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1.
PLoS One ; 15(12): e0243755, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33320868

RESUMO

There have been recent calls for strategies to improve oral health in athletes. High carbohydrate diets, exercise induced dehydration and transient perturbations to immune function combine to increase oral disease risk in this group. We tested whether a single dose of nitrate (NO3-) would offset the reduction in salivary pH following carbohydrate ingestion before and after an exercise bout designed to cause mild dehydration. Eleven trained male runners ([Formula: see text] 53 ± 9 ml∙kg-1∙min-1, age 30 ± 7 years) completed a randomised placebo-controlled study comprising four experimental trials. Participants ingested the following fluids one hour before each trial: (a) 140 ml of water (negative-control), (b) 140 ml of water (positive-control), (c) 140 ml of NO3- rich beetroot juice (~12.4 mmol NO3-) (NO3- trial) or (d) 140 ml NO3- depleted beetroot juice (placebo-trial). During the negative-control trial, participants ingested 795 ml of water in three equal aliquots: before, during, and after 90 min of submaximal running. In the other trials they received 795 ml of carbohydrate supplements in the same fashion. Venous blood was collected before and after the exercise bout and saliva was sampled before and repeatedly over the 20 min following carbohydrate or water ingestion. As expected, nitrite (NO2-) and NO3- were higher in plasma and saliva during the NO3- trial than all other trials (all P<0.001). Compared to the negative-control, salivary-pH was significantly reduced following the ingestion of carbohydrate in the positive-control and placebo trials (both P <0.05). Salivary-pH was similar between the negative-control and NO3- trials before and after exercise despite ingestion of carbohydrate in the NO3- trial (both P≥0.221). Ingesting NO3- attenuates the expected reduction in salivary-pH following carbohydrate supplements and exercise-induced dehydration. NO3- should be considered by athletes as a novel nutritional strategy to reduce the risk of developing acidity related oral health conditions.


Assuntos
Beta vulgaris/química , Carboidratos da Dieta/farmacologia , Sucos de Frutas e Vegetais/análise , Nitritos/análise , Resistência Física , Corrida/fisiologia , Saliva/efeitos dos fármacos , Adulto , Suplementos Nutricionais/análise , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Masculino , Nitratos/sangue , Nitritos/sangue , Saliva/química
2.
J Stroke Cerebrovasc Dis ; 29(9): 104830, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807407

RESUMO

BACKGROUND AND PURPOSE: Nitric oxide (NO) plays a key role in ischemia and shows potential as a biomarker for ischemia. We measured mixed venous nitrite (NO2-) as a proxy for NO, during controlled cerebral ischemia in patients with moyamoya disease (MMD) during direct extracranial/intracranial (EC/IC) bypass surgery with temporary occlusion of the M4 branch of the middle cerebral artery (MCA) to permit anastomosis with the superficial temporal artery (STA). This small, focal ischemic event is not reliably detected using cerebral oximetry, somatosensory evoked potentials (SSEPs) or electroencephalography (EEG). METHODS: We enrolled nine adult MMD patients (n=8 female, n=1 male) undergoing direct EC/IC bypass surgery. Nitrite was measured at least one hour prior to MCA occlusion, and before, during and after anastomosis. Cortical function was monitored using either multi-lead EEG and SSEPs, or frontal EEG activity. RESULTS: Mixed venous NO2- was significantly elevated (p<0.05) within 12 min following arterial occlusion vs. baseline. An M4 branch of the MCA was cross clamped for a median duration of 18 (IQR = 5) minutes during anastomosis. One patient with elevated NO2- showed a transient neurologic deficit that resolved 3 days post-operatively. CONCLUSIONS: Mixed venous NO2- was significantly elevated shortly following cerebral artery occlusion vs. baseline in a majority of the study subjects, suggesting that NO2- is a potential biomarker for ischemia. Since all patients received identical burst suppression anesthesia and vasopressors, the fact that NO2- was not elevated during cross-clamp in all patients supports the conclusion that the NO2- elevation is likely due to ischemia.


