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1.
Prev Nutr Food Sci ; 26(4): 417-424, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35047438

RESUMO

Grapes and their derivatives have antioxidant and cardioprotective properties. Therefore, we hypothesized that grape juice (GJ) could improve vascular oxidative damage caused by chlorine radicals (OCl-), which are excessively produced in vascular tissue during cardiovascular diseases (mainly diabetes and hypertension). The antioxidant capacity of GJ was analyzed by an electrochemical method, followed by administration in rats (100 or 300 mg/kg/d, via the oral) for seven days. Then, rats were sacrificed, and their aortas were isolated and subjected to isometric recordings or immuno-histochemical analyses with or without exposure to OCl- (5, 20, or 100 µM, 60 min). Concentration-effect curves for acetylcholine (ACh) and sodium nitroprusside (SNP) were derived to analyze endothelium-dependent or independent vasore-laxation. The GJ presented with high antioxidant capacity, and treatment with GJ did not alter vascular relaxation induced by ACh or SNP. After exposure to OCl-, endothelium-denuded arteries showed preserved relaxation with SNP, whereas endothelium-intact arteries showed reduced relaxation with ACh. OCl- at various concentrations induced significantly decreased relaxation of arteries (80.6±4.2%, 55.4±4.7%, and 28.1±5.9%, respectively) vs. control arteries (96.8±2.4%). However, treatment with GJ prevented loss in relaxation caused by 5 and 20 µM OCl- and improved relaxation after exposure to 100 µM OCl-. Exposure to OCl- induced increased nitrotyrosine immunostaining of endothelial cell layers, which was improved by GJ treatment. Altogether, vascular damage caused by OCl- was prevented by treatment with GJ, and GJ prevented nitrosative stress in these vessels.

2.
Basic Clin Pharmacol Toxicol ; 127(6): 516-524, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32573044

RESUMO

Paracetamol (PAR) is the most frequently consumed non-prescription drug, yet it is well known to induce toxicity. Here, we have evaluated the effects of exercise training on vascular dysfunction induced by PAR. Rats were distributed among four groups: (a) Sedentary; (b) Exercise; (c) Sedentary+PAR; and (d) Exercise+PAR. The exercise comprised swimming 50 min/d, 5 d/wk for 6 weeks (+PAR in the last 2 weeks, at 400 mg/kg/d/p.o.). After killing, the rats' blood and aortas were collected for biochemical analysis of hepatic transaminases, TBARs reaction, glutathione, glutathione reductase, SOD, and catalase. In vitro vascular relaxation was measured using acetylcholine and sodium nitroprusside in the presence or absence of tiron (an antioxidant). Vascular protein expression (eNOS and sGC) also were analysed. Increased transaminases after PAR treatment were found to be reduced by exercise. Vasodilation was impaired by PAR only in the sedentary group. Exercise prevented alterations in lipoperoxidation and glutathione levels after PAR exposure. Glutaathione reductase and SOD also were increased by PAR but were normalized in the exercised group. Catalase activity and protein expressions did not change in any group. PAR treatment caused impairment in both vasodilation and redox balance; however, exercise training prevented the vascular and redox system dysfunction induced by PAR treatment.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Aorta Torácica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal , Vasodilatação/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Aorta Torácica/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxirredução , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Natação
3.
Arch Toxicol ; 93(7): 1955-1964, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31020376

RESUMO

Acetaminophen (APAP) is one of the most widely consumed drugs in the world. Studies have shown renal and hepatic damage as the direct result of high oxidative stress induced by APAP. Since the cardiovascular system is sensitive to oxidative stress and literature describes increased cardiovascular dysfunction in APAP consumers, this work aimed to evaluate harmful effects of APAP on the vascular system. Rats were exposed to APAP (400 mg/kg/day in drinking water) for 14 days. Plasma and aortas were collected and stored in - 80 °C and a selection of arteries was prepared for isometric tension recordings, morphological, immunohistochemical and protein expression analysis. The APAP-treated group presented increased transaminases (ALT/AST) and malondialdehyde levels in the plasma compared to controls. Lipid peroxidation, glutathione reductase and superoxide dismutase levels were increased in the plasma and arteries of the APAP group. Nevertheless, glutathione level was reduced as compared to control group. The vasodilation response to acetylcholine and sodium nitroprusside (0.1 nM to 10 µM) was also impaired after APAP treatment; however, the vascular relaxation was restored after treatment with vitamin C (100 µM). Arteries from the APAP group presented reduced wall thickness, collagen deposition, elastic fibers and increased immunoreactivity to nitrotyrosine. eNOS and sGC protein expression remained unchanged and were at similar levels as controls. These findings showed higher oxidative stress and impaired vasodilation in rats exposed to APAP. Furthermore, arteries presented reduced cell layers, collagen, elastin deposition and significantly increased immunoreactivity to nitrotyrosine after APAP treatment.


