcohol , Mycobacterium tuberculosis/citología , Mycobacterium tuberculosis/efectos de los fármacos
9.
Oral Dis ; 17(7): 677-84, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21729219

RESUMEN

OBJECTIVE: This study aims to investigate the effects of genistein on contractile properties of genioglossus under chronic intermittent hypoxia (CIH) conditions and its relationship with oxidative stress, antioxidant enzyme, and ERK1/2 signaling pathway. MATERIALS AND METHODS: Fifty female Sprague-Dawley rats were randomly divided into five groups 1 week after ovariectomy: the normal control group, the CIH group, the CIH with low-dose, medium-dose, and high-dose genistein groups. Rats in the latter four groups were exposed to CIH for 5 weeks. Twitch tension, tetanic tension, and fatigue resistance of genioglossus were investigated. Malondialdehyde (MDA) and mitochondrial reactive oxygen species (ROS), enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and ERK1/2 were detected. RESULTS: Muscle fatigue resistance and enzymatic activity of GPx, CAT, and SOD were reduced after CIH exposure and improved by different doses of genistein at different degrees. CIH increased the level of ROS and MDA, and they were returned to normal by genistein. The expression of phospho-ERK1/2 is opposite to the changes in muscle fatigue resistance. CONCLUSION: Chronic intermittent hypoxia decreases fatigue resistance of genioglossus, and genistein treatment reverses the fatigability of genioglossus by down-regulation of oxidative stress level and up-regulation of antioxidant enzymatic activity probably through ERK1/2 signaling pathway.


Asunto(s)
Antioxidantes/farmacología , Músculos Faciales/efectos de los fármacos , Genisteína/farmacología , Hipoxia/fisiopatología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fatiga Muscular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Animales , Catalasa/análisis , Catalasa/efectos de los fármacos , Regulación hacia Abajo , Femenino , Glutatión Peroxidasa/análisis , Glutatión Peroxidasa/efectos de los fármacos , Contracción Isométrica/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/análisis , Mitocondrias Musculares/efectos de los fármacos , Tono Muscular/efectos de los fármacos , Ovariectomía , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/análisis , Superóxido Dismutasa/análisis , Superóxido Dismutasa/efectos de los fármacos , Factores de Tiempo , Regulación hacia Arriba
10.
Int Endod J ; 44(2): 154-61, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21083578

RESUMEN

AIM: To evaluate the cytotoxicity of two forms of the novel root-end filling materials, polymer nanocomposite (PNC) resins [C-18 Amine montmorillonate (MMT) and VODAC MMT] both containing Chlorhexidine Diacetate Salt Hydrate 2%, and to compare it to that of two widely accepted commercially available materials, ProRoot® MTA and Geristore®. METHODOLOGY: Elutes of experimental materials extracted after 24 h, 1, 2 and 3 weeks were interacted with the mouse fibroblasts L-929 using a colorimetric cell viability assay (MTS) based on mitochondrial dehydrogenases activity. Using 100% and 50% concentrations of the extracted elutes of the experimental materials the effect of different concentrations of elutes on the cells was analysed. In the positive control group Hygrogold® was added to the cell culture to arrest cells bioactivity. In the negative control group, fresh Dulbecco's Eagle's minimum essential medium supplemented with 10% foetal bovine serum was used to enhance cell bioactivity. Differences in mean bioactivity values were assessed using a t-test and one-way anova (P<0.05). RESULTS: No significant difference was found in cytotoxicity between ProRoot® MTA, Geristore® and PNC resin C-18 Amine MMT on 24 h, 1, 2 and 3 weeks samples. Sample elutes of PNC resin VODAC MMT, however, revealed cytotoxic activity during most of these experiments. CONCLUSION: Cytotoxicity of the elutes of PNC resin C-18 Amine MMT was not significantly different from that of ProRoot® and Geristore®. PNC resin VODAC MMT, revealed significantly more cytotoxicity compared to the other tested materials.


