RESUMO
BACKGROUND: Increased generation of reactive oxygen and nitrogen species in chronic kidney disease (CKD) patients leads to increased oxidative stress. The antioxidant capacity of folic acid has been shown to scavenge radicals efficiently. OBJECTIVE: The current study was carried out to examine the effects of folic acid treatment on biochemical and oxidative stress biomarkers in patients in different stages of CKD. METHODS: This was a randomized, non-blinded, clinical trial that assessed the effects of 3 months of treatment with 5 mg of folic acid daily or no treatment in 113 outpatients within CKD stages 3a and 3b. At the end of the intervention, we analyzed the data of 66 patients treated with folic acid and 47 in the control group. Serum homocysteine levels and biochemical and oxidative/nitrosative stress biomarkers were analyzed in all patients. RESULTS: In most patients, folic acid treatment normalized homocysteine levels and increased antioxidant enzyme activity (paraoxonase 1) and decreased sulfhydryl (SH) groups. In addition, oxidative biomarkers (products of nitric oxide and lipid hydroperoxide) were significantly lower post-treatment compared to baseline in the active intervention group. In the no active intervention group, no statistically significant effects were found on the oxidative and biochemical biomarkers. CONCLUSION: Folic acid treatment in stages 3a-4 CKD patients effectively ameliorated their hyperhomocysteinemia and increased the activity of antioxidant enzymes, as well as decreased the levels of pro-oxidant biomarkers in stage G3a and G3b CKD patients. Folic acid treatment attenuated oxidative/nitrosative stress and may be considered as a possible strategy to improve redox status and diminish the damages associated with oxidative/nitrosative stress in CKD patients. Further studies are needed to confirm these findings. Clinical Trials Registration No.: This study is registered in the Brazilian Record of Clinical Trials (ReBEC), under reference RBR-2bfthr.
Assuntos
Antioxidantes/administração & dosagem , Ácido Fólico/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Antioxidantes/farmacologia , Feminino , Ácido Fólico/farmacologia , Humanos , Hiper-Homocisteinemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estresse Nitrosativo/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Resultado do TratamentoRESUMO
Evidence demonstrates the pronounced anti-inflammatory activity of a beetroot (Beta vulgaris) dye enriched in betalains obtained using precipitation with ethanol. Herein, we expand upon our previous observations and demonstrate the analgesic and antioxidant effect of betalains. Betalains [10-1000 mg/kg; intraperitoneal route (i.p.)] diminished acetic acid- and PBQ-induced abdominal contortions, and the overt pain-like behaviour induced by complete Freund`s adjuvant (CFA) and formalin (intraplantar; i.pl.) injection. Moreover, betalains (100 mg/kg) administered by various routes [i.p. or subcutaneous (s.c.)] or as a post-treatment reduced carrageenin- or CFA-induced hyperalgesia. Mechanistically, betalains mitigated carrageenin-induced tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, superoxide anion levels, and lipid peroxidation. Betalains also stopped the depletion of reduced glutathione (GSH) levels and ferric reducing ability produced by carrageenin, as well as upregulated Nrf2 and Ho1 transcript expression in the plantar tissue of mice. Furthermore, betalains showed hydroxyl radical, 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS+), and 2,2-diphenyl-1-picryl-hydrazyl radical (DPPHâ¢) scavenging ability and iron-chelating activity (bathophenantroline assay), and inhibited iron-independent and iron-dependent lipid peroxidation (LPO) in vitro. Finally, betalains-treated bone marrow-derived macrophages exhibited lower levels of cytokines (TNF-α and IL-1ß), and superoxide anion levels and nuclear factor kappa B (NF-κB) activation following lipopolysaccharide (LPS) stimulation. Therefore, this betalain-rich dye extracted using a novel precipitation approach presents prominent analgesic effect in varied models of pain by mechanisms targeting cytokines and oxidative stress.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Beta vulgaris/química , Betalaínas/farmacologia , Inflamação/tratamento farmacológico , Animais , Carragenina/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Dor/induzido quimicamente , Dor/metabolismo , Superóxidos/metabolismoRESUMO
Abstract Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber) and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC). A correlation was observed between TPC and antioxidant activity index (AAI) with a correlation coefficient (r2) of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies.
