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1.
Toxins (Basel) ; 12(9)2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899405

RESUMO

Lipid aldehydes originating from the peroxidation of n-3 and n-6 polyunsaturated fatty acids are increased in hemodialysis (HD) patients, a process already known to promote oxidative stress. However, data are lacking for patients with chronic kidney disease (CKD) before the initiation of HD. We prospectively evaluated the changes of plasma concentrations of two major lipid aldehydes, 4-HHE and 4-HNE, according to the decrease of glomerular filtration rate (GFR) in 40 CKD and 13 non-CKD participants. GFR was measured by inulin or iohexol clearance. Thus, 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE) were quantitated in plasma by gas chromatography coupled with mass spectrometry and their covalent adducts on proteins were quantified by immunoblotting. On the one hand, 4-HHE plasma concentration increased from CKD stage I-II to CKD stage IV-V compared to non-CKD patients (4.5-fold higher in CKD IV-V, p < 0.005). On the other hand, 4-HNE concentration only increased in CKD stage IV-V patients (6.2-fold, p < 0.005). The amount of covalent adducts of 4-HHE on plasma protein was 9.5-fold higher in CKD patients than in controls (p < 0.005), while no difference was observed for 4-HNE protein adducts. Plasma concentrations of 4-HNE and 4-HHE are increased in CKD IV-V patients before the initiation of hemodialysis.


Assuntos
Aldeídos/sangue , Biomarcadores/sangue , Peroxidação de Lipídeos , Estresse Oxidativo , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Regulação para Cima
2.
Free Radic Biol Med ; 131: 115-125, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508576

RESUMO

Lipid peroxidation is one of the earliest pathogenic events of non-alcoholic fatty liver disease (NAFLD). In this context, an increased oxidation of the lipoperoxyl radical scavenger α-tocopherol (α-TOH) should occur already in the subclinical phases of the disease to compensate for the increase oxidation of the lipid excess of liver and possibly of other tissues. However, this assumption remains unsupported by direct analytical evidence. In this study, GC-MS/MS and LC-MS/MS procedures have been developed and applied for the first time to measure the vitamin E oxidation metabolite α-tocopheryl quinone (α-TQ) in plasma of fatty liver (FL) subjects that were compared in a pilot cross-sectional study with healthy controls. The protein adducts of 4-hydroxynonenal (4-HNE) and the free form of polyunsaturated free fatty acids (PUFA) were measured as surrogate indicators of lipid peroxidation. α-TQ formation was also investigated in human liver cells after supplementation with α-TOH and/or fatty acids (to induce steatosis). Compared with controls, FL subjects showed increased (absolute and α-TOH-corrected) levels of plasma α-TQ and 4-HNE, and decreased concentrations of PUFA. α-TQ levels positively correlated with indices of liver damage and metabolic dysfunction, such as alanine aminotransferase, bilirubin and triglycerides, and negatively correlated with HDL cholesterol. Fatty acid supplementation in human hepatocytes stimulated the generation of cellular oxidants and α-TOH uptake leading to increased α-TQ formation and secretion in the extracellular medium - both were markedly stimulated by α-TOH supplementation. In conclusion, plasma α-TQ represents an early biomarker of the lipoperoxyl radical-induced oxidation of vitamin E and lipotoxicity of the fatty liver.


Assuntos
Ácidos Graxos Insaturados/sangue , Sequestradores de Radicais Livres/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Vitamina E/análogos & derivados , alfa-Tocoferol/sangue , Adulto , Alanina Transaminase/sangue , Aldeídos/sangue , Bilirrubina/sangue , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Cromatografia Gasosa-Espectrometria de Massas , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Peroxidação de Lipídeos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Projetos Piloto , Triglicerídeos/sangue , Vitamina E/sangue , alfa-Tocoferol/administração & dosagem
3.
Mol Cell Biochem ; 434(1-2): 51-60, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28432552

RESUMO

Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.