Asunto(s)
Resinas Compuestas/toxicidad , Cementos Dentales/toxicidad , Fibroblastos/efectos de los fármacos , Nanocompuestos/toxicidad , Materiales de Obturación del Conducto Radicular/toxicidad , Compuestos de Aluminio/química , Compuestos de Aluminio/toxicidad , Análisis de Varianza , Animales , Bentonita/química , Bentonita/toxicidad , Compuestos de Calcio/química , Compuestos de Calcio/toxicidad , Supervivencia Celular , Células Cultivadas , Clorhexidina/química , Resinas Compuestas/química , Cementos Dentales/química , Combinación de Medicamentos , Fibroblastos/enzimología , Cementos de Ionómero Vítreo/química , Cementos de Ionómero Vítreo/toxicidad , Ratones , Nanocompuestos/química , Óxidos/química , Óxidos/toxicidad , Oxidorreductasas/efectos de los fármacos , Polímeros/química , Polímeros/toxicidad , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/toxicidad , Resinas Sintéticas/química , Resinas Sintéticas/toxicidad , Materiales de Obturación del Conducto Radicular/química , Silicatos/química , Silicatos/toxicidad , Estadísticas no Paramétricas , Factores de Tiempo , Pruebas de Toxicidad Crónica/métodos
11.
Planta Med ; 77(6): 586-97, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20945274

RESUMEN

Trypanosoma brucei is the causative agent of human African trypanosomiasis (sleeping sickness) which is fatal if left untreated. This disease occurs in 36 African countries, south of the Sahara, where 60 million people are at risk of acquiring infection. The current chemotherapy relies on only four drugs, three of which were developed more than 60 years ago. These drugs have many limitations, ranging from oral inabsorption, acute toxicities, short duration of action and the emergence of trypanosomal resistance. Despite decades of use of most of the current trypanocides, little is known about their mode of action. That being said, African trypanosomes continue to be among the most extensively studied parasitic protists to date. Many of their intriguing biological features have been well documented and can be viewed as attractive targets for antitrypanosomal chemotherapy. A considerable number of natural products with diverse molecular structures have revealed antiparasitic potency in the laboratory and represent interesting lead compounds for the development of new and urgently needed antiparasitics. The major validated drug targets in T. brucei are discussed with particular emphasis on those known to be attacked by natural compounds.


Asunto(s)
Productos Biológicos/farmacología , Tripanocidas/uso terapéutico , Trypanosoma brucei brucei/efectos de los fármacos , Tripanosomiasis Africana/tratamiento farmacológico , África/epidemiología , Animales , Productos Biológicos/química , Productos Biológicos/uso terapéutico , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , ADN-Topoisomerasas/efectos de los fármacos , ADN de Cinetoplasto/efectos de los fármacos , Descubrimiento de Drogas/métodos , Evaluación Preclínica de Medicamentos/métodos , Resistencia a Medicamentos , Farnesiltransferasa/efectos de los fármacos , Humanos , Oxidorreductasas/efectos de los fármacos , Proteínas Protozoarias/efectos de los fármacos , Compuestos de Sulfhidrilo/metabolismo , Tripanocidas/química , Tripanocidas/aislamiento & purificación , Trypanosoma brucei brucei/metabolismo , Trypanosoma brucei brucei/patogenicidad , Tripanosomiasis Africana/epidemiología , Tubulina (Proteína)/efectos de los fármacos
12.
Drug Chem Toxicol ; 33(2): 120-30, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20307140

RESUMEN

Oxidative stress is produced under diabetic conditions and is likely involved in the progression of pancreatic damage found in diabetes. This study was undertaken to evaluate the protective effect of Aegle marmelos leaf extract, a medicinal plant, on the tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Ethanol extract of A. marmelos was administered orally for 30 days (150 mg/kg body weight/day) to diabetic rats. Activity of the three primary scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), levels of glutathione, and lipid peroxidation were estimated in plasma and pancreas of diabetic rats and compared to the reference drug, glibenclamide (600 microg/kg body weight/day). A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, lipid peroxides, and a concomitant decrease in the levels of vitamin C and reduced glutathione were observed in diabetic rats. The activities of antioxidant enzymes were altered in diabetic rats. These alterations were reverted back to near normal levels after treatment with A. marmelos and glibenclamide. Histopathological studies also revealed the protective effect of A. marmelos on pancreatic beta-cells. The present study indicates that extract of A. marmelos modulates the activity of enzymic and nonenzymic antioxidants and enhances the defense against reactive oxygen species-generated damage in diabetic rats.