Assuntos
Isquemia Encefálica/diagnóstico , Revascularização Cerebral , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/cirurgia , Nitritos/sangue , Artérias Temporais/cirurgia , Oclusão Terapêutica , Adulto , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Revascularização Cerebral/efeitos adversos , Circulação Cerebrovascular , Circulação Colateral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Doença de Moyamoya/sangue , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/fisiopatologia , Oclusão Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Vasodilatação
3.
Nitric Oxide ; 103: 29-30, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32712272

RESUMO

Most outcomes of COVID-19 are associated with dysfunction of the vascular system, particularly in the lung. Inhalation of nitric oxide (NO) gas is currently being investigated as a treatment for patients with moderate to severe COVID-19. In addition to the expected vasodilation effect, it has been also suggested that NO potentially prevents infection by SARS-CoV-2. Since NO is an unstable radical molecule that is easily oxidized by multiple mechanisms in the human body, it is practically difficult to control its concentration at lesions that need NO. Inorganic nitrate and/or nitrite are known as precursors of NO that can be produced through chemical as well enzymatic reduction. It appears that this NO synthase (NOS)-independent mechanism has been overlooked in the current developing of clinical treatments. Here, I suggest the missing link between nitrate and COVID-19 in terms of hypoxic NO generation.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Pneumonia Viral/tratamento farmacológico , Antivirais/metabolismo , Ácido Ascórbico/química , Ácido Ascórbico/uso terapêutico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/prevenção & controle , Fatores Relaxantes Dependentes do Endotélio/metabolismo , Humanos , Nitratos/sangue , Nitritos/sangue , Nitritos/química , Pandemias/prevenção & controle , Pneumonia Viral/metabolismo , Pneumonia Viral/prevenção & controle , Vasodilatação/efeitos dos fármacos
4.
PLoS One ; 15(6): e0235047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574223

RESUMO

PURPOSE: Nitrate (NO3-), through its conversion to nitrite (NO2-) and nitric oxide, has been shown to increase exercise tolerance in healthy younger adults and older diseased patients. Nitrate's effect in well-trained middle to older-aged adults has not been studied. Therefore, the purpose of this investigation was to examine the effects of a NO3- rich beverage on submaximal constant work rate exercise time in well-trained middle to older-aged adults. METHODS: This was a randomized controlled cross-over trial with 15 well-trained middle to older-aged adults, 41-64 year-old, who received one of two treatments (NO3- rich beverage then placebo or placebo then NO3- rich beverage), after which an exercise test at 75 percent of the subject's maximal work rate was completed. RESULTS: The NO3- rich beverage increased plasma NO3- and NO2- levels by 260 µM and 0.47 µM, respectively (p<0.001). Exercise time was not significantly different (p = 0.31) between the NO3- rich versus placebo conditions (1130±151 vs 1060±132 sec, respectively). Changes in exercise time between the two conditions ranged from a 55% improvement to a 40% decrease with the NO3- rich beverage. Oxygen consumption and rating of perceived exertion were not significantly different between the two conditions. CONCLUSION: In middle to older-aged well-trained adults, NO3- supplementation has non-significant, albeit highly variable, effects on exercise tolerance. ClinicalTrials.gov Identifier: NCT03371966.


Assuntos
Bebidas , Suplementos Nutricionais , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Nitratos/administração & dosagem , Adulto , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Teste de Esforço , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/sangue , Nitritos/sangue , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Consumo de Oxigênio/fisiologia
5.
PLoS One ; 15(4): e0230551, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32255785

RESUMO

OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.


Assuntos
Interleucina-10/metabolismo , Terapia com Luz de Baixa Intensidade , Esclerose Múltipla Recidivante-Remitente/radioterapia , Nitritos/metabolismo , Adulto , Feminino , Humanos , Lasers Semicondutores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/patologia , Nitritos/sangue , Modalidades de Fisioterapia , Artéria Radial/metabolismo , Artéria Radial/efeitos da radiação , Adulto Jovem
6.
Nitric Oxide ; 99: 25-33, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32272260