Assuntos
Anabolizantes/farmacologia , Biomarcadores/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Imobilização , Nandrolona/administração & dosagem , Estresse Oxidativo , Estresse Fisiológico , Aldeídos/sangue , Aldeídos/metabolismo , Aminoácidos/biossíntese , Animais , Biomarcadores/sangue , Western Blotting , Eletroforese em Gel Bidimensional , Metabolismo Energético , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Espectrometria de Massas , Ratos , Ratos Sprague-Dawley
4.
Anal Biochem ; 524: 31-44, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-27530652

RESUMO

Here, we report the simultaneous derivatization and quantification of malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE) in human plasma by GC-MS/MS using [1,3-2H2]-MDA (d2-MDA) and [9,9,9-2H3]-HNE (d3-HNE) as the internal standards, respectively. MDA, d2-MDA, HNE and d3-HNE were converted to their pentafluorobenzyl oximes (PFBOX) by pentafluorobenzyl hydroxylamine. Subsequently, the hydroxyl groups of the PFBOX of HNE and d3-HNE were trimethylsilylated with N,O-bis(trimethylsilyl)trifluoroacetamide/1% trimethylchlorosilane. GC-MS/MS analyses were performed in the electron-capture negative-ion chemical ionization mode. Quantification was performed by selected-reaction monitoring the mass transitions m/z 442 to m/z 243 for MDA, m/z 444 to m/z 244 for d2-MDA, m/z 403 → m/z 283 for HNE and m/z 406 → m/z 286 for d3-HNE. The method was applied to measure MDA and HNE in plasma of patients suffering from coronary artery disease (CAD) or peripheral artery occlusive disease (PAOD) before and after oral supplementation of L-arginine (3 g/day) or placebo for 3 (CAD and PAOD) and 6 months (PAOD). All plasma samples were analyzed after completion of the studies. Our results revealed that storage of plasma samples (at -80 °C) leads to lower MDA and HNE plasma concentrations in the plasma samples that were collected at the end of the studies as compared to those collected at the begin of the studies. Based on MDA and HNE measurements in plasma, L-arginine did not influence lipid peroxidation in CAD and PAOD patients. Long-term studies on lipid peroxidation are best performed by measuring oxidative stress biomarkers such as MDA and/or HNE in plasma samples immediately after their collection. Long-term storage of plasma samples even at -80 °C is not recommended.


Assuntos
Aldeídos/sangue , Cromatografia Gasosa-Espectrometria de Massas/métodos , Malondialdeído/sangue , Estresse Oxidativo , Biomarcadores/sangue , Humanos
5.
J Clin Neurosci ; 35: 104-108, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27697434

RESUMO

Traumatic brain injury (TBI) encompasses a broad range of injury mechanisms and severity. A detailed determination of TBI severity can be a complex challenge, with current clinical tools sometimes insufficient to tailor a clinical response to a spectrum of patient needs. Blood biomarkers of TBI may supplement clinical assessments but currently available biomarkers have limited sensitivity and specificity. While oxidative stress is known to feature in damage mechanisms following TBI, investigation of blood biomarkers of oxidative stress has been limited. This exploratory pilot study of a subset of 18 trauma patients with TBI of varying severity, quantifies circulating concentrations of the structural damage indicators S100b, and myelin basic protein (MBP), and the biomarkers of oxidative stress hydroxynonenal (HNE), malondialdehyde (MDA), carboxy-methyl-lysine (CML), and 8-hydroxy-2'-deoxy-guanosine (8-OHDG). Significant increases in circulating S100b, MBP, and HNE were observed in TBI patient samples compared to 8 uninjured controls, and there was a significant decrease in CML. This small exploratory study supports the current literature on S100b and MBP elevation in TBI, and reveals potential for the use of peripheral oxidative stress markers to assist in determination of TBI severity. Further investigation is required to validate results and confirm trends.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Estresse Oxidativo , Adulto , Aldeídos/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Proteína Básica da Mielina/sangue , Projetos Piloto , Estudos Prospectivos , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Resultado do Tratamento
6.
Anal Bioanal Chem ; 408(22): 6223-33, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27382971

RESUMO

Quantitative analysis of small molecules by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been a challenging task due to matrix-derived interferences in low m/z region and poor reproducibility of MS signal response. In this study, we developed an approach by applying black phosphorus (BP) as a matrix-assisted laser desorption ionization (MALDI) matrix for the quantitative analysis of small molecules for the first time. Black phosphorus-assisted laser desorption/ionization mass spectrometry (BP/ALDI-MS) showed clear background and exhibited superior detection sensitivity toward quaternary ammonium compounds compared to carbon-based materials. By combining stable isotope labeling (SIL) strategy with BP/ALDI-MS (SIL-BP/ALDI-MS), a variety of analytes labeled with quaternary ammonium group were sensitively detected. Moreover, the isotope-labeled forms of analytes also served as internal standards, which broadened the analyte coverage of BP/ALDI-MS and improved the reproducibility of MS signals. Based on these advantages, a reliable method for quantitative analysis of aldehydes from complex biological samples (saliva, urine, and serum) was successfully established. Good linearities were obtained for five aldehydes in the range of 0.1-20.0 µM with correlation coefficients (R (2)) larger than 0.9928. The LODs were found to be 20 to 100 nM. Reproducibility of the method was obtained with intra-day and inter-day relative standard deviations (RSDs) less than 10.4 %, and the recoveries in saliva samples ranged from 91.4 to 117.1 %. Taken together, the proposed SIL-BP/ALDI-MS strategy has proved to be a reliable tool for quantitative analysis of aldehydes from complex samples. Graphical Abstract An approach for the determination of small molecules was developed by using black phosphorus (BP) as a matrix-assisted laser desorption ionization (MALDI) matrix.