Asunto(s)
Aegle/química , Antioxidantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Células Secretoras de Insulina/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Administración Oral , Animales , Glucemia/análisis , Glucemia/efectos de los fármacos , Ceruloplasmina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glutatión/metabolismo , Gliburida/farmacología , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/farmacología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/fisiología , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Hojas de la Planta/química , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
13.
Food Chem Toxicol ; 48(4): 1019-25, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20079793

RESUMEN

Anti-oxidative potential of Rhodiola imbricata root aqueous extract was examined in rats, administered orally at a dose of 100 mg/kg both in single and multiple doses, 30 min prior to cold (5 degrees C)-hypoxia (428 mmHg)-restraint (C-H-R) exposure. Lipid per-oxidation, anti-oxidant parameters and lactate dehydrogenase (LDH), were studied in blood, liver and muscle of rats on attaining T(rec)23 degrees C during C-H-R exposure and after recovery (T(rec)37 degrees C) from C-H-R induced hypothermia. The results of untreated control rats on attaining T(rec)23 degrees C showed a significant increase in blood, liver and muscle malondialdehyde (MDA) and LDH levels. Hepatic catalase (CAT) and muscle glutathione S-transferase (GST) also increased significantly. Administration of single dose of Rhodiola imbricata root aqueous extract significantly restricted rise in blood MDA, increased blood reduced glutathione (GSH) and superoxide dismutase (SOD) activity with restricted rise in blood, liver and muscle LDH; improved liver and muscle SOD on attaining T(rec)23 degrees C and T(rec)37 degrees C; liver CAT on attaining T(rec)23 degrees C and liver GST during recovery. Multiple doses treatment of the extract further increased blood, liver and muscle GSH and GST levels; restricted increase in LDH on attaining T(rec)23 degrees C and recovery; increased CAT during recovery. Results suggested the anti-oxidant potential of Rhodiola root extract during C-H-R exposure and post-stress recovery and it also maintained cell membrane permeability.


Asunto(s)
Antioxidantes/farmacología , Hipotermia/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Extractos Vegetales/farmacología , Rhodiola/química , Estrés Psicológico/tratamiento farmacológico , Administración Oral , Animales , Cromatografía Líquida de Alta Presión , Hipotermia/complicaciones , Hipotermia/fisiopatología , Hipoxia/complicaciones , Hipoxia/fisiopatología , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Raíces de Plantas/química , Ratas , Recuperación de la Función , Restricción Física , Estrés Psicológico/etiología , Agua/química
14.
Food Chem Toxicol ; 48(4): 1032-9, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20096321

RESUMEN

Environmental arsenic (As) is a potent human carcinogen and groundwater As contamination is a major health concern in West Bengal, India. Oxidative stress has been one of the prime factors in As-induced carcinogenicity. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance cause a severe imbalance of the cellular antioxidant defence mechanism. Tea, a popular beverage has excellent chemopreventive and antioxidant properties. In this study it was investigated whether these flavonoids could ameliorate the arsenite (As III) induced oxidative stress in Swiss albino mice. Bio-monitoring with comet assay elicited that the increase in genotoxicity caused by As III was counteracted by both black tea and green tea. Elevated levels of lipid peroxides and protein carbonyl by As III were effectively reduced with green as well as black tea. They also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the tea polyphenols by virtue of their antioxidant potential may be used as an effective agent to reduce the As III induced oxidative stress in Swiss albino mice.


Asunto(s)
Antioxidantes/farmacología , Intoxicación por Arsénico/prevención & control , Arsénico/toxicidad , Carcinógenos Ambientales/toxicidad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Té/química , Animales , Antioxidantes/química , Intoxicación por Arsénico/metabolismo , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Extractos Vegetales/química , Carbonilación Proteica/efectos de los fármacos
15.
Food Chem Toxicol ; 48(4): 1005-12, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20109512

RESUMEN

The present study investigated the modulatory role of phenolic extract of soybean (PESB) in a rat model of nephrotoxic acute renal failure induced by cisplatin. Cisplatin (2 mg/kg/day) was administered to the rats for 5 days and the animals were pretreated with PESB (250-1000 mg/kg). Blood urea nitrogen reduced by 49.8% and 59.0%, serum creatinine by 34.7% and 62.1% and urinary N-acetyl-beta-D-glucosaminidase also decreased by 37.7% and 49.2% following treatment with 250- and 500-mg/kg doses of the extract respectively in the cisplatin-treated rats. The extract also significantly increased renal myeloperoxidase activity by 26.8% and 40.6% at these doses. PESB also decreased renal xanthine oxidase activity and serum nitrate/nitrite in the cisplatin-treated rats. In addition, PESB significantly attenuated the marked renal oxidative damage that accompanied cisplatin treatment. The extract improved liver histology and significantly increased the activities of the antioxidant enzymes measured [superoxide dismutase, catalase, glutathione-S-transferase], prevented glutathione depletion and decreased malondialdehyde level following cisplatin treatment. Furthermore, cisplatin-induced decrease in the activities of glucose-6-phosphatase and 5'-nucleotidase in these rats was attenuated only at 250 mg/kg dose of the extract. We concluded therefore that PESB via antioxidant and possibly anti-inflammatory actions offered protective benefit against cisplatin-mediated acute toxic injury to the kidney.


