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1.
Eur J Epidemiol ; 34(9): 853-861, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399939

RESUMO

Intake of individual antioxidants has been related to a lower risk of type 2 diabetes. However, the overall diet may contain many antioxidants with additive or synergistic effects. Therefore, we aimed to determine associations between total dietary antioxidant capacity and risk of type 2 diabetes, prediabetes and insulin resistance. We estimated the dietary antioxidant capacity for 5796 participants of the Rotterdam Study using a ferric reducing ability of plasma (FRAP) score. Of these participants, 4957 had normoglycaemia and 839 had prediabetes at baseline. We used covariate-adjusted proportional hazards models to estimate associations between FRAP and risk of type 2 diabetes, risk of type 2 diabetes among participants with prediabetes, and risk of prediabetes. We used linear regression models to determine the association between FRAP score and insulin resistance (HOMA-IR). We observed 532 cases of incident type 2 diabetes, of which 259 among participants with prediabetes, and 794 cases of incident prediabetes during up to 15 years of follow-up. A higher FRAP score was associated with a lower risk of type 2 diabetes among the total population (HR per SD FRAP 0.84, 95% CI 0.75; 0.95) and among participants with prediabetes (HR 0.85, 95% CI 0.73; 0.99), but was not associated with risk of prediabetes. Dietary FRAP was also inversely associated with HOMA-IR (ß - 0.04, 95% CI - 0.06; - 0.03). Effect estimates were generally similar between sexes. The findings of this population-based study emphasize the putative beneficial effects of a diet rich in antioxidants on insulin resistance and risk of type 2 diabetes.


Assuntos
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Resistência à Insulina , Avaliação Nutricional , Estado Pré-Diabético/metabolismo , Adulto , Idoso , Antioxidantes/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Fatores de Risco
3.
AAPS PharmSciTech ; 20(6): 250, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31297635

RESUMO

Melanoma is regarded as the fifth and sixth most common cancer in men and women, respectively, and it is estimated that one person dies from melanoma every hour in the USA. Unfortunately, the treatment of melanoma is difficult because of its aggressive metastasis and resistance to treatment. The treatment of melanoma continues to be a challenging issue due to the limitations of available treatments such as a low response rate, severe adverse reactions, and significant toxicity. Natural polyphenols have attracted considerable attention from the scientific community due to their chemopreventive and chemotherapeutic efficacy. It has been suggested that poorly soluble polyphenols such as curcumin, resveratrol, quercetin, coumarin, and epigallocatechin-3-gallate may have significant benefits in the treatment of melanoma due to their antioxidant, anti-inflammatory, antiproliferative, and chemoprotective efficacies. The major obstacles for the use of polyphenolic compounds are low stability and poor bioavailability. Numerous nanoformulations, including solid lipid nanoparticles, polymeric nanoparticles, micelles, and liposomes, have been formulated to enhance the bioavailability and stability, as well as the therapeutic efficacy of polyphenols. This review will provide an overview of poorly soluble polyphenols that have been reported to have antimetastatic efficacy in melanomas.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Melanoma/tratamento farmacológico , Polifenóis/administração & dosagem , Polifenóis/química , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/metabolismo , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/análogos & derivados , Catequina/química , Catequina/metabolismo , Curcumina/administração & dosagem , Curcumina/química , Curcumina/metabolismo , Humanos , Melanoma/metabolismo , Melanoma/prevenção & controle , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Polifenóis/metabolismo , Quercetina/administração & dosagem , Quercetina/química , Quercetina/metabolismo , Resveratrol/administração & dosagem , Resveratrol/química , Resveratrol/metabolismo , Neoplasias Cutâneas/metabolismo , Solubilidade
4.
Medicine (Baltimore) ; 98(29): e15404, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335666

RESUMO

This study retrospectively evaluated the effect of lutein supplement (LS) on patients with non-proliferative diabetic retinopathy (NPDR).A total of 72 patients with NPDR were included in this study. All patients received Zeaxanthin during the study period. In addition, 36 patients also received LS and were assigned to the treatment group, while the other 36 patients did not receive LS and were assigned to the control group. All patients were treated for a total of 4 months. The endpoints included visual acuity (VA), contrast sensitivity (CS), and glare sensitivity (GS). In addition, any adverse events were also assessed. All endpoints were measured before and after 4-month treatment.Before treatment, there were no significant differences in VA (P = .75), CS (P = .71), and GS (P = .73) between two groups. After 4-month treatment, there were still no significant differences in all endpoints of VA (P = .66), CS (P = .58), and GS (P = .61) between two groups. No adverse events were recorded in either group.The results of this retrospective study showed that LS may not benefit for patients with NPDR after 4-month treatment. More high quality randomized controlled trials should still be needed to warrant the results of this study.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Luteína , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Sensibilidades de Contraste , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Suplementos Nutricionais , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Luteína/administração & dosagem , Luteína/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos
5.
J Agric Food Chem ; 67(31): 8609-8616, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31314514