Assuntos
Aldeídos/sangue , Aldeídos/urina , Fósforo/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Aldeídos/análise , Humanos , Marcação por Isótopo/métodos , Limite de Detecção , Saliva/química
7.
Toxicol Appl Pharmacol ; 283(1): 65-74, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25585349

RESUMO

(-)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity.


Assuntos
Catequina/análogos & derivados , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Alanina Transaminase/sangue , Aldeídos/sangue , Animais , Aspartato Aminotransferases/sangue , Catalase/metabolismo , Catequina/administração & dosagem , Catequina/toxicidade , Glutationa Peroxidase/metabolismo , Histonas/metabolismo , Interleucina-6/sangue , Fígado/metabolismo , Masculino , Dose Máxima Tolerável , Camundongos , Fator 2 Relacionado a NF-E2/genética , Superóxido Dismutase/metabolismo , Chá/química , Tiorredoxina Redutase 1/genética , Tiorredoxina Redutase 1/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
8.
J Pharm Biomed Anal ; 105: 55-63, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25527982

RESUMO

Salicylaldehyde isonicotinoyl hydrazone (SIH) is an intracellular iron chelator with well documented potential to protect against oxidative injury both in vitro and in vivo. However, it suffers from short biological half-life caused by fast hydrolysis of the hydrazone bond. Recently, a concept of boronate prochelators has been introduced as a strategy that might overcome these limitations. This study presents two complementary analytical methods for detecting the prochelator-boronyl salicylaldehyde isonicotinoyl hydrazone-BSIH along with its active metal-binding chelator SIH in different solution matrices and concentration ranges. An LC-UV method for determination of BSIH and SIH in buffer and cell culture medium was validated over concentrations of 7-115 and 4-115 µM, respectively, and applied to BSIH activation experiments in vitro. An LC-MS assay was validated for quantification of BSIH and SIH in plasma over the concentration range of 0.06-23 and 0.24-23 µM, respectively, and applied to stability studies in plasma in vitro as well as analysis of plasma taken after i.v. administration of BSIH to rats. A Zorbax-RP bonus column and mobile phases containing either phosphate buffer with EDTA or ammonium formate and methanol/acetonitrile mixture provided suitable conditions for the LC-UV and LC-MS analysis, respectively. Samples were diluted or precipitated with methanol prior to analysis. These separative analytical techniques establish the first validated protocols to investigate BSIH activation by hydrogen peroxide in multiple matrices, directly compare the stabilities of the prochelator and its chelator in plasma, and provide the first basic pharmacokinetic data of this prochelator. Experiments reveal that BSIH is stable in all media tested and is partially converted to SIH by H2O2. The observed integrity of BSIH in plasma samples from the in vivo study suggests that the concept of prochelation might be a promising strategy for further development of aroylhydrazone cytoprotective agents.


Assuntos
Aldeídos/análise , Ácidos Borônicos/análise , Quelantes/análise , Cromatografia Líquida/métodos , Hidrazonas/análise , Ácidos Isonicotínicos/análise , Espectrometria de Massas/métodos , Espectrofotometria Ultravioleta/métodos , Aldeídos/sangue , Animais , Ácidos Borônicos/sangue , Meios de Cultura/química , Estabilidade de Medicamentos , Hidrazonas/sangue , Ácidos Isonicotínicos/sangue , Masculino , Estrutura Molecular , Ratos Wistar , Padrões de Referência , Sensibilidade e Especificidade
9.
PLoS One ; 9(7): e100591, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24984001