Asunto(s)
Lesión Renal Aguda/prevención & control , Antineoplásicos/toxicidad , Antioxidantes/farmacología , Cisplatino/toxicidad , Glycine max/química , Extractos Vegetales/farmacología , 5'-Nucleotidasa/efectos de los fármacos , 5'-Nucleotidasa/metabolismo , Acetilglucosaminidasa/orina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Modelos Animales de Enfermedad , Glucosa-6-Fosfatasa/efectos de los fármacos , Glucosa-6-Fosfatasa/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/patología , Pruebas de Función Renal , Malondialdehído/metabolismo , Nitratos/sangre , Nitritos/sangre , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Peroxidasa/efectos de los fármacos , Peroxidasa/metabolismo , Fenol/química , Ratas , Ratas Wistar
16.
Food Chem Toxicol ; 47(10): 2499-506, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19602430

RESUMEN

The effects of cocoa feeding against N-nitrosodiethylamine (DEN)-induced liver injury were studied in rats. Animals were divided into five groups. Groups 1 and 2 were fed with standard and cocoa-diet, respectively. Groups 3 and 4 were injected with DEN at 2 and 4 weeks, and fed with standard and cocoa-diet, respectively. Group 5 was treated with DEN, received the standard diet for 4 weeks and then it was replaced by the cocoa-diet. DEN-induced hepatic damage caused a significant increase in damage markers, as well as a decrease in the hepatic glutathione, diminished levels of p-ERK and enhanced protein carbonyl content, caspase-3 activity and values of p-AKT and p-JNK. The cocoa-rich diet prevented the reduction of hepatic glutathione concentration and catalase and GPx activities in DEN-injected rats, as well as diminished protein carbonyl content, caspase-3 activity, p-AKT and p-JNK levels, and increased GST activity. However, cocoa administration did not abrogate the DEN-induced body weight loss and the increased levels of hepatic-specific enzymes and LDH. These results suggested that cocoa-rich diet attenuates the DEN-induced liver injury.


Asunto(s)
Antioxidantes/farmacología , Cacao/química , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Dietilnitrosamina/toxicidad , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Peso Corporal/efectos de los fármacos , Caspasa 3/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Antagonismo de Drogas , Ingestión de Alimentos/efectos de los fármacos , Glutatión/metabolismo , Hígado/enzimología , Hígado/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Polvos , Ratas , Ratas Sprague-Dawley
17.
J Environ Sci Health B ; 44(5): 461-71, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20183051

RESUMEN

A pot trial was carried out to investigate the adverse effects of tetracycline (TC) on soil microbial communities, microbial activities, and the growth of ryegrass (Lolium perenne L). The results showed that the presence of TC significantly disturbed the structure of microbial communities and inhibited soil microbial activities in terms of urease, acid phosphatase and dehydrogenase (p < 0.05). Plant biomass was adversely influenced by TC, especially the roots with a reduction of 40% when compared with the control. Furthermore, TC decreased the assimilation of phosphorus by the plant although the concentration of phosphorus was increased by 20% due to decreased plant biomass. TC seemed to increase the concentration of dissolved organic carbon (by 20%) in soil. The findings implied that the agricultural use of animal manure or fishpond sediment containing considerable amounts of antibiotics may give rise to ecological risks.


Asunto(s)
Residuos de Medicamentos/toxicidad , Activación Enzimática/efectos de los fármacos , Lolium/crecimiento & desarrollo , Microbiología del Suelo , Tetraciclina/toxicidad , Animales , Bacterias/efectos de los fármacos , Bacterias/enzimología , Biomasa , Carbono/metabolismo , Residuos de Medicamentos/metabolismo , Lolium/efectos de los fármacos , Estiércol , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Monoéster Fosfórico Hidrolasas/efectos de los fármacos , Monoéster Fosfórico Hidrolasas/metabolismo , Fósforo/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Suelo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Tetraciclina/metabolismo , Ureasa/efectos de los fármacos , Ureasa/metabolismo
18.
Exp Gerontol ; 43(5): 445-51, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18078731

