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1.
J Med Food ; 24(2): 161-171, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32543960

RESUMO

The Asteraceae family is widely known for its therapeutic, aromatic, and nutritional properties. Chaptalia nutans (C. nutans), a member of the family, is widely used in folk medicine in southern Brazil. In this study, we aim to assess compounds present in root extracts of C. nutans, and evaluate their antioxidant capacity and toxicity. To determine the chemical composition of the extract, was performed through Liquid Chromatography coupled with Mass Spectroscopy. Antioxidant capacity, toxicity (Artemia salina biosassay), cytotoxicity, genotoxicity (Allium cepa test), and neurotoxicity (Drosophila melanogaster model) were evaluated. A large number of bioactive phytoconstituents were determined to be present, such as alkaloids, coumarins, flavonoids, terpenes, and especially phenolic compounds, which may explain the antioxidant capacity of the extract. Extracts had the capacity to protect cells from protein and lipid damage, and inhibit the formation of oxygen radicals. The A. salina bioassay revealed that extracts were only slightly toxic. In A. cepa, cells exposed to 1.5 mg/mL extract were protected against chromosomal damage caused by glyphosate, and had mitotic index values that were reduced by 49%. A concentration of 10 mg/mL extract did not kill flies, and when coadministered with paraquat (PQ) (52.5%) produced a mortality rate of only 18.75%. These findings indicated that the extract had the potential to protect against PQ-induced neurotoxicity. Taken together, these data reveal for the first time that the root extract of C. nutans is a rich source of natural antioxidants. The extract may be useful in the food and pharmaceutical industries.


Assuntos
Antioxidantes , Artemia , Asteraceae , Drosophila melanogaster , Cebolas , Extratos Vegetais , Raízes de Plantas , Animais , Antioxidantes/farmacologia , Artemia/efeitos dos fármacos , Asteraceae/química , Brasil , Dano ao DNA/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Cebolas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Raízes de Plantas/química
2.
J Med Food ; 24(6): 660-665, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33179973

RESUMO

Yacon is an Andean plant that has been used in folk medicine for its medicinal properties. The beneficial effects of this plant are possibly due to the high content of phenolic compounds present in its leaves and roots. This study evaluated the in vitro toxicity of the hydroalcoholic extract of leaves and roots from yacon (1, 10, 50, and 100 µg/mL) through cell viability tests, genotoxic and mutagenic activity in leukocytes culture cells; and cytotoxicity and apoptosis cell death (1, 10, 50, 100, and 500 µg/mL) in cell line originally established from the primary mouse embryonic fibroblast cells that were cultured by the designated protocol, so-called 3T3 protocol "3-day transfer, inoculum 3 × 105 cells" (3T3 cell line). No mutagenic and cytotoxic activities were observed in leukocyte cultures. Cytotoxic activity was evidenced in the highest concentrations of yacon leaf extract (50 and 100 µg/mL), whereas all concentrations tested with yacon leaf extract there was induction for apoptosis in the 3T3 cells. Genotoxic potential was observed only at higher doses of leaf (50 and 100 µg/mL) and root (100 µg/mL) extract. These results suggest that yacon leaf at high concentrations may present toxic potential showing concentration-dependent behavior; however, in vivo studies should be performed to validate these results.


Assuntos
Asteraceae , Extratos Vegetais , Animais , Sobrevivência Celular , Fibroblastos , Camundongos , Fenóis/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta
3.
J Med Food ; 23(7): 689-698, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31800339

RESUMO

Obesity reaches an epidemic level worldwide, and this condition is associated with chronic low-grade inflammation and secondary comorbidities, largely driven by global changes in lifestyle and diet. Various dietary approaches are proposed for the obesity treatment and its associated metabolic disorders. Good taste, antioxidant functions, and vitamins have been attributed to virgin coconut oil (VCO). However, VCO contains a large amount of saturated fatty acids, and the consumption of this fat is associated with a number of secondary diseases. We evaluate the effects of VCO supplementation on biochemical, inflammatory, and oxidative stress parameters in rats fed with high-fat diet (HFD). After feeding with HFD for 12 weeks, the animals were supplemented with VCO for 30 days. HFD+VCO group increased in diet intake, weight gain, low-density lipoprotein cholesterol level, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. These findings were accompanied by increased in hepatic lipid profile and fat deposition in the liver. Adipocyte hypertrophy was observed in the HFD+VCO group, which was associated with elevated expression of tumor necrosis factor alpha (TNF-α) in adipose tissue. These results revealed that VCO associated with HFD induced important metabolic alterations, adipose inflammation, and hepatic lipid accumulation in rats.