RESUMO

Quercetin (QUE)-loaded nanoparticles (QCG-NPs) were fabricated by ionic gelation between chitosan (CS) and gum arabic (GA) at pH 3.5. At constant CS (0.5 mg/mL) and QUE (60 µM) concentrations, QCG-NPs (260-490 nm) were prepared uniformly with 0.8-2.2 mg/mL GA and exhibited high QUE encapsulation efficiency (94.8-98.0%) and sustained QUE release (4.42-8.89% after 8 h). Because of the electrostatic interaction between QCG-NPs and the mucin layer, in vitro mucin and cell adhesion of QUE were significantly (p < 0.05) enhanced in QCG-NPs (0.44-0.48 mg/mL and 31.7-78.5%), respectively, and the adhesiveness was significantly (p < 0.05) increased with an increase of GA. Because particle size and adhesion properties affect the surface area and retention time of QCG-NPs at the absorption site, cell permeation of QUE through simple diffusion by QCG-NPs exhibited the same tendency as the adhesion results. These data were verified in cellular antioxidant and in vivo ferric reducing abilities of plasma assays that evaluated the antioxidant activities of QUE absorbed into an intestinal cell model and rat blood, respectively. The results provide a better understanding of QCG-NP absorption and indicate that QCG-NPs with mucoadhesion properties can be an effective delivery system for improving QUE absorption.


Assuntos
Antioxidantes/química , Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Mucosa Intestinal/metabolismo , Nanopartículas/química , Quercetina/química , Quercetina/metabolismo , Animais , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Células CACO-2 , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Humanos , Tamanho da Partícula , Quercetina/administração & dosagem , Ratos , Ratos Sprague-Dawley
6.
Expert Opin Investig Drugs ; 28(7): 593-603, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31185180

RESUMO

INTRODUCTION: Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target essential pathways of OST in many pathological conditions. The pharmacological parameters required by antioxidant drugs in relation to the OST target characteristics include the determination of the therapeutic index, ADMET and drug interactions. Antioxidant drug development efforts are currently targeting the treatment of severe diseases with no proven effective therapies. AREAS COVERED: This article addresses the damaging effects of OST, prospects for the development of pharmaceutical antioxidants and clinical studies using other drugs with antioxidant potential. EXPERT OPINION: Effective antioxidant therapeutic strategies should include the design of protocols for the inhibition of OST through iron chelation, administration of synthetic and natural antioxidants and enhancement of the antioxidant defences by increasing the production of endogenous antioxidants and activation of antioxidant mechanisms. Different therapeutic strategies apply in the use of antioxidant drugs for one or more targets, for prevention, treatment, or of post-treatment effects and for systematic, long-term or short-term applications. The design of new antioxidant drugs and effective protocols which can include Deferiprone and N-acetylcysteine combinations, could lead to the development of a new class of therapeutics for clinical use.


Assuntos
Antioxidantes/farmacologia , Depuradores de Radicais Livres/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Animais , Antioxidantes/administração & dosagem , Deferiprona/administração & dosagem , Deferiprona/farmacologia , Desenho de Drogas , Desenvolvimento de Medicamentos/métodos , Depuradores de Radicais Livres/administração & dosagem , Radicais Livres , Humanos , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/farmacologia , Terapia de Alvo Molecular
7.
Br Poult Sci ; 60(3): 279-287, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146535