RESUMO

The mycotoxin deoxynivalenol (DON), one of the most common food contaminants, primarily targets the gastrointestinal tract to affect animal and human health. This study was conducted to examine the protective function of glutamic acid on intestinal injury and oxidative stress caused by DON in piglets. Twenty-eight piglets were assigned randomly into 4 dietary treatments (7 pigs/treatment): 1) uncontaminated control diet (NC), 2) NC+DON at 4 mg/kg (DON), 3) NC+2% glutamic acid (GLU), and 4) NC+2% glutamic acid + DON at 4 mg/kg (DG). At day 15, 30 and 37, blood samples were collected to determine serum concentrations of CAT (catalase), T-AOC (total antioxidant capacity), H2O2 (hydrogen peroxide), NO (nitric oxide), MDA (maleic dialdehyde), DAO (diamine oxidase) and D-lactate. Intestinal morphology, and the activation of Akt/mTOR/4EBP1 signal pathway, as well as the concentrations of H2O2, MDA, and DAO in kidney, liver and small intestine, were analyzed at day 37. Results showed that DON significantly (P<0.05) induced oxidative stress in piglets, while this stress was remarkably reduced with glutamic acid supplementation according to the change of oxidative parameters in blood and tissues. Meanwhile, DON caused obvious intestinal injury from microscopic observations and permeability indicators, which was alleviated by glutamic acid supplementation. Moreover, the inhibition of DON on Akt/mTOR/4EBP1 signal pathway was reduced by glutamic acid supplementation. Collectively, these data suggest that glutamic acid may be a useful nutritional regulator for DON-induced damage manifested as oxidative stress, intestinal injury and signaling inhibition.


Assuntos
Ácido Glutâmico/farmacologia , Enteropatias/sangue , Enteropatias/induzido quimicamente , Enteropatias/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Tricotecenos/toxicidade , Aldeídos/sangue , Amina Oxidase (contendo Cobre)/sangue , Animais , Antioxidantes/metabolismo , Catalase/sangue , Humanos , Peróxido de Hidrogênio/sangue , Ácido Láctico/sangue , Óxido Nítrico/sangue , Suínos
10.
Biochem Biophys Res Commun ; 443(3): 991-6, 2014 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-24361890

RESUMO

It has recently been reported that expression of heme oxygenase-1 (HO-1) plays a protective role against many diseases. Furthermore, n-3 polyunsaturated fatty acids (PUFAs) were shown to induce HO-1 expression in several cells in vitro, and in a few cases also in vivo. However, very few reports have demonstrated that n-3 PUFAs induce HO-1 in vivo. In this study, we examined the effect of fish-oil dietary supplementation on the distribution of fatty acids and their peroxidative metabolites and on the expression of HO-1 in multiple tissues (liver, kidney, heart, lung, spleen, intestine, skeletal muscle, white adipose, brown adipose, brain, aorta, and plasma) of C57BL/6 mice. Mice were divided into 4 groups, and fed a control, safflower-oil, and fish-oil diet for 3 weeks. One group was fed a fish-oil diet for just 1 week. The concentration of fatty acids, 4-hydroxy hexenal (4-HHE), and 4-hydroxy nonenal (4-HNE), and the expression of HO-1 mRNA were measured in the same tissues. We found that the concentration of 4-HHE (a product of n-3 PUFAs peroxidation) and expression of HO-1 mRNA were significantly increased after fish-oil treatment in most tissues. In addition, these increases were paralleled by an increase in the level of docosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) in each tissue. These results are consistent with our previous results showing that DHA induces HO-1 expression through 4-HHE in vascular endothelial cells. In conclusion, we hypothesize that the HO-1-mediated protective effect of the fish oil diet may be through production of 4-HHE from DHA but not EPA in various tissues.


Assuntos
Aldeídos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Heme Oxigenase-1/biossíntese , Especificidade de Órgãos , Aldeídos/sangue , Animais , Ácido Araquidônico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Indução Enzimática , Ácidos Graxos Ômega-3/sangue , Heme Oxigenase-1/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
11.
J Cyst Fibros ; 12(1): 35-41, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22781546

RESUMO

UNLABELLED: Oxidative stress plays an important role in cystic fibrosis (CF). However, there is a lack of validated biomarkers of oxidative damage that correlate with the antioxidant needs of patients with CF. OBJECTIVE: To investigate oxidative stress in stable pediatric CF patients and evaluate if vitamin supplementation may be tailored to individual needs and oxidative status. RESULTS: Lipid-adducts 4-hydroxynonenal (HNE-L) and malonaldehyde (MDA-L) (chromolipids) were elevated in the majority of patients despite normal plasma vitamin E, A and C. HNE-L and MDA-L increased with age, while plasma vitamins decreased. The most relevant correlation was identified between vitamin C and chromolipids. Patients with pancreatic insufficiency (PI) showed significantly higher plasma chromolipids despite no differences in plasma vitamins. CONCLUSIONS: The majority of patients showed elevated plasma chromolipids that increased with age. Antioxidant vitamin reference ranges provide incomplete information on the redox status. CF patients with PI showed excessive oxidative stress damage.