RESUMO

We tested the hypothesis that acute supplementation with nitrate (NO3-)-rich beetroot juice (BR) would improve quadriceps muscle oxygenation, pulmonary oxygen uptake (V˙O2) kinetics and exercise tolerance (Tlim) in normoxia and that these improvements would be augmented in hypoxia and attenuated in hyperoxia. In a randomised, double-blind, cross-over study, ten healthy males completed two-step cycle tests to Tlim following acute consumption of 210 mL BR (18.6 mmol NO3-) or NO3--depleted beetroot juice placebo (PL; 0.12 mmol NO3-). These tests were completed in normobaric normoxia [fraction of inspired oxygen (FIO2): 21%], hypoxia (FIO2: 15%) and hyperoxia (FIO2: 40%). Pulmonary V˙O2 and quadriceps tissue oxygenation index (TOI), derived from multi-channel near-infrared spectroscopy, were measured during all trials. Plasma [nitrite] was higher in all BR compared to all PL trials (P < 0.05). Quadriceps TOI was higher in normoxia compared to hypoxia (P < 0.05) and higher in hyperoxia compared to hypoxia and normoxia (P < 0.05). Tlim was improved after BR compared to PL ingestion in the hypoxic trials (250 ± 44 vs. 231 ± 41 s; P = 0.006; d = 1.13), with the magnitude of improvement being negatively correlated with quadriceps TOI at Tlim (r = -0.78; P < 0.05). Tlim was not improved following BR ingestion in normoxia (BR: 364 ± 98 vs. PL: 344 ± 78 s; P = 0.087, d = 0.61) or hyperoxia (BR: 492 ± 212 vs. PL: 472 ± 196 s; P = 0.273, d = 0.37). BR ingestion increased peak V˙O2 in hypoxia (P < 0.05), but not normoxia or hyperoxia (P > 0.05). These findings indicate that BR supplementation is more likely to improve Tlim and peak V˙O2 in situations when skeletal muscle is more hypoxic.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Sucos de Frutas e Vegetais , Nitratos/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Oxigênio/metabolismo , Músculo Quadríceps/metabolismo , Administração Oral , Adulto , Beta vulgaris/química , Estudos Cross-Over , Método Duplo-Cego , Humanos , Hipóxia/prevenção & controle , Cinética , Masculino , Nitratos/administração & dosagem , Nitritos/sangue , Músculo Quadríceps/efeitos dos fármacos , Adulto Jovem
7.
Mol Cell Biochem ; 468(1-2): 47-58, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32162053

RESUMO

Patients with metabolic syndrome (MetS) often exhibit generalized endothelial and cardiac dysfunction with decreased nitric oxide (NO) production and/or bioavailability. Since phosphodiesterase 5 (PDE5) inhibitors restore NO signaling, we hypothesized that chronic treatment with long-acting PDE5 inhibitor tadalafil may enhance plasma NO levels and reduce cardiac dysfunction following ischemia/reperfusion (I/R) injury in C57BL/6NCrl-Leprdb-lb/Crl mice with MetS phenotypes. Adult male MetS mice were randomized to receive vehicle solvent or tadalafil (1 mg/kg,i.p.) daily for 28 days and C57BL/6NCrl mice served as healthy wild-type controls. After 28 days, cardiac function was assessed by echocardiography and hearts from a subset of mice were isolated and subjected to 30 min of global ischemia followed by 60 min of reperfusion (I/R) in ex vivo Langendorff mode. Body weight, blood lipids, and glucose levels were elevated in MetS mice as compared with wild-type controls. The dyslipidemia in MetS was ameliorated following tadalafil treatment. Although left ventricular (LV) systolic function was minimally altered in the MetS mice, there was a significant diastolic dysfunction as indicated by reduction in the ratio of peak velocity of early to late filling of the mitral inflow, which was significantly improved by tadalafil treatment. Post-ischemic cardiac function, heart rate, and coronary flow decreased significantly in MetS mice compared to wild-type controls, but preserved by tadalafil treatment. Myocardial infarct size was significantly smaller following I/R, which was associated with higher plasma levels of nitrate and nitrite in the tadalafil-treated MetS mice. In conclusion, tadalafil induces significant cardioprotective effects as shown by improvement of LV diastolic function, lipid profile, and reduced infarct size following I/R. Tadalafil treatment enhanced NO production, which may have contributed to the cardioprotective effects.


Assuntos
Síndrome Metabólica/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Óxido Nítrico/metabolismo , Inibidores da Fosfodiesterase 5/farmacologia , Tadalafila/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Cardiotônicos/farmacologia , Modelos Animais de Doenças , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Coração/efeitos dos fármacos , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Nitratos/sangue , Nitritos/sangue
8.
Ann Vasc Surg ; 62: 412-419, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31449936