RESUMO

1. This study analysed whether in ovo injection of ascorbic acid before incubation and at high incubation temperature influenced blood characteristics and performance in broilers reared in different temperature conditions. 2. A total of 3,000 fertile eggs from broiler breeders (Cobb®) were randomly divided into three incubation treatments: no ascorbic acid injection and egg incubation at 37.5°C (control); no ascorbic acid injection and egg incubation at 39°C; in ovo ascorbic acid injection prior to incubation (6 µg AA/100 µl water) and egg incubation at 39°C. 3. Male chicks hatched from the three incubation treatments were submitted to three distinct rearing temperatures (control, cold and hot) from the third week of age onwards (540 chicks were divided into 6 treatments with 5 replicates per treatment). 4. Measurements at 42 d showed that, after egg incubation at 39°C, the haematocrit, haemoglobin values, ionised calcium and glucose concentrations were increased and base excess values were reduced. However, in ovo injection of ascorbic acid normalised all these parameters. 5. Partial CO2 and O2 pressure were higher with increased rearing temperature. Blood pH was lower when eggs were incubated at 39°C and injected with ascorbic acid. In ovo injection of ascorbic acid induced leucocytosis due to lymphocytosis and heterophilia, restored basophils rate and led to monocytopoenia. Leucocytosis was triggered by hot rearing temperature due to lymphocytosis, eosinophilia and heterophilia. 6. The results obtained in this study showed that in ovo injection of ascorbic acid before incubation may serve as a long-term stimulator and modulator of the broiler immune system, and that high incubation temperatures induce adaptations in the electrolytic balance, minimising or avoiding the occurrence of respiratory alkalosis under hot rearing temperature.


Assuntos
Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Galinhas/metabolismo , Temperatura Alta , Óvulo/química , Animais , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Análise Química do Sangue , Galinhas/sangue , Testes Hematológicos , Injeções/veterinária , Masculino
8.
BMC Complement Altern Med ; 19(1): 129, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196040

RESUMO

BACKGROUND: Green tea has polyphenols like flavonoids and catechins; mainly epigallocatechin-3-gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC), out of which EGCG is of higher abundance. EGCG has shown preventive role in hypercholesterolemia. However, due to low oral bioavailability, a need arises to improve its membrane permeability and transporter-mediated intestinal efflux. Therefore, an attempt was made to enhance permeability and bioavailability of EGCG using curcumin to treat hyperlipidemia. Further, it was formulated in herbal tea bags to achieve patient compliance. METHODS: EGCG extracted from green tea leaves was confirmed by High Performance Thin Layer Chromatography. Green tea extract (GTE), curcumin and their mixtures were subjected to Fourier Transform Infra-Red spectroscopy and Differential Scanning Calorimetry for compatibility studies. Powder formulation was prepared comprising GTE, curcumin, sucralose and cardamom. RESULTS: Ex-vivo study was performed on everted goat intestine, analyzed by HPLC and demonstrated highest permeation of GTE:curcumin (220:50) (53.15%) than GTE (20.57%). Antihyperlipidemic activity was performed in rats for 15 days. Blood sample analysis of rats of test groups (formulation and GTE solution) fed on high fat diet showed (mg/dl):cholesterol 80 and 90, triglycerides 73.25 and 85.5, HDL 50.75 and 46, LDL 43.9 and 46, VLDL 14.65 and 17.1 respectively with significant lipid regulating effect. CONCLUSION: Curcumin enhanced permeability of EGCG. Therefore, P-glycoprotein pump inside intestine can be potential mechanism to enhance permeability of EGCG. Thus, EGCG-curcumin herbal tea bag is promising nutraceutical to treat hyperlipidemia in day-to-day life achieving patient compliance.


Assuntos
Antioxidantes/farmacocinética , Catequina/análogos & derivados , Curcumina/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Masculino , Permeabilidade , Fitoterapia , Ratos Sprague-Dawley , Chá
9.
Int. j. morphol ; 37(2): 428-437, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002239

RESUMO

Oxidative stress and inflammation are the key players in the development of motor dysfunction post-spinal cord ischemic reperfusion injury (SC-IRI). This study investigated the protective effect of concomitant pre-administration of melatonin and alpha-tocopherol on the early complications (after 48 hours) of spinal cord IRI injury in rats. Melatonin or α-tocopherol were preadministered either individually or in combination for 2 weeks, then rats were exposed SC-IRI. Neurological examinations of the hind limbs and various biochemical markers of oxidative stress and inflammation in the SC tissue were assessed. Solely pre-administration of either melanin or α-tocopherol significantly but partially improved motor and sensory function of the hind limbs mediated by partial decreases in SC levels of MDA, AOPP and PGE2 levels and activities of SOD, partial significant decreases in plasma levels of total nitrate/nitrite and significant increases in AC activity of GSH-Px. However, combination therapy of both drugs resulted in the maximum improvements in all neurological assessments tested and biochemical endpoints. In conclusion, by their synergistic antioxidant and antiinflammatory actions, the combination therapy of melatonin and α-tocopherol alleviates SC-IRI induced paraplegia.