Assuntos
Aldeídos/sangue , Inibidores de Cisteína Proteinase/sangue , Fibrose Cística/metabolismo , Malondialdeído/sangue , Estresse Oxidativo/fisiologia , Biomarcadores/sangue , Criança , Pré-Escolar , Fibrose Cística/sangue , Insuficiência Pancreática Exócrina/sangue , Feminino , Fluorometria , Humanos , Lactente , Masculino , Valores de Referência
12.
J Neurosurg Spine ; 17(2): 134-40, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22735048

RESUMO

OBJECT: The pathogenesis of cervical spondylotic myelopathy (CSM) is related to both primary mechanical and secondary biological injury. The authors of this study explored a novel, noninvasive method of promoting neuroprotection in myelopathy by using curcumin to minimize oxidative cellular injury and the capacity of omega-3 fatty acids to support membrane structure and improve neurotransmission. METHODS: An animal model of CSM was created using a nonresorbable expandable polymer placed in the thoracic epidural space, which induced delayed myelopathy. Animals that underwent placement of the expandable polymer were exposed to either a diet rich in docosahexaenoic acid and curcumin (DHA-Cur) or a standard Western diet (WD). Twenty-seven animals underwent serial gait testing, and spinal cord molecular assessments were performed after the 6-week study period. RESULTS: At the conclusion of the study period, gait analysis revealed significantly worse function in the WD group than in the DHA-Cur group. Levels of brain-derived neurotrophic factor (BDNF), syntaxin-3, and 4-hydroxynonenal (4-HNE) were measured in the thoracic region affected by compression and lumbar enlargement. Results showed that BDNF levels in the DHA-Cur group were not significantly different from those in the intact animals but were significantly greater than in the WD group. Significantly higher lumbar enlargement syntaxin-3 in the DHA-Cur animals combined with a reduction in lipid peroxidation (4-HNE) indicated a possible healing effect on the plasma membrane. CONCLUSIONS: Data in this study demonstrated that DHA-Cur can promote spinal cord neuroprotection and neutralize the clinical and biochemical effects of myelopathy.


Assuntos
Curcuma/metabolismo , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Aldeídos/sangue , Animais , Fator Neurotrófico Derivado do Encéfalo/sangue , Doença Crônica , Curcuma/efeitos dos fármacos , Dieta/métodos , Ácidos Docosa-Hexaenoicos/farmacologia , Masculino , Fármacos Neuroprotetores/farmacologia , Proteínas Qa-SNARE/sangue , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/etiologia
13.
Inflammation ; 35(3): 913-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21976127

RESUMO

The purpose of the present study was to investigate the antibacterial and anti-inflammatory activity of Angelica sinensis extract (AE), Sophora flavescens extract (SE), and herb pair A. sinensis and S. flavescens extract (HPE). Endotoxin-induced uveitis (EIU) was induced in rats by a footpad injection of lipopolysaccharide. The anti-inflammatory potential of AE, SE, and HPE in the regulation of nuclear factor kappa B (NF-κB), maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), adhesion molecule (ICAM-1), and cyclooxygenase-2 (COX-2) was determined by ELISA and immunohistochemistry. HPE showed strong antibacterial activity at all tested concentrations (1.25, 2.5, and 5 µg/ml) to Escherichia coli, Staphylococcus aureus, and Shigella Castellani and Chalmers. HPE significantly inhibited EIU-induced upregulation of NF-κB activation and the production of IL-1ß, TNF-α, iNOS, ICAM-1, and COX-2. Moreover, HPE suppressed MDA and infiltration of PMN. The study supports the hypothesis that the antipimple and anti-eczema activities of Dangguikushen compound recipe are attributed to herb pairs, A. sinensis and S. flavescens, used in combination.


Assuntos
Angelica sinensis , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sophora , Uveíte/tratamento farmacológico , Aldeídos/sangue , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Combinação de Medicamentos , Escherichia coli/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/imunologia , Masculino , Testes de Sensibilidade Microbiana , NF-kappa B/metabolismo , Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Shigella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Uveíte/induzido quimicamente
14.
Br J Nutr ; 108(2): 315-26, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22136711

RESUMO

Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18-50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g/d of fish oil (1.6 g/d EPA+DHA; n 17), 8 g/d of oxidised fish oil (1.6 g/d EPA+DHA; n 18) or 8 g/d of high-oleic sunflower oil (n 19). Fasting blood and morning spot urine samples were collected at weeks 0, 3 and 7. No significant changes between the different groups were observed with regard to urinary 8-iso-PGF2α; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and α-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA+DHA was observed in both fish oil groups, but no significant difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short-term effects in healthy human subjects.