RESUMO

BACKGROUND: Local and remote ischemic preconditioning has been used as a protective intervention against ischemia/reperfusion (I/R) damage in several preclinical and clinical studies. However, its physiological mechanisms are not completely known. I/R increases the production of reactive oxygen species, which also serve as messengers for a variety of functions. Hypoxia-inducible factor 1 alpha (HIF-1α) is probably the most important transcription factor mediator of hypoxic signaling. OBJECTIVE: We hypothesized that limb ischemic conditioning (LIC) induces a local oxidative/nitrosative stress and a correlated increase of HIF-1α plasma levels. METHODS: An observational, prospective, and single-center study has been conducted in 27 healthy volunteers. LIC was applied: three cycles (5 min of ischemia followed by 5 min of reperfusion) using an ischemia cuff placed on the upper left arm. Time course of 8-isoprostane, nitrite, and HIF-1α levels was measured in blood plasma. Venous blood was sampled from the left arm before tourniquet inflation (basal) and after LIC: 1 min and 2 hr for 8-isoprostane and nitrite; and 1 min, 2 hr, 8 hr, 24 hr, and 48 hr for HIF-1α. RESULTS: After LIC, we have found an early increase of 8-isoprostane and nitrite. HIF-1α increased at 2 and 8 hr after LIC. We found a direct correlation between HIF-1α and 8-isoprostane and nitrite plasma levels. CONCLUSIONS: We concluded that LIC induces an early oxidative/nitrosative stress in the arm followed by an increase of HIF-1α plasma levels correlated with 8-isoprostane and nitrite levels, possibly as a local response.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Precondicionamento Isquêmico/métodos , Estresse Oxidativo , Oclusão Terapêutica , Extremidade Superior/irrigação sanguínea , Adulto , Biomarcadores/sangue , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Feminino , Voluntários Saudáveis , Humanos , Masculino , Nitritos/sangue , Estresse Nitrosativo , Estudos Prospectivos , Fluxo Sanguíneo Regional , Espanha , Fatores de Tempo , Regulação para Cima , Adulto Jovem
9.
Inflammation ; 43(1): 155-167, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31654297

RESUMO

Systemic inflammatory response and generation of oxidative stress are known to contribute to scorpion venom-induced tissue damage. TLR receptors might represent a link between oxidative stress and inflammation; we therefore investigated whether or not TLR4 is involved in venom-induced immunopathology. The obtained results showed that pharmacological targeting of TLR4 with the selective inhibitor TAK-242 (Resatorvid) prevents the inflammatory response induced by subcutaneous administration of Androctonus australis hector (Aah) venom, as revealed by a significant decrease of neutrophil cell count in peripheral blood associated with significant decline of neutrophil degranulation and sequestration to the lung, liver, and kidney tissues. Moreover, TAK-242 administration inhibited nitrite levels increase in serum, malondialdehyde (MDA), and protein carbonyl tissue contents concomitantly with a significant increase of catalase activity and reduced glutathione (GSH) level in tissue homogenates. Furthermore, venom-induced increases in serum levels of organ dysfunction markers (lactate deshydrogenase, aminotransferase ALT and AST, creatinine and urea) were also significantly suppressed by pre-treatment with TLR4 inhibitor, concordantly with a remarkable improvement in the histological features in lung and liver tissues. The results of the present study indicate the potential role of TLR4 in venom-induced immunopathology and show the in vivo requirement of TLR4 signaling in mediating venom-induced tissue damage.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Neutrófilos/imunologia , Venenos de Escorpião/toxicidade , Sulfonamidas/farmacologia , Receptor 4 Toll-Like/imunologia , Animais , Catalase/metabolismo , Degranulação Celular/efeitos dos fármacos , Glutationa/análise , Inflamação/imunologia , Inflamação/patologia , Malondialdeído/análise , Camundongos , Neutrófilos/efeitos dos fármacos , Nitritos/sangue , Estresse Oxidativo/imunologia , Carbonilação Proteica/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/antagonistas & inibidores
10.
Biochem Pharmacol ; 173: 113754, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31837311

RESUMO

This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.71 ± 0.38 (25% IQR) and 4.76 (75% IQR) µM, p < 0.05). This was followed by a placebo-controlled, healthy volunteer study, which showed no effects on plasma nitrite. It was confirmed that different batches of extract had been used in the healthy volunteer studies, and this second batch lacked bioactivity, assessed using the in vitro model. No difference in plasma catechin levels was seen at 8 h following supplementation between the studies (252 ± 194 nM versus 50 ± 64 nM, p > 0.05), however HPLC-UV fingerprinting showed that the new batch had a 5-15% in major constituents (including procyanidins A2, B1 and B2) compared to the original batch. This research describes a robust mechanism for screening bioactive extracts for vascular effects. It also highlights batch variability as a significant limitation when using complex extracts for pharmacological activity, and suggests the use of in vitro systems as a tool to identify this problem in future studies.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Pinus/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Adolescente , Adulto , Catequina/análise , Catequina/sangue , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Voluntários Saudáveis , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/sangue , Óxido Nítrico/metabolismo , Nitritos/sangue , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Polifenóis/administração & dosagem , Polifenóis/isolamento & purificação , Adulto Jovem
11.
Br J Nutr ; 123(2): 135-148, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31647043