El estrés oxidativo y la inflamación son claves en el desarrollo de la disfunción motora posterior a lesión isquémica de la médula espinal (SC-IRI). Este estudio investigó acerca del efecto protector de la administración previa concomitante de la melatonina y alfa-tocoferol en las complicaciones tempranas (después de 48 horas) de la lesión de IRI de la médula espinal en ratas. La melatonina o el α-tocoferol se administraron individualmente o en combinación durante 2 semanas, luego las ratas fueron expuestas a SC-IRI. Se evaluaron los exámenes neurológicos de las miembros pélvicos y diversos marcadores bioquímicos de estrés oxidativo e inflamación en el tejido subcutáneo. Solo la administración previa de melatonina o α-tocoferol mejoró parcial y significativamente la función motora y sensorial de los miembros pélvicos mediadas por disminuciones parciales en los niveles de SC de los niveles de MDA, AOPP y PGE2 y las actividades de la SOD, disminuciones significativas parciales en los niveles plasmáticos del total nitrato / nitrito y aumentos significativos en la actividad de AC de GSH-Px. Sin embargo, se observaron los mejores resultados durante la combinación de ambos fármacos en todas las evaluaciones neurológicas y en los puntos finales bioquímicos. En conclusión, debido a sus acciones antioxidantes y antiinflamatorias sinérgicas, la terapia de melatonina y α-tocoferol alivia la paraplejía inducida por SC-IRI.


Assuntos
Animais , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia do Cordão Espinal/tratamento farmacológico , Melatonina/administração & dosagem , Antioxidantes/administração & dosagem , Paraplegia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Dinoprostona/sangue , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Tocoferóis/farmacologia , Melatonina/farmacologia , Nitritos/sangue , Antioxidantes/farmacologia
10.
Microsc Res Tech ; 82(9): 1430-1437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31099952

RESUMO

This article presents the results of experiments, which examine cell mechanisms with the goal of confirming the effective action of the active ingredients used in anti-aging cosmetics. Skin stiffness measurements with the use of an atomic force microscope on two forms of vitamin C (ascorbyl tetraisopalmitate and l-ascorbic acid) have been presented. The estimated Young's modulus for three types of cells (a control as well as cells treated with two forms of vitamin C) has shown significant differences in the stiffness of the tested cells which was confirmed in the histological staining experiment. The presented results indicate the dependence between collagen synthesis and the stiffness of cells treated with two forms of vitamin C.


Assuntos
Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Cosméticos/química , Microscopia de Força Atômica , Higiene da Pele/métodos , Vitaminas/administração & dosagem , Animais , Linhagem Celular , Elasticidade , Camundongos , Resultado do Tratamento
11.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071925

RESUMO

Current organ shortages have led centers to extend the acceptance criteria for organs, increasing the risk for adverse outcomes. Current preservation protocols have not been adapted so as to efficiently protect these organs. Herein, we target oxidative stress, the key mechanism of ischemia reperfusion injury. Vectisol® is a novel antioxidant strategy based on the encapsulation of resveratrol into a cyclodextrin, increasing its bioavailability. We tested this compound as an additive to the most popular static preservation solutions and machine perfusion (LifePort) in a preclinical pig model of kidney autotransplantation. In regard to static preservation, supplementation improved glomerular filtration and proximal tubular function early recovery. Extended follow-up confirmed the higher level of protection, slowing chronic loss of function (creatininemia and proteinuria) and the onset of histological lesions. Regarding machine perfusion, the use of Vectisol® decreased oxidative stress and apoptosis at the onset of reperfusion (30 min post declamping). Improved quality was confirmed with decreased early levels of circulating SOD (Superoxide Dismutase) and ASAT (asparagine amino transferase). Supplementation slowed the onset of chronic loss of function, as well as interstitial fibrosis and tubular atrophy. The simple addition of Vectisol® to the preservation solution significantly improved the performance of organ preservation, with long-term effects on the outcome. This strategy is thus a key player for future multi-drug therapy aimed at ischemia reperfusion in transplantation.


Assuntos
Antioxidantes/administração & dosagem , Transplante de Rim/efeitos adversos , Rim/fisiopatologia , Resveratrol/química , Transplante Autólogo , Animais , Antioxidantes/química , Ciclodextrinas/administração & dosagem , Ciclodextrinas/química , Modelos Animais de Doenças , Composição de Medicamentos , Humanos , Rim/efeitos dos fármacos , Preservação de Órgãos/métodos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/fisiopatologia , Resveratrol/administração & dosagem , Solubilidade , Suínos
12.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072023

RESUMO

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete's health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances.