Assuntos
Óleo de Fígado de Bacalhau/efeitos adversos , Óleo de Fígado de Bacalhau/química , Suplementos Nutricionais/efeitos adversos , Suplementos Nutricionais/análise , Estresse Oxidativo , Adulto , Aldeídos/sangue , Biomarcadores/sangue , Biomarcadores/urina , Proteína C-Reativa/análise , Dinoprosta/análogos & derivados , Dinoprosta/urina , Método Duplo-Cego , Eritrócitos/enzimologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Peroxidação de Lipídeos , Masculino , Noruega , Oxirredução , Oxirredutases/sangue , Pacientes Desistentes do Tratamento , Adulto Jovem , alfa-Tocoferol/sangue
15.
J Toxicol Sci ; 36(6): 797-809, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22129743

RESUMO

Recently, we identified that olive leaf extract (OLE) prevents lead (Pb)-induced abnormalities in behavior and neurotransmitters production in chronic Pb exposure in rats. The aim of the present study was to provide additional evidence that OLE acts as an anti-apoptotic, anti-inflammatory, and antioxidant mediator in Pb exposed rats. 4-weeks old Wistar rats were exposed or not to 250 mg/l Pb for 13-weeks and then exposed to tap water containing or not 0.1% OLE for additional 2-weeks. Atomic absorption spectrophotometry showed significantly elevated Pb levels in the hippocampus and serum and reaches 5 and 42 µg/mg tissue, respectively. In the hippocampus, the examination of markers of apoptosis and inflammation revealed an increase in caspase-3 activity and DNA fragmentation as well as tumor necrosis factor alpha, interleukin-1 beta and prostaglandin E2 in Pb-exposed rats. In addition, our findings showed that Pb induced 4-hydroxynonenal production and inhibited antioxidant-related enzyme activity, such as glutathione-S-transferase as wells as energy metabolism-related enzyme activity, such as NADP-isocitrate dehydrogenase and glucose transporter. Upon examination of signaling pathways involved in apoptosis process, we found that Pb induced p38 mitogen activated protein kinase (MAPK) and Akt phosphorylation, but in contrast, inhibited that of ERK(1/2). Interestingly, OLE administration diminished tissue Pb deposition and prevented all Pb effects. In the frontal cortex, our data also showed that OLE-abolished Pb-induced caspase-3 activity and DNA fragmentation. Collectively, these data support the use of OLE by traditional medicine to counter Pb neurotoxicity.


Assuntos
Inflamação/tratamento farmacológico , Chumbo/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Olea/química , Extratos Vegetais/uso terapêutico , Aldeídos/sangue , Animais , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Caspase 3/metabolismo , Fragmentação do DNA , Dinoprostona/metabolismo , Glutationa Transferase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Isocitrato Desidrogenase/metabolismo , Chumbo/sangue , Chumbo/farmacocinética , Masculino , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
16.
J Med Food ; 14(11): 1370-4, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21942497

RESUMO

This study was designed to investigate if α-mangostin (α-M), a xanthone present in the pericarp of Garcinia mangostana L., was able to protect against reperfusion injury in Langendorff-reperfused hearts. It was observed that α-M maintains the cardiac mechanical work, diminishes the area of infarct, and prevents the decrease in cardiac ATP and phosphocreatine levels in the reperfused myocardium. The protective effect of this xanthone was associated with reduction of oxidative stress. α-M treatment prevented reperfusion injury-induced protein oxidation (protein carbonyl content), lipid peroxidation (malondialdehyde and 4-hydroxynonenal content), and diminution of glutathione content. In fact, after α-M treatment, the values in these parameters were comparable to those obtained in nonreperfused hearts. In summary, α-M induces a protective effect in postischemic heart associated to the prevention of oxidative stress secondary to reperfusion injury.