Assuntos
Acetaminofen/toxicidade , Aorta Torácica/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Estresse Oxidativo/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Endotélio Vascular/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Ratos , Ratos Wistar
4.
Curr Drug Saf ; 14(2): 109-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30806323

RESUMO

BACKGROUND: Some studies have linked the use of paracetamol (PAR) with adverse effects like wheezing, exacerbation of asthma symptoms and other respiratory problems. Other studies are inconclusive or deny this correlation. This makes the association between PAR and airway hypersensitivity very controversial and still under debate. OBJECTIVE: This work investigated if chronic treatment with PAR in rats could directly affect the contraction and relaxation for different stimulus in isolated airways. METHODS: Rats were treated for 2 weeks with PAR (400 mg/Kg, v.o.). The blood was collected for biochemical analysis (alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBARs reaction and glutathione) and isolated tracheal rings were prepared in organ bath to measure isometric tone after contractile and relaxant stimulus. RESULTS: Hepatic enzymes (ALT, AST) and lipid peroxidation were increased after PAR-treatment, while glutathione was decreased. Rats do not present any alteration in airway myocytes responsiveness, either to contractile or relaxant stimulus (i.e. cholinergic agonist, membrane depolarization, Ca2+ influx across sarcolemma, internal Ca2+ release from sarcoplasmic reticulum, Ca2+ channel blocking, ß-agonist and NOmediating relaxation). CONCLUSION: Despite increased oxidative stress and reduced antioxidant defense, chronic treatment with PAR does not induce airway hypersensitivity or risk of asthma in rats.


Assuntos
Acetaminofen/toxicidade , Asma/induzido quimicamente , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Asma/metabolismo , Carbacol/farmacologia , Glutationa/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Ratos , Ratos Wistar , Traqueia/efeitos dos fármacos
5.
Rev. bras. farmacogn ; 28(3): 325-332, May-June 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-958874

RESUMO

ABSTRACT The prevention of chronic and degenerative diseases, is a health concern deeply associated with oxidative stress. Such progressive phenomena can be avoided through exogenous antioxidant intake, which set up a reductant cascade, mopping up damaging free radicals. Medicinal herbs are commonly associated with high antioxidant potential, and hence their health benefits. The commerce of dried herbal extracts movements a big portion of developing countries economy. The determination of medicinal herbs the antioxidant activity capacity is of utmost importance. The assessment of antioxidant activity in phytotherapics is mostly achieved by spectrophotometric assays, however colored substances can produce interferences that do not occur in electroanalytical methods. Therefore, the aim of this paper is to compare spectrophotometric and voltammetric techniques to evaluate antioxidant activity in herbal drugs such as: Ginkgo biloba L., Camellia sinensis (L.) Kuntze, Theaceae; Hypericum perforatum L., Hypericaceae; Aesculus hippocastanum L., Sapindaceae; Rosmarinus officinalis L., Lamiaceae; Morinda citrifolia L., Rubiaceae; Centella asiatica (L.) Urb., Apiaceae; Trifolium pratense L., Fabaceae; Crataegus oxyacantha L., Rosaceae; and Vaccinium macrocarpon Aiton, Ericaceae. The spectrophotometric methods employed were DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and the Folin-Ciocalteu assays. The electroanalytical method used was voltammetry and it was developed a phenoloxidase based biosensor. The redox behavior observed for each herbal sample resulted in distinguishable voltammetric profiles. The highest electrochemical indexes were found to G. biloba and H. perforatum, corroborating to traditional spectrophotometric methods. Thus, the electroanalysis of herbal drugs, may be a promising tool for antioxidant potential assessment.

6.
Planta Med ; 83(10): 830-836, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28187467

RESUMO

Ellagic acid is described as having antioxidant and antiproliferative properties. Hence, it was hypothesized that ellagic acid could improve cardiovascular damage caused by hypertension. In this work, hypertension was induced in rats with Nω-Nitro-L-arginine methyl ester hydrochloride (60 mg/kg/day in drinking water) for 6 weeks. Ellagic acid was coadministered (10 or 30 mg/kg/day by gavage) between the second and sixth week. Blood pressure was recorded every week by tail-cuff plethysmography. After 6 weeks, the rats were sacrificed, the hearts and kidneys were weighed, and blood was collected. Aortas were isolated and set up to isometric recordings in an organ bath for histological assay and measuring of calcium content. Hypertension (233.6 ± 9.5 mmHg) was reduced (p < 0.01) by treatment with ellagic acid 10 or 30 mg/kg. The blood levels of nitrate/nitrite were reduced in hypertensive rats and the ellagic acid restored these levels. While the vascular relaxations to acetylcholine and sodium nitoprusside and the contraction to phenylephrine were impaired in the hypertensive group, they were improved after ellagic acid treatment. The alkaline phosphatase activity was increased by hypertension and returned to control levels after ellagic acid treatment. In the aorta, the administration of ellagic acid resulted in less aortic wall thickening and less calcification. In conclusion, ellagic acid attenuates hypertension, possibly improving nitric oxide bioavailability. The vascular response to acetylcholine, sodium nitroprusside, and phenylephrine was impaired by hypertension and improved after treatment with ellagic acid. Moreover, plasmatic alkaline phosphatase activity, calcium content, and hypertrophy in vascular tissues during hypertension were attenuated by treatment with ellagic acid.