Assuntos
Antioxidantes/administração & dosagem , Desempenho Atlético , Beta vulgaris/química , Nitratos/administração & dosagem , Adolescente , Adulto , Antioxidantes/química , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/urina , Suplementos Nutricionais , Feminino , Sucos de Frutas e Vegetais , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/química , Nitratos/urina , Nitritos/urina , Compostos Nitrosos/urina , Raízes de Plantas/química , Adulto Jovem
13.
Environ Sci Pollut Res Int ; 26(20): 20631-20653, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104231

RESUMO

The aim of this study relates to the modulatory role of ferulic acid (FA) against cadmium (Cd)-induced oxidative stress in the liver and kidney of male Wistar albino rats. Cd is an extremely toxic industrial and environmental pollutant and is well known for its varied toxic clinical manifestations. FA is a derivative of curcumin and a ubiquitous phenolic compound having a wide range of therapeutic activities. In the current study, Cd (10 mg/kg) was administered subcutaneously for 15 and 30 days to induce hepato-renal toxicity. Cd concentration was found to be significantly high in Cd-intoxicated rats (liver > kidney) while the supplementation of FA (50 mg/kg) significantly reduces the Cd concentration in liver and kidney tissues. Reduced body and organ weights and food and water consumption and increased rectal temperature were noticed in Cd-treated rats while these parameters were significantly ameliorated in FA-supplemented rats. Liver and kidney damage induced by Cd was significantly revealed by the reduction in serum total protein contents (TPC) and increased activities of serum nitric oxide (NO) levels and hepato-nephrotoxicity marker enzymes, namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), AST:ALT ratio, uric acid, urea, urea nitrogen, and creatinine, along with the increased levels of hepatic and renal oxidative stress markers, namely lipid peroxidation (MDA levels), lipid hydroperoxides (LOOH), protein carbonyl content (PCC), total oxidant status (TOS), and oxidative stress index (OSI) in liver and kidney tissues. In addition, the toxicity of Cd was also evidenced by a significant decrease in the levels of total thiols (TTH), total antioxidant concentration (TAC), enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and non-enzymatic antioxidants (reduced glutathione (GSH) and total free sulfhydryl groups (TSH)). Administration of FA significantly restored the serum total protein levels and activities of serum NO levels and hepatic and renal marker enzymes to normal levels in comparison with Cd-intoxicated rats. Furthermore, FA significantly reduced the oxidative stress markers and recuperated the levels of antioxidant defense in the liver and kidney as evidenced by native PAGE and spectrophotometric assays, correlation and regression analysis and multivariate analysis of variance (MANOVA), and inferring the antioxidant role of FA. Histopathological damage due to Cd intoxication in the liver and kidney is demonstrated as vasodilatation and congestion in central veins and sinusoids as well as around the glomerulus, infiltration of mixed inflammatory cells and peripheral hemorrhage, hemorrhagic and enlarged sinusoids, disorganization of the hepatic parenchyma, focal necrosis, swelling of hepatocytes, calcified tissue inside blood vessels, hepatocyte degeneration and vacuolization of liver cells, hyaline casts, degenerated glomerulus with wide space and detached basement membrane, distal tubule with wide lumen, deformed proximal tubules with detached brush border, and degeneration and hyalinization of glomerular tuft. But, FA significantly reduced the toxicity of Cd and protected the normal histological architecture of the liver and kidney tissues. Cd-intoxicated rats were associated with a significant upregulation of TNF-α, COX-2, and HSP70 proteins, whereas treatment with FA caused downregulation of the above inflammatory markers indicating the anti-inflammatory role of FA. Principal component analysis (PCA) and Euclidean similarity measure studies clearly indicate that the liver is more prone to Cd toxicity than the kidney and FA supplementation significantly prevents oxidative stress, augmenting antioxidative status, and regaining histological parameters of the liver and kidney to normal, indicating hepato-nephroprotective, antiradical, antioxidant, and anti-inflammatory effects of this phenolic compound.