RESUMEN

A large body of experimental research indicates that oxidative stress contributes to the processes related to aging and age-related diseases. Trace elements, particularly zinc (Zn), are essential components of the endogenous enzymatic antioxidant defenses. The aim of this study was to determine the activity of three main antioxidant enzymes in plasma [i.e. superoxide dismutase (pSOD), catalase (CAT), glutathione peroxidase (GPx)] and of SOD in erythrocyte (eSOD) in a group of 1108 healthy elderly subjects from different European countries. The same enzymatic activities were evaluated in a subgroup of 108 subjects before and after Zn supplementation. We observed that eSOD activity increased with age, whereas plasma Zn decreased. Moreover, we found that women showed higher eSOD activity and lower plasma Zn compared to men. There were no age and gender-related differences in the activities of pSOD, CAT and GPx. After Zn supplementation, the activities of Zn-dependent enzymes (pSOD and eSOD), as well as plasma Zn concentration, were significantly higher than before supplementation. These results were not influenced by age, gender, plasma Zn variations (Delta Zn) and geographic area. These data suggest the potential beneficial effects of Zn supplementation on Zn-dependent antioxidant enzymes in healthy elderly subjects.


Asunto(s)
Envejecimiento/metabolismo , Oxidorreductasas/efectos de los fármacos , Oligoelementos/farmacología , Zinc/farmacología , Anciano , Anciano de 80 o más Años , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Suplementos Dietéticos , Eritrocitos/enzimología , Femenino , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/metabolismo , Caracteres Sexuales , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Oligoelementos/administración & dosificación , Zinc/administración & dosificación , Zinc/deficiencia
19.
Altern Lab Anim ; 35(1): 111-8, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17411359

RESUMEN

Solid wastes from the oil-shale industry produce leachates containing toxic compounds such as heavy metals and persistent polycyclic aromatic hydrocarbons (PAH). The hazard to the environment represented by waste leachates depends not only on their chemical composition, but also on the mobility and bioavailability of toxic contaminants in soils. We evaluated the applicability of bioassays for toxicity assessment of the bioavailable fraction of heavy metals and PAH in soils, in experiments with samples of four different soil types (Rendzina, Brown pseudopodzolic, Typical brown, Sodpodzolic), the pH of which ranged from 6.2 to 7.2. The toxicity of the bioavailable fraction of the soil contaminants was assessed with the dehydrogenase enzyme activity assay, and with a Toxkit microbiotest with the crustacean, Thamnocephalus platyurus, after treatment of the soil samples with an artificial solution containing chromium (III), lead (II), copper (II), cadmium (II) and pyrene. The test results confirm those of earlier experiments, which characterised the sorption potential of investigated soils for the same compounds. Both tests turned out to be sufficiently sensitive, and hence can be recommended as effective and useful tools for the assessment of the bioavailable fraction of soil contaminants.


Asunto(s)
Bioensayo , Residuos Industriales/efectos adversos , Medición de Riesgo/métodos , Contaminantes del Suelo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Disponibilidad Biológica , Crustáceos/efectos de los fármacos , Crustáceos/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Indicadores y Reactivos/metabolismo , Residuos Industriales/análisis , Dosificación Letal Mediana , Metales Pesados/toxicidad , Oxazinas/metabolismo , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Petróleo , Hidrocarburos Policíclicos Aromáticos/toxicidad , Suelo/análisis , Contaminantes del Suelo/análisis , Pruebas de Toxicidad Aguda , Contaminantes Químicos del Agua/análisis , Xantenos/metabolismo
20.
Phytother Res ; 20(11): 1013-6, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16909446

RESUMEN

Ginkgo biloba from the traditional Chinese system of medicine has been found to possess neurocognitive enhancing effects. The mechanism of action of Ginkgo seems to be related to its antioxidant properties. In the present study, Ginkgo biloba phytosomes were administered to Wistar rats at 50 mg/kg and 100 mg/kg for 7 and 14 days. Chemical hypoxia was induced by administration of sodium nitrite (75 mg/kg) 1 h after the last administration of treatment. Thirty minutes after sodium nitrite administration, the animals were killed and the cerebral cortex, cerebellum, hippocampus and striatum were isolated and homogenized. The supernatants were used for the estimation of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Ginkgo biloba phytosome treatment was found to increase superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities in all the brain regions compared with those treated only with sodium nitrite. The prevention of depletion of the antioxidant enzymes by sodium nitrite in the presence of Ginkgo biloba phytosomes may be correlated to its antioxidant activity.


Asunto(s)
Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Ginkgo biloba/química , Oxidorreductasas/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Encéfalo/enzimología , Medicamentos Herbarios Chinos/farmacología , Femenino , Masculino , Oxidorreductasas/análisis , Ratas , Ratas Wistar , Nitrito de Sodio/administración & dosificación
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