Assuntos
Antioxidantes/uso terapêutico , Cardiotônicos/uso terapêutico , Ácido Elágico/uso terapêutico , Coração/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/patologia , Masculino , Miocárdio/patologia , Ratos , Ratos Wistar , Calcificação Vascular/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos
7.
Oxid Med Cell Longev ; 2017: 2383157, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29422986

RESUMO

Jabuticaba is an exotic fruit native to Brazil that has been arousing medicinal interest. Using chemical (HPLC-PDA, resonance mass spectra, and NMR), electroanalytical (differential pulse voltammetry, radical scavenging assay), and pharmacological (in vivo and in vitro) approaches, we have identified its bioactive compounds and hypotensive effects on hypertensive rats. The hydroalcoholic extract of jabuticaba (HEJ) presents a great quantity of phenolic compounds, and several molecules with hydroxyl groups present high efficiency as an antioxidant. The treatment with HEJ (100 and 300 mg/kg/day, for four weeks) presented hypotensive effects on L-NAME-induced hypertensive rats, possibly improving the nitric oxide bioavailability because of its high antioxidant potential. Furthermore, renal and cardiac hypertrophies were also attenuated after the HEJ treatment. Moreover, the vascular responses to contractile and dilating agonists were improved with the HEJ treatment, which is also able to induce nitric oxide production in endothelial cells.


Assuntos
Frutas/química , Hipertensão/tratamento farmacológico , Myrtaceae/química , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Ratos
8.
Arq. bras. cardiol ; 107(3): 223-229, Sept. 2016. graf
Artigo em Inglês | LILACS | ID: lil-796033

RESUMO

Abstract Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect.


Resumo Fundamentos: Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. Objetivos: Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. Métodos: Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. Resultados: Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina também foi prejudicada pelo tratamento prévio com EHJ. A inibição da Ca2+ATPase do reticulo sarcoplasmático não alterou o relaxamento pelo EHJ. Além disso, o EHJ inibiu a contração causada pelo influxo de Ca2+ estimulado por fenilefrina e KCl (75 mM). Conclusão: O EHJ induz vasodilatação independente do endotélio. Ativação dos canais de K+ e inibição do influxo de Ca2+ através da membrana estão envolvidas no efeito relaxante do EHJ.


Assuntos
Animais , Masculino , Vasodilatadores/farmacologia , Extratos Vegetais/farmacologia , Myrtaceae/química , Músculo Liso Vascular/efeitos dos fármacos , Aorta Torácica/efeitos dos fármacos , Fatores de Tempo , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Verapamil/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Reprodutibilidade dos Testes , Ratos Wistar , Bloqueadores dos Canais de Potássio/farmacologia
9.
Arq Bras Cardiol ; 107(3): 223-229, 2016 Sep.
Artigo em Inglês, Português | MEDLINE | ID: mdl-27533258

RESUMO

BACKGROUND:: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. OBJECTIVES:: To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. METHODS:: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. RESULTS:: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). CONCLUSION:: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect. FUNDAMENTOS:: Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. OBJETIVOS:: Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. MÉTODOS:: Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. RESULTADOS:: Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina também foi prejudicada pelo tratamento prévio com EHJ. A inibição da Ca2+ATPase do reticulo sarcoplasmático não alterou o relaxamento pelo EHJ. Além disso, o EHJ inibiu a contração causada pelo influxo de Ca2+ estimulado por fenilefrina e KCl (75 mM). CONCLUSÃO:: O EHJ induz vasodilatação independente do endotélio. Ativação dos canais de K+ e inibição do influxo de Ca2+ através da membrana estão envolvidas no efeito relaxante do EHJ.


Assuntos
Músculo Liso Vascular/efeitos dos fármacos , Myrtaceae/química , Extratos Vegetais/farmacologia , Vasodilatadores/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Masculino , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/efeitos dos fármacos , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Verapamil/farmacologia
10.
Food Chem ; 190: 506-512, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26213003

RESUMO

The redox behavior of commercial roasted coffee products were evaluated by electroanalysis, whereas high performance liquid chromatography (HPLC) was used for determination of cinnamic acid markers, the total phenolic content (TPC) was achieved by Folin-Ciocalteu assay, and the traditional DPPH (1-diphenyl-2-picrylhydrazyl) method for antioxidant power determination. In turn, an optimized electrochemical index was proposed to estimate the antioxidant power of different samples and it was found a great correlation between all methods. The voltammetric profile of all coffee samples was quite similar, presenting the same number of peaks at the same potential values. Minor differences on current levels were in agreement with the total phenolic and major markers content, as well as, to the antioxidant power. Therefore, the electrochemical methods showed to be practical, low cost and very useful to evaluate the antioxidant properties of coffee samples, which is a relevant quality parameter of this widely consumed beverage.


Assuntos
Antioxidantes/química , Ácidos Cafeicos/química , Café/química , Eletroquímica/métodos , Fenóis/análise , Ácidos Cafeicos/análise , Cromatografia Líquida de Alta Pressão , Oxirredução
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