Assuntos
Antioxidantes/farmacologia , Cádmio/toxicidade , Ácidos Cumáricos/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Biomarcadores/metabolismo , Suplementos Nutricionais , Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos Wistar
14.
J Food Sci ; 84(6): 1600-1608, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31132143

RESUMO

Considering the anti-photoaging effect of antioxidant compounds, we investigated the protective capacity of grape peel extract (GPE) and resveratrol on ultraviolet (UV)-induced skin wrinkle formation. Total phenolic, total anthocyanin, and total flavonoid content in GPE prepared from peel of Campbell Early variety were 23.96 ± 0.09, 3.27 ± 0.40, and 1.24 ± 0.09 mg/g dry weight, respectively. Additionally, trans-resveratrol and piceid content of the resulting GPE were 117.14 ± 19.97 and 85.23 ± 8.89 µg/g dry weight, respectively. Oral administration of either 2 g GPE or 2 mg resveratrol per kg body weight in mice attenuated UVB-induced epidermal thickening (the thickness was reduced by about 63% and 55% with GPE and resveratrol consumption prior to exposure to UVB, respectively, compared to only UVB-treated condition) and had marginally protective effect on wrinkle formation of skin exposed to UVB. As introduction of either GPE or resveratrol induced Nrf2-dependent antioxidant enzymes including heme oxygenase-1 (HO-1) in liver and skin as well as inhibited metalloproteinases, it is highly probable that the extract or resveratrol mitigated UVB-induced photoaging through activation of Nrf2/HO-1 signaling pathway. PRACTICAL APPLICATION: This study proved that resveratrol and the extract of grape peel, a common by-product of grape juice processing, provide effective protection from UV-induced skin wrinkle formation. Therefore, grape peel extract, which contains an appreciable amount of bioactive compound resveratrol, can be utilized as functional food ingredient for the manufacture of inner beauty products.


Assuntos
Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/administração & dosagem , Resveratrol/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Vitis/química , Animais , Antioxidantes/administração & dosagem , Modelos Animais de Doenças , Feminino , Flavonoides/administração & dosagem , Flavonoides/análise , Frutas/química , Glucosídeos/administração & dosagem , Glucosídeos/análise , Heme Oxigenase-1/genética , Humanos , Camundongos , Camundongos Pelados , Fator 2 Relacionado a NF-E2/genética , Resveratrol/análise , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Envelhecimento da Pele/genética , Envelhecimento da Pele/efeitos da radiação , Estilbenos/administração & dosagem , Estilbenos/análise , Raios Ultravioleta
15.
Oxid Med Cell Longev ; 2019: 7218936, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049136

RESUMO

Nitrate (NO3 -) supplementation is associated with exercise performance, oxygen uptake, blood flow, and blood pressure improvement, and it can act as an antioxidant agent. This study evaluated the effects of sodium nitrate supplementation on oxidative stress markers and blood pressure responses after aerobic exercise performance in physically active males. Fourteen subjects aged 22 ± 3 years and with a BMI of 23 ± 1 kg/m2 were submitted to four exercise tests in intervals of 5 days. Nitrate supplementation (NO session) and placebo supplementation (PL session) were acute (AC) and over a period of 5 days (FD) in random order with a crossover design. Saliva was collected at basal (0'); 60 min after supplementation (60'); immediately after exercise (90'); and 15, 30, and 60 min after the test (105', 120', and 150'). The NO session had higher concentrations (P < 0.05) of salivary nitrite in both AC and FD treatments when compared with the PL session. There was a reduction in systolic blood pressure (SBP) only after FD in the NO session. Furthermore, uric acid and total antioxidant capacity (FRAP) salivary concentrations increased, while SOD activity and TBARS levels decreased after FD but not after AC in the NO session. The results suggest that nitrate supplemented over a period of 5 days reduced SBP and indirectly acted as an antioxidant in healthy nonsedentary young men.


Assuntos
Antioxidantes/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Nitratos/administração & dosagem , Adulto , Estudos Cross-Over , Exercício/fisiologia , Teste de Esforço , Humanos , Masculino , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Saliva/metabolismo
16.
Food Chem Toxicol ; 131: 110531, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31136780