Resumo Os polifenóis são um grupo de metabólitos secundários vegetais que possuem uma variedade de bioatividades conhecidas, dentre elas a capacidade de funcionar como antioxidantes. Devido aos efeitos colaterais do uso excessivo de substâncias sintéticas, a busca por compostos naturais e menos tóxicos têm aumentado significativamente. Esse estudo teve por objetivo avaliar a atividade antioxidante e o teor de polifenóis dos extratos hexânicos, acetato de etila e aquosos de cascas (súber), caules, folhas jovens e folhas maduras de Blepharocalyx salicifolius. Os extratos foram obtidos por meio de extração com solventes orgânicos e subsequente fracionamento em cromatografia por coeficiente de partição. Testes preliminares da presença de compostos com atividade antioxidante foram realizados por meio de bioautografia em cromatografia de camada delgada. Os extratos foram submetidos ao teste da capacidade sequestrante do radical 2,2-difenil-1-picrilhidrazil (DPPH) para quantificação da atividade antioxidante e submetidos ao teste com o reagente de Folin-Ciocalteu para quantificação dos polifenóis. Os resultados mostraram que dos 12 extratos avaliados, 9 apresentaram atividade antioxidante muito forte e 3 atividade moderada. Os extratos aquosos de folhas jovens e cascas e o extrato acetato de etila de folhas jovens apresentaram os maiores índices de atividade antioxidante e teor de polifenóis (TPC). A correlação entre TPC e o índice de atividade antioxidante (AAI) observada foi de r2 = 0,7999. Dessa forma, ficou evidenciado o elevado teor de polifenóis e sua correlação com a atividade antioxidante nos extratos de B. salicifolius, fornecendo subsídios para novos estudos.
Assuntos
Fenóis/análise , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Myrtaceae , Componentes Aéreos da Planta/química , Antioxidantes/análise , Oxirredução/efeitos dos fármacos , Picratos , Compostos de Bifenilo , BrasilRESUMO
Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber) and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC). A correlation was observed between TPC and antioxidant activity index (AAI) with a correlation coefficient (r2) of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies.(AU)
Os polifenóis são um grupo de metabólitos secundários vegetais que possuem uma variedade de bioatividades conhecidas, dentre elas a capacidade de funcionar como antioxidantes. Devido aos efeitos colaterais do uso excessivo de substâncias sintéticas, a busca por compostos naturais e menos tóxicos têm aumentado significativamente. Esse estudo teve por objetivo avaliar a atividade antioxidante e o teor de polifenóis dos extratos hexânicos, acetato de etila e aquosos de cascas (súber), caules, folhas jovens e folhas maduras de Blepharocalyx salicifolius. Os extratos foram obtidos por meio de extração com solventes orgânicos e subsequente fracionamento em cromatografia por coeficiente de partição. Testes preliminares da presença de compostos com atividade antioxidante foram realizados por meio de bioautografia em cromatografia de camada delgada. Os extratos foram submetidos ao teste da capacidade sequestrante do radical 2,2-difenil-1-picrilhidrazil (DPPH) para quantificação da atividade antioxidante e submetidos ao teste com o reagente de Folin-Ciocalteu para quantificação dos polifenóis. Os resultados mostraram que dos 12 extratos avaliados, 9 apresentaram atividade antioxidante muito forte e 3 atividade moderada. Os extratos aquosos de folhas jovens e cascas e o extrato acetato de etila de folhas jovens apresentaram os maiores índices de atividade antioxidante e teor de polifenóis (TPC). A correlação entre TPC e o índice de atividade antioxidante (AAI) observada foi de r2 = 0,7999. Dessa forma, ficou evidenciado o elevado teor de polifenóis e sua correlação com a atividade antioxidante nos extratos de B. salicifolius, fornecendo subsídios para novos estudos.(AU)