RESUMO

Oral arginine supplements are popular mainly for their presumed vasodilatory benefit. Arginine is a substrate for at least four enzymes including nitric oxide synthase (NOS) and arginase, but the impact of oral supplements on its different metabolic pathways is not clear. Deficiencies of arginine-metabolising enzymes are associated with conditions such as hyperammonaemia, endothelial dysfunction, central nervous system and muscle dysfunction, which complicate the use of oral arginine supplements. We examined the effect of l-arginine (l-Arg) and d-arginine (d-Arg), each at 500 mg/kg per d in drinking water administered for 4 weeks to separate groups of 9-week-old male Sprague-Dawley rats. We quantified the expression of enzymes and plasma, urine and organ levels of various metabolites of arginine. l-Arg significantly decreased cationic transporter-1 expression in the liver and the ileum and increased endothelial NOS expression in the aorta and the kidney and plasma nitrite levels, but did not affect the mean arterial pressure. l-Arg also decreased the expression of arginase II in the ileum, arginine:glycine amidinotransferase in the liver and the kidney and glyoxalase I in the liver, ileum and brain, but increased the expression of arginine decarboxylase and polyamines levels in the liver. d-Arg, the supposedly inert isomer, also unexpectedly affected the expression of some enzymes and metabolites. In conclusion, both l- and d-Arg significantly affected enzymes and metabolites in several pathways that use arginine as a substrate and further studies with different doses and treatment durations are planned to establish their safety or adverse effects to guide their use as oral supplements.


Assuntos
Arginina/administração & dosagem , Arginina/metabolismo , Suplementos Nutricionais , Administração Oral , Animais , Arginase/efeitos dos fármacos , Arginase/metabolismo , Arginina/farmacologia , Transportador 1 de Aminoácidos Catiônicos/efeitos dos fármacos , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Creatina/efeitos dos fármacos , Creatina/metabolismo , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Nitratos/sangue , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Nitritos/sangue , Ratos , Ratos Sprague-Dawley
12.
Artigo em Inglês | MEDLINE | ID: mdl-31521749

RESUMO

The aim of this study was to determine whether purinergic signaling is a pathway associated with fumonisin B1 (FB1)-induced impairment of immune and hemostatic responses. We also determined whether dietary supplementation with diphenyl diselenide (Ph2Se2) prevents or reduces these effects. Splenic nucleoside triphosphate diphosphohydrolase (NTPDase) activity for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) as substrates and total blood thrombocytes counts were significant lower in silver catfish fed with FB1-contaminated diets than in fish fed with a basal diet, while splenic adenosine deaminase (ADA) activity and metabolites of nitric oxide (NOx) levels were significant higher. Also, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significant lower in silver catfish fed with FB1-contaminated diets than in fish fed with a basal diet. Dietary supplementation with 3 mg Ph2Se2/kg of feed effectively modulated splenic NTPDase (ATP as substrate), ADA, GPx and SOD activities, as well as NOx levels, and was partially effective in the modulation of spleen NTPDase activity (ADP as substrate) and total blood thrombocytes count. These data suggest that splenic purinergic signaling of silver catfish fed with FB1-contaminated diets generates a pro-inflammatory profile that contributes to impairment of immune and inflammatory responses, via reduction of splenic ATP hydrolysis followed possible ATP accumulation in the extracellular environment. Reduction of ADP hydrolysis associated with possible accumulation in the extracellular environment can be a pathophysiological response that restricts the hemorrhagic process elicited by FB1 intoxication. Supplementation with Ph2Se2 effectively modulated splenic enzymes associated with control of extracellular nucleotides (except ADP; that was partially modulated) and nucleosides, thereby limiting inflammatory and hemorrhagic processes.


Assuntos
Ração Animal/análise , Derivados de Benzeno/farmacologia , Peixes-Gato , Doenças dos Peixes/induzido quimicamente , Fumonisinas/toxicidade , Compostos Organosselênicos/farmacologia , Baço/efeitos dos fármacos , Animais , Plaquetas , Dieta/veterinária , Contaminação de Alimentos , Glutationa Peroxidase/metabolismo , Nitratos/sangue , Nitritos/sangue , Transdução de Sinais , Superóxido Dismutase/metabolismo
13.
Phytother Res ; 34(2): 340-348, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31833621