RESUMO

1-O-(4-hydroxymethylphenyl)-α-L-rhamnopyranoside (MPG) is a phenolic glycoside that exists in Moringa oleifera seeds with various health benefits, whereas its hepatoprotective effect is lacking clarification. Herein, MPG was isolated from Moringa oleifera seeds, and its hepatoprotection against CCl4-induced hepatotoxicity in L02 cells and ICR mice was investigated. Toxicity studies showed that MPG did not induce significant changes in organ coefficients and histological analysis, as well as exhibited no cytotoxicity. In vitro studies indicated that MPG substantially increased cell viability and intracellular SOD activities, and significantly inhibited LDH leakage in CCl4-treated cells. In vivo studies demonstrated that MPG significantly alleviated CCl4-induced hepatotoxicity in mice, as indicated by diagnostic indicators of hepatic injury, as well as the histopathological analysis. Moreover, MPG reduced the lipid peroxidation levels and regulated the inflammatory cytokines. Notably, MPG substantially suppressed the significant elevation of ROS production in hepatocytes of mice intoxicated with CCl4. Moreover, TUNEL assay demonstrated that MPG obviously inhibited hepatic apoptosis induced by CCl4. Altogether, these results suggested that MPG has excellent liver-protecting effects against hepatocytotoxicity induced by CCl4 in mice and L02 cells, which can be further developed as a valuable functional food additive or drug for the treatment of hepatic injury.


Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glicosídeos/farmacologia , Moringa oleifera/química , Sementes/química , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Tetracloreto de Carbono/toxicidade , Linhagem Celular , Citocinas/metabolismo , Feminino , Glicosídeos/administração & dosagem , Glicosídeos/isolamento & purificação , Glicosídeos/toxicidade , Fígado/patologia , Masculino , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos
17.
AAPS PharmSciTech ; 20(5): 181, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31049748

RESUMO

Resveratrol (RES) is a potent antioxidant used for the management of several central nervous system diseases. RES bioavailability is less than 1 owing to its low solubility and extensive intestinal and hepatic metabolism. The aim of the study was to enhance RES bioavailability through developing intranasal transferosomal mucoadhesive gel. Reverse evaporation-vortexing sonication method was employed to prepare RES-loaded transferosomes. Transferosomes were developed via 34 definitive screening design, using soya lecithin, permeation enhancers, and surfactants. The optimized formula displayed spherical shape with vesicle size of 83.79 ± 2.54 nm and entrapment efficiency (EE%) of 72.58 ± 4.51%. Mucoadhesive gels were prepared and evaluated, then optimized RES transferosomes were incorporated into the selected gel and characterized using FTIR spectroscopy, in vitro release, and ex vivo permeation study. Histopathological examination of nasal mucosa and in vivo pharmacokinetic study were conducted. In vitro drug release from transferosomal gel was 65.87 ± 2.12% and ex vivo permeation was 75.95 ± 3.19%. Histopathological study confirmed the safety of the optimized formula. The Cmax of RES in the optimized RES trans-gel was 2.15 times higher than the oral RES suspension and AUC(0-∞) increased by 22.5 times. The optimized RES trans-gel developed intranasal safety and bioavailability enhancement through passing hepatic and intestinal metabolism.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Encéfalo/metabolismo , Resveratrol/administração & dosagem , Resveratrol/farmacocinética , Adesivos , Administração Intranasal , Animais , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Géis , Masculino , Mucosa Nasal/metabolismo , Ratos , Ratos Wistar
18.
Anticancer Res ; 39(5): 2453-2458, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092439

RESUMO

BACKGROUND/AIM: Cisplatin is a highly effective chemotherapeutic agent that is used to treat solid tumors; however, its severe side effects remain a limitation. In particular, the high incidence of cisplatin-induced ototoxicity has attracted interest. Melatonin has been shown to decrease the toxic effects of cisplatin due to its antioxidant activity, and could increase the efficacy of cancer chemotherapy. The aim of this study was to determine the effect of melatonin against ototoxicity in rats treated with cisplatin. MATERIALS AND METHODS: Rats were randomly divided into four groups (saline, melatonin, cisplatin+saline, and melatonin+cisplatin). Distortion-product otoacoustic emission (DPOAE) measurements were carried out on days 1 and 8. RESULTS: There was a decrease in DPOAE amplitudes in the animals that received cisplatin (10 mg/kg); however, the group treated with cisplatin+melatonin presented DPOAE amplitudes comparable to those of the control groups. CONCLUSION: Melatonin can be used as an adjuvant tumor treatment due to its ability to decrease cisplatin-induced ototoxicity.