Assuntos
Garcinia mangostana/química , Coração/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Xantonas/farmacologia , Aldeídos/sangue , Animais , Antioxidantes/farmacologia , Glutationa/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Miocárdio/química , Fosfocreatina/sangue , Fosfocreatina/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo
17.
J Am Coll Nutr ; 29(1): 31-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20595643

RESUMO

OBJECTIVE: To compare the effects of supplementation of green tea beverage or green tea extracts with controls on body weight, glucose and lipid profile, biomarkers of oxidative stress, and safety parameters in obese subjects with metabolic syndrome. DESIGN: Randomized, controlled prospective trial. SETTING: General Clinical Research Center (GCRC) at University of Oklahoma Health Sciences Center (OUHSC). SUBJECTS: Thirty-five subjects with obesity and metabolic syndrome were recruited in age- and gender-matched trios and were randomly assigned to the control (4 cups water/d), green tea (4 cups/d), or green tea extract (2 capsules and 4 cups water/d) group for 8 weeks. The tea and extract groups had similar dosing of epiogallocatechin-3-gallate (EGCG), the active compound in green tea. METHODS: Anthropometrics, blood pressure, fasting glucose and lipids, nuclear magnetic resonance (NMR)-based lipid particle size, safety parameters, biomarkers of oxidative stress (oxidized low-density lipoprotein [LDL], myeloperoxidase [MPO], malondialdehyde and hydroxynonenals [MDA and HNE]), and free catechins were analyzed at screen and at 4 and 8 weeks of the study. RESULTS: Pairwise comparisons showed green tea beverage and green tea extracts caused a significant decrease in body weight and body mass index (BMI) versus controls at 8 weeks (-2.5 +/- 0.7 kg, p < 0.01, and -1.9 +/- 0.6, p < 0.05, respectively). Green tea beverage showed a decreasing trend in LDL-cholesterol and LDL/high-density lipoprotein (HDL) versus controls (p < 0.1). Green tea beverage also significantly decreased MDA and HNE (-0.39 +/- 0.06 microM, p < 0.0001) versus controls. Plasma free catechins were detectable in both beverage and extract groups versus controls at screen and at 8 weeks, indicating compliance and bioavailability of green tea catechins. CONCLUSIONS: Green tea beverage consumption (4 cups/d) or extract supplementation (2 capsules/d) for 8 weeks significantly decreased body weight and BMI. Green tea beverage further lowered lipid peroxidation versus age- and gender-matched controls, suggesting the role of green tea flavonoids in improving features of metabolic syndrome in obese patients.


Assuntos
Peso Corporal/efeitos dos fármacos , Camellia sinensis/química , Colesterol/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adulto , Aldeídos/sangue , Disponibilidade Biológica , Índice de Massa Corporal , Estudos de Casos e Controles , Catequina/análogos & derivados , Catequina/sangue , Catequina/farmacologia , Catequina/uso terapêutico , Feminino , Humanos , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Masculino , Malondialdeído/sangue , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Cooperação do Paciente , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Método Simples-Cego
18.
Clin Nephrol ; 73(3): 210-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20178720

RESUMO

UNLABELLED: Recombinant human erythropoetin beta; (rHuEPO) has not only an erythropoietic effect but also appears to affect production of cytokines and may improve nutritional status of dialysis patients. Darbepoetin alpha; is a new erythropoiesis-stimulating protein with a threefold longer serum half-life when compared with rHuEPO. The objective of this prospective study was to assess oxidative stress, inflammation, nutrition and hematological response in peritoneal dialysis (PD) patients who were switched from rHuEPO beta to darbepoetin alpha. 12 stable PD patients (6 M, 6 F; mean age 56.2 +/- 15.1 yr.) were evaluated during this study together with 22 healthy volunteers serving as a control group. All patients had been receiving erythropoetin beta subcutaneously once a week before they were reassigned to darbepoetin. The new drug was administered every other week for 6 months, in a dose equivalent to a weekly dose of previously taken rHuEPO. Hematology, iron status and biochemical profiles were evaluated monthly. Markers of oxidative stress: malondialdehyde/ 4-hydroxynoneal (MDA/4HNE), carbonyl groups (CG), oxyLDL and AGEs and markers of inflammation: CRP, TNF alpha, IL-6 were measured on rHuEPO beta before the switch to darbepoetin, and after 1st and 6th month of darbepoetin treatment. The assessment of nutritional status was determined by body mass index (BMI), serum albumin concentration and Subjective Global Assessment (SGA). RESULTS: Mean levels of Hb and Hct were stable during 6 months of observation and not significantly different from the data observed for on rHuEPO. Nutritional status was good in 9 patients, 3 patients were malnourished at the beginning of this study as assessed by SGA and this status persisted to the end of observation. The levels of markers of oxidative stress and inflammation were statistically higher than in the control group (p < 0.05). CONCLUSION: Darbepoetin alpha given subcutaneously once every 2 weeks is effective for the treatment of anemia in PD patients. Less frequent administration of darbepoetin has a biological response similar to weekly administration of rHuEPO.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/análogos & derivados , Inflamação/diagnóstico , Falência Renal Crônica/terapia , Estado Nutricional/fisiologia , Estresse Oxidativo/fisiologia , Diálise Peritoneal , Adulto , Aldeídos/sangue , Anemia/sangue , Anemia/etiologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Darbepoetina alfa , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Feminino , Seguimentos , Hematínicos/administração & dosagem , Hematínicos/uso terapêutico , Humanos , Inflamação/sangue , Inflamação/complicações , Injeções Subcutâneas , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Proteínas Recombinantes , Albumina Sérica/metabolismo , Fatores de Tempo , Resultado do Tratamento
19.
Zhong Yao Cai ; 33(9): 1428-33, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21243773