RESUMO

Codonopsis lanceolata (CL) extract was shown to have antihypertensive effects in hypertensive rats. This randomized controlled trial was designed to investigate the ability of CL extract to prevent hypertension (HTN) in prehypertensive subjects. Eighty subjects aged 19-60 years with a systolic blood pressure (BP) of 120-139 mmHg and a diastolic BP of 80-89 mmHg were recruited over 3 months. Subjects were randomized 1:1 to a CL group and a placebo (PL) group and administered CL extract and starch, respectively, for 6 weeks. (BP) was measured and blood sampled at baseline and at the end of the trial. Relative to baseline, systolic BP was significantly decreased, and catalase activity was significantly increased following CL treatment in both the elevated systolic BP and stage 1 HTN subgroups. In the elevated systolic BP subgroup, serum nitrite concentration relative to baseline was significantly increased in CL compared to PL treated subjects (p = .038). In subjects with stage 1 HTN, high sensitivity C-reactive protein (p = .020) and malondialdehyde (p = .039) showed significantly greater reductions from baseline in the CL than in the PL group. In summary, CL was effective in preventing endothelial dysfunction, inflammation, and lipid peroxidation in prehypertensive subjects, with these effects differing according to baseline systolic BP levels.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Codonopsis/química , Extratos Vegetais/uso terapêutico , Pré-Hipertensão/tratamento farmacológico , Adulto , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Feminino , Humanos , Peroxidação de Lipídeos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Nitritos/sangue , Adulto Jovem
14.
Oxid Med Cell Longev ; 2019: 5382843, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827679

RESUMO

Stroke survivors are at substantial risk of recurrent cerebrovascular event or cardiovascular disease. Exercise training offers nonpharmacological treatment for these subjects; however, the execution of the traditional exercise protocols and adherence is constantly pointed out as obstacles. Based on these premises, the present study investigated the impact of an 8-week dynamic resistance training protocol with elastic bands on functional, hemodynamic, and cardiac autonomic modulation, oxidative stress markers, and plasma nitrite concentration in stroke survivors. Twenty-two patients with stroke were randomized into control group (CG, n = 11) or training group (TG, n = 11). Cardiac autonomic modulation, oxidative stress markers, plasma nitrite concentration, physical function and hemodynamic parameters were evaluated before and after 8 weeks. Results indicated that functional parameters (standing up from the sitting position (P = 0.011) and timed up and go (P = 0.042)) were significantly improved in TG. Although not statistically different, both systolic blood pressure (Δ = -10.41 mmHg) and diastolic blood pressure (Δ = -8.16 mmHg) were reduced in TG when compared to CG. Additionally, cardiac autonomic modulation (sympathovagal balance-LF/HF ratio) and superoxide dismutase were improved, while thiobarbituric acid reactive substances and carbonyl levels were reduced in TG when compared to the CG subjects. In conclusion, our findings support the hypothesis that dynamic resistance training with elastic bands may improve physical function, hemodynamic parameters, autonomic modulation, and oxidative stress markers in stroke survivors. These positive changes would be associated with a reduced risk of a recurrent stroke or cardiac event in these subjects.


Assuntos
Estresse Oxidativo , Treinamento de Resistência , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/patologia , Idoso , Pressão Sanguínea , Doença Crônica , Feminino , Força da Mão , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidases/metabolismo , Nitritos/sangue , Carbonilação Proteica , Acidente Vascular Cerebral/metabolismo , Superóxido Dismutase/metabolismo , Sobreviventes
15.
Biol Pharm Bull ; 42(12): 2076-2082, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787722

RESUMO

The cyclitol bornesitol is the main constituent of the leaves from the antihypertensive medicinal plant Hancornia speciosa. This study aimed to investigate the ability of bornesitol to reduce blood pressure and its mechanism of action. Normotensive Wistar rats were divided into control group and bornesitol groups treated intravenously with bornesitol (0.1, 1.0 and 3.0 mg/kg). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded in non-anesthetized awake animals. Nitric oxide (NO) and angiotensin-converting enzyme (ACE) were measured in plasma by using colorimetric methods. Vascular reactivity study was performed in rat aorta rings and the involvement of nitric oxide synthase (NOS), calcium-calmodulin complex and phosphatidylinositol-3-kinase (PI3K)/Akt pathway in the vasodilator effect was investigated. Administration of bornesitol significantly reduced the SBP, increased the plasmatic level of nitrite, and decreased ACE activity in normotensive rats. In the rat aorta, bornesitol induced endothelium-dependent vasodilatation, which was abolished by NOS blockade. While calcium-calmodulin complex inhibition decreased the vasodilator effect of bornesitol, the inhibition of PI3K/Akt pathway did not alter it. Bornesitol reduced the blood pressure by a mechanism involving an increased production or bioavailability of NO, inhibition of ACE, and by an endothelium- and NO-dependent vasodilator effect. The present results support the use of bornesitol as an active marker for the cardiovascular activity of Hancornia speciosa.