Assuntos
Antioxidantes/administração & dosagem , Melatonina/administração & dosagem , Neoplasias/tratamento farmacológico , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Modelos Animais de Doenças , Humanos , Neoplasias/patologia , Emissões Otoacústicas Espontâneas/fisiologia , Ratos
19.
Medicina (Kaunas) ; 55(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991760

RESUMO

BACKGROUND AND OBJECTIVES: Cucumis melo, of family Cucurbitaceae, has traditionally been used to treat variety of kidney disorders. However to best of our knowledge there is no scientific study available that validates its renaoprotective uses. Therefore, this study aimed to evaluate nephroprotective effects of hydroalcoholic extract of Cucumis melo seeds (CMHE) and to identify its phytoconstituents. MATERIALS AND METHODS: HPLC was performed to identify key phytochemicals of CMHE. Gentamicin (100 mg/kg/day, i.p) was administered to induce nephrotoxicity in Swiss albino mice for 8 days. Gentamicin (100 mg/kg/day, i.p) and oral CMHE were co-administered to mice at doses of 250 and 500 mg/kg to evaluate protective effects of CMHE. Normal control group mice were administered normal saline. Changes in body weights, biochemical and histopathological studies were conducted to establish nephroprotective effects of CMHE. Results: HPLC analysis indicated presence of quercetin, m-coumaric acid, gallic acid, chlorogenic acid, and trans-4-hydroxy-3-methoxy cinnamic acid in CMHE. Mice treated with CMHE showed significant increase in body weight and decrease in kidney weight as compared with toxic control group. Dose-dependent significant decrease in total blood urea nitrogen, serum creatinine, serum urea, and uric acid levels were observed in CMHE-treated groups as compared with toxic control group. Histopathological analysis of CMHE-treated groups showed improvement in kidney structures as compared with toxic control group. Conclusions: Biochemical, histopathological, and phytochemical screening of hydroalcoholic extract of Cucumis melo seeds suggest that it has nephroprotective potential. Furthermore, standardization of extract against identified phytochemicals, as well as long-term toxicological studies are suggested before commencement of clinical trials.


Assuntos
Antioxidantes/análise , Antioxidantes/uso terapêutico , Cucumis melo/química , Nefropatias/tratamento farmacológico , Fitoterapia/efeitos adversos , Extratos Vegetais/análise , Extratos Vegetais/uso terapêutico , Sementes/química , Análise de Variância , Animais , Antioxidantes/administração & dosagem , Peso Corporal , Cromatografia Líquida de Alta Pressão , Creatinina/sangue , Gentamicinas , Nefropatias/induzido quimicamente , Nefropatias/patologia , Camundongos , Paquistão , Extratos Vegetais/administração & dosagem , Resultado do Tratamento , Ureia/sangue , Ácido Úrico/análise
20.
Phytomedicine ; 59: 152763, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004882

RESUMO

BACKGROUND: Hypericum perforatum is used in ethnopharmacology and has recently become popular in conventional medicine for treatment of mild to moderate depression. The abundance of potentially functional phytochemicals and their broader utilizations in traditional medicine suggests that ingestion of H. perforatum may impart additional secondary health benefits. HYPOTHESIS/PURPOSE: Considering that many phytochemicals are known to display antioxidant activity, it was hypothesized that H. perforatum ingestion may inhibit oxidative stress and inflammation (OSI) which occurs in transient cycles following exercise and consumption of meals. The aim of this study was to explore the pharmacokinetics of H. perforatum phytochemicals after ingestion to predict the absorption timing of putative medicinal phytochemicals. STUDY DESIGN/METHODS: In silico analyses of previously published plant extract phytochemical profiles were performed, wherein the Phytochemical Absorption Prediction (PCAP) model was used to predict the pharmacokinetics of phytochemicals. The predicted times for phytochemicals to reach maximum plasma concentration (Tmax), and associated antioxidant activities, were compared to prior clinical in vivo studies to assess the accuracy and applicability of predictions. RESULTS: The PCAP model identified that phytochemicals with antioxidant activity concurrently accumulate in plasma with Tmax in the range of 1.6-2.3 h after ingestion. Comparison with previously published results identified that attenuation of OSI following H. perforatum ingestion aligns with the predicted Tmax of antioxidant phytochemicals. CONCLUSION: Based on these results it is therefore recommended that H. perforatum administration occurs 2 h before meals to provide optimal secondary health benefits associated with inhibition of postprandial stress. Additionally, these results highlight the use of in silico analyses to inform ingestion time and optimize the health benefits from ingestion of plant-based foods and medicines.


Assuntos
Antioxidantes/farmacocinética , Hypericum/química , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/farmacocinética , Extratos Vegetais/farmacocinética , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Humanos , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/sangue , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Extratos Vegetais/farmacologia
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