RESUMO

OBJECTIVE: To study metabolic rule in rats for heartleaf houttuynia herb injection and Sodium New Houttuyfonate injection. METHODS: The GC-MS was used to determine metabolites in plasma and urine of rats after intravenous and oral administration of heartleaf houttuynia herb injection as multi-component and Sodium New Houttuyfonate injection as single component. RESULTS: For rats 8 common metabolites were determined in plasma after intravenous administration of heartleaf houttuynia herb injection and Sodium New Houttuyfonate injection, meanwhile 39 in urine. The 16 common metabolites were determined in plasma after oral administration, and 12 in urine. The 9 and 11 of same metabolites were determined in plasma and urine respectively after intravenous and oral administration of heartleaf houttuynia herb injection, 8 and 17 common metabolites for Sodium New Houttuyfonate injection. CONCLUSION: The metabolites of heartleaf houttuynia herb and Sodium New Houttuyfonate injection in rats are the same or similar after intravenous and oral administration, and there are the same structure types between metabolites and original constituents of preparations. The metabolic pathways of the two preparations in rats are the same. There is metabolic Network Compatibility in organism between multi-components, single components and different administration forms for traditional Chinese medicine.


Assuntos
Aldeídos/metabolismo , Anti-Inflamatórios não Esteroides/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Saururaceae/química , Administração Oral , Aldeídos/administração & dosagem , Aldeídos/sangue , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Infusões Intravenosas , Masculino , Redes e Vias Metabólicas , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
20.
J Am Coll Nutr ; 27(2): 267-73, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18689558

RESUMO

OBJECTIVE: While tomato product supplementation, containing antioxidant carotenoids, including lycopene, decreases oxidative stress, the role of purified lycopene as an antioxidant remains unclear. Thus, we tested the effects of different doses of purified lycopene supplementation on biomarkers of oxidative stress in healthy volunteers. METHODS: This was a double-blind, randomized, placebo-controlled trial, examining the effects of 8-week supplementation of purified lycopene, on plasma lycopene levels, biomarkers of lipid peroxidation {LDL oxidizability, malondialdehyde & hydroxynonenals (MDA & HNE), urinary F(2)-isoprostanes}, and markers of DNA damage in urine and lymphocytes. Healthy adults (n = 77, age > or = 40 years), consumed a lycopene-restricted diet for 2 weeks, and were then randomized to receive 0, 6.5, 15, or 30 mg lycopene/day for 8 weeks, while on the lycopene-restricted diet. Blood and urine samples were collected at the beginning and end of Week 2 of lycopene-restricted diet, and at end of Week 10 of the study. RESULTS: Independent of the dose, plasma lycopene levels significantly increased in all lycopene supplemented groups versus placebo (p < 0.05). ANOVA revealed a significant decrease in DNA damage by the comet assay (p = 0.007), and a significant decrease in urinary 8-hydroxy deoxoguanosine (8-OHdG) at 8 weeks versus baseline (p = 0.0002), with 30 mg lycopene/day. No significant inter- or intra-group differences were noted for glucose, lipid profile, or other biomarkers of lipid peroxidation at any dose/time point. CONCLUSIONS: Thus, purified lycopene was bioavailable and was shown to decrease DNA oxidative damage and urinary 8-OHdG at the high dose.


Assuntos
Antioxidantes/administração & dosagem , Carotenoides/administração & dosagem , Carotenoides/sangue , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Aldeídos/sangue , Biomarcadores/metabolismo , Glicemia/metabolismo , Ensaio Cometa , DNA/efeitos dos fármacos , DNA/metabolismo , Dano ao DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , F2-Isoprostanos/urina , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/sangue , Licopeno , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia
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