Assuntos
Anti-Hipertensivos/farmacologia , Apocynaceae , Ciclitóis/farmacologia , Vasodilatadores/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Brasil , Masculino , Óxido Nítrico/sangue , Nitritos/sangue , Peptidil Dipeptidase A/sangue , Folhas de Planta , Plantas Medicinais , Ratos Wistar
16.
Wiad Lek ; 72(9 cz 2): 1781-1785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622266

RESUMO

OBJECTIVE: Introduction: Polytrauma or multiple organ damage is associated with shock and lead to systemic inflammation, oxidative stress and endothelial dysfunction. A severe mechanical injury causes an increased proinflammatory mediators and cytokines levels. Among them, the overproduction of nitric oxide and its oxidation products play a key role in tissue damage. The aim: To evaluate the changes in dynamics of some ornithine cycle components levels during acute period of polytrauma. PATIENTS AND METHODS: Materials and methods: We measured standard biomechanical parameters and serum levels of NO, sum of nitrite and nitrate (NOx), L-arginine, arginase, and peroxynitrite. According to the ISS, the study included patients with moderate (n=15) to severe (n=15) polytrauma. RESULTS: Results: In 24 hours after polytrauma on the background of intensive care, it was observed significant increasing of NO, NOx, and arginase levels (severe cases) with decreasing of L-arginine and peroxynitrite levels. CONCLUSION: Conclusions: Elevated NO and NOx serum levels in patients with polytrauma is associated with increasing of arginase activity with decreasing of L-arginine and peroxynitrite levels on the background of intensive care.


Assuntos
Traumatismo Múltiplo/diagnóstico , Ornitina/metabolismo , Arginase/sangue , Arginina/sangue , Humanos , Traumatismo Múltiplo/sangue , Nitratos/sangue , Óxido Nítrico/sangue , Nitritos/sangue , Ácido Peroxinitroso/sangue
17.
J Manipulative Physiol Ther ; 42(6): 385-398, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31371096

RESUMO

OBJECTIVE: The purpose of our study was to evaluate the effect of manually assisted lumbar spinal manipulation therapy on tactile allodynia, peripheral nerve functional recovery, and oxidative markers in rats exposed to knee immobilization-inducing hypersensitivity. METHODS: Tactile allodynia and sciatic, tibial, and peroneal functional indices were assessed before the knee joint immobilization, 24 hours after the knee cast removal, and 24 hours after 3 weeks of lumbar therapy with the Activator Adjusting Instrument, model 4 (AAI 4). Subsequently, the blood was collected from each rat, and oxidative markers such as lipid hydroperoxide levels; nitric oxide metabolites; and superoxide dismutase, catalase, and glutathione peroxidase activities were assessed. RESULTS: The AAI 4 improved the immobilization-induced allodynia and recovered the peripheral nerve functional indices impaired after knee immobilization. Immobilized rats treated with AAI 4 therapy presented a lack of significant changes in lipid hydroperoxides and nitric oxide metabolites in the plasma contrasting with rats that were kept freely in their cages, with no therapy applied, which presented elevated lipid hydroperoxides levels. Also, the antioxidant catalase enzymatic activity decreased in the blood of rats immobilized and treated with AAI 4. CONCLUSION: These results suggest that manually assisted lumbar spinal manipulation therapy modulates systemic oxidative stress, which possibly contributes to the analgesia and recovery of peripheral nerve functionality.


Assuntos
Hiperalgesia/terapia , Plexo Lombossacral/fisiologia , Manipulação da Coluna , Animais , Biomarcadores/sangue , Catalase/sangue , Glutationa Peroxidase/sangue , Hiperalgesia/etiologia , Imobilização/efeitos adversos , Peróxidos Lipídicos/sangue , Modelos Animais , Óxido Nítrico/sangue , Nitritos/sangue , Nociceptividade , Estresse Oxidativo , Ratos , Ratos Wistar , Joelho de Quadrúpedes , Superóxido Dismutase/sangue
18.
Int Wound J ; 16(6): 1294-1303, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31429187

RESUMO

Diabetic foot ulcer is one of the most frightened diabetic complications leading to amputation disability and early mortality. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, and reactive oxygen and nitrogen species as a pathogenic polymicrobial biofilm, overall contributing to wound chronification and host homeostasis imbalance. Intralesional infiltration of epidermal growth factor (EGF) has emerged as a therapeutic alternative to diabetic wound healing, reaching responsive cells while avoiding the deleterious effect of proteases and the biofilm on the wound's surface. The present study shows that intralesional therapy with EGF is associated with the systemic attenuation of pro-inflammatory markers along with redox balance recovery. A total of 11 diabetic patients with neuropathic foot ulcers were studied before and 3 weeks after starting EGF treatment. Evaluations comprised plasma levels of pro-inflammatory, redox balance, and glycation markers. Pro-inflammatory markers such as erythrosedimentation rate, C-reactive protein, interleukin-6, soluble FAS, and macrophage inflammatory protein 1-alpha were significantly reduced by EGF therapy. Oxidative capacity, nitrite/nitrate ratio, and pentosidine were also reduced, while soluble receptor for advanced glycation end-products significantly increased. Overall, our results indicate that the local intralesional infiltration of EGF translates in systemic anti-inflammatory and antioxidant effects, as in attenuation of the glycation products' negative effects.


Assuntos
Pé Diabético/tratamento farmacológico , Fator de Crescimento Epidérmico/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Idoso , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Quimiocina CCL3/sangue , Citocinas/sangue , Feminino , Humanos , Injeções Intralesionais , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Nitratos/sangue , Nitritos/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Cicatrização , Receptor fas/sangue
19.
Life Sci ; 234: 116772, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31422097

RESUMO

AIMS: Ligation of the urethra to create partial bladder outlet obstruction has widely been used as an animal model of bladder obstruction, although obstructive bladder dysfunction may be due to both mechanical and functional obstruction. Previous studies in rodents have demonstrated that long-term nitric oxide (NO) deficiency can lead to detrusor overactivity, and lack of NO may thus cause impairment of bladder outlet relaxation. The aim of this study was to define the characteristics of bladder and urethral dysfunction induced by chronic NO deficiency through both in vivo and in vitro investigations. MAIN METHODS: Rats were divided into two groups, and one group received an NO synthase inhibitor (Nω-nitro-L-arginine methyl ester hydrochloride: L-NAME) in the drinking water for 4 weeks. Bladder and urethral function were evaluated by continuous cystometry and isovolumetric cystometry. In vitro functional studies of detrusor strips and measurement of the mRNA and protein expression of an ischemic marker and a gap junction protein were also performed in separate rats. KEY FINDINGS: L-NAME administration raised blood pressure and decreased plasma nitrite/nitrate level compared to the control group. L-NAME treatment increased the frequency of bladder contractions and the residual volume, and elevated urethral pressure and bladder contraction pressure. In addition, carbachol-induced contraction was reduced in isolated detrusor strips from the L-NAME group, and bladder expression of HIF-1 and connexin 43 showed upregulation. SIGNIFICANCE: These findings suggest that chronic administration of L-NAME to rats induces bladder hyperactivity with residual urine, and may provide a useful model of functional bladder obstruction.


Assuntos
NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase/antagonistas & inibidores , Obstrução do Colo da Bexiga Urinária/induzido quimicamente , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Nitratos/sangue , Óxido Nítrico Sintase/metabolismo , Nitritos/sangue , Ratos , Ratos Sprague-Dawley , Uretra/metabolismo , Uretra/fisiopatologia , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/sangue
20.
Nutrients ; 11(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412548

RESUMO

This study investigated the exercise-induced changes in oxidative stress, nitric oxide (NO) metabolism and amino acid profile in plasma of omnivorous (OMN, n = 25), lacto-ovo-vegetarian (LOV, n = 25) and vegan (VEG, n = 23) recreational runners. Oxidative stress was measured as malondialdehyde (MDA), NO as nitrite and nitrate, and various amino acids, including homoarginine and guanidinoacetate, the precursor of creatine. All analytes were measured by validated stable-isotope dilution gas chromatographic-mass spectrometric methods. Pre-exercise, VEG had the highest MDA and nitrate concentrations, whereas nitrite concentration was highest in LOV. Amino acid profiles differed between the groups, with guanidinoacetate being highest in OMN. Upon acute exercise, MDA increased in the LOV and VEG group, whereas nitrate, nitrite and creatinine did not change. Amino acid profiles changed post-exercise in all groups, with the greatest changes being observed for alanine (+28% in OMN, +21% in LOV and +28% in VEG). Pre-exercise, OMN, LOV and VEG recreational runners differ with respect to oxidative stress, NO metabolism and amino acid profiles, in part due to their different dietary pattern. Exercise elicited different changes in oxidative stress with no changes in NO metabolism and closely comparable elevations in alanine. Guanidinoacetate seems to be differently utilized in OMN, LOV and VEG, pre- and post-exercise.


Assuntos
Aminoácidos/sangue , Dieta Vegetariana , Óxido Nítrico/sangue , Estresse Oxidativo , Corrida , Vegetarianos , Adulto , Biomarcadores/sangue , Estudos Transversais , Dieta Vegana , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Técnicas de Diluição do Indicador , Peroxidação de Lipídeos , Masculino , Malondialdeído/sangue , Nitratos/sangue , Nitritos/sangue , Fatores de Tempo , Veganos , Adulto Jovem
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