Assuntos
Tecido Adiposo , Óleo de Coco/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Inflamação , Fígado , Doenças Metabólicas/induzido quimicamente , Tecido Adiposo/fisiopatologia , Animais , Inflamação/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/fisiopatologia , Ratos
4.
Arch Biochem Biophys ; 668: 16-22, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047871

RESUMO

3-hydroxy-3-methylglutaric aciduria (HMGA) is an inherited disorder of the leucine catabolic pathway in which occurs a deficiency of the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme. Therefore, the organic acids 3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA), mainly, accumulate in tissues of affected patients. Lately, much attention has been focused on free radicals as mediators of tissue damage in human diseases, causing lipid peroxidation, protein oxidation and DNA damage. The treatment of this disease is based in a restricted protein ingest and supplementation with l-carnitine (LC), an antioxidant and detoxifying agent. In the present work, we investigated the in vitro oxidative damage to DNA induced by the accumulation of organic acids and oxidative stress parameters in vivo of patients with 3-HMG, as well as the effect of the recommended therapy. The in vitro DNA damage was analyzed by the alkaline comet assay in leukocytes incubated with HMG and MGA (1 mM, 2.5 mM and 5 mM) and co-incubated with LC (90 µM and 150 µM). The in vivo urinary 15-F2t-isoprostane levels and urinary oxidized guanine species were measured by ELISA kits in patient's urine before and after the treatment with LC. HMG and MGA induced a DNA damage index (DI) significantly higher than that of the control group. The DI was significantly reduced in the presence of LC. It was also verified a significant increase of oxidized guanine species and urinary isoprostane levels, biomarker of oxidative DNA damage and lipid peroxidation respectively, in patients before treatment. After the treatment and supplementation with LC, patients presented significantly lower levels of those biomarkers. Analyzing the data together, we can conclude that HMGA patients present oxidative lipid and DNA damage, which is induced by HMG and MGA, and the antioxidant therapy with LC can prevent that kind of injuries.


Assuntos
Acetil-CoA C-Acetiltransferase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Carnitina/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Meglutol/análogos & derivados , Meglutol/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/urina , Acetil-CoA C-Acetiltransferase/metabolismo , Acetil-CoA C-Acetiltransferase/urina , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/urina , Criança , Pré-Escolar , Dinoprosta/análogos & derivados , Dinoprosta/urina , Guanina/análogos & derivados , Guanina/urina , Guanosina/análogos & derivados , Guanosina/urina , Humanos , Lactente , Peroxidação de Lipídeos/efeitos dos fármacos
5.
Toxicol In Vitro ; 57: 194-202, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30853490

RESUMO

Maple syrup urine disease (MSUD) is an inherited deficiency of the branched-chain α-keto dehydrogenase complex, characterized by accumulation of the branched-chain amino acids (BCAAs) and their respective branched chain α-keto-acids (BCKAs), as well as by the presence of alloisoleucine (Allo). Studies have shown that oxidative stress is involved in the pathophysiology of MSUD. In this work, we investigated using the comet assay whether Allo, BCAAs and BCKAs could induce in vitro DNA damage, as well as the influence of l-Carnitine (L-Car) upon DNA damage. We also evaluated urinary 8-hydroxydeoguanosine (8-OHdG) levels, an oxidative DNA damage biomarker, in MSUD patients submitted to a restricted diet supplemented or not with L-Car. All tested concentrations of metabolites (separated or incubated together) induced in vitro DNA damage, and the co-treatment with L-Car reduced these effects. We found that Allo induced the higher DNA damage class and verified a potentiation of DNA damage induced by synergistic action between metabolites. In vivo, it was observed a significant increase in 8-OHdG levels, which was reversed by L-Car. We demonstrated for the first time that oxidative DNA damage is induced not only by BCAAs and BCKAs but also by Allo and we reinforce the protective effect of L-Car.


Assuntos
Aminoácidos/administração & dosagem , Carnitina/uso terapêutico , Dano ao DNA , Suplementos Nutricionais , Doença da Urina de Xarope de Bordo , Substâncias Protetoras/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Aminoácidos/sangue , Aminoácidos/urina , Criança , Pré-Escolar , Ensaio Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Humanos , Doença da Urina de Xarope de Bordo/sangue , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/genética , Doença da Urina de Xarope de Bordo/urina
6.
J Cell Biochem ; 119(12): 10021-10032, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30129250

RESUMO

The deficiency of the enzyme glutaryl-CoA dehydrogenase, known as glutaric acidemia type I (GA-I), leads to the accumulation of glutaric acid (GA) and glutarilcarnitine (C5DC) in the tissues and body fluids, unleashing important neurotoxic effects. l-carnitine (l-car) is recommended for the treatment of GA-I, aiming to induce the excretion of toxic metabolites. l-car has also demonstrated an important role as antioxidant and anti-inflammatory in some neurometabolic diseases. This study evaluated GA-I patients at diagnosis moment and treated the oxidative damage to lipids, proteins, and the inflammatory profile, as well as in vivo and in vitro DNA damage, reactive nitrogen species (RNS), and antioxidant capacity, verifying if the actual treatment with l-car (100 mg kg-1 day-1 ) is able to protect the organism against these processes. Significant increases of GA and C5DC were observed in GA-I patients. A deficiency of carnitine in patients before the supplementation was found. GA-I patients presented significantly increased levels of isoprostanes, di-tyrosine, urinary oxidized guanine species, and the RNS, as well as a reduced antioxidant capacity. The l-car supplementation induced beneficial effects reducing these biomarkers levels and increasing the antioxidant capacity. GA, in three different concentrations, significantly induced DNA damage in vitro, and the l-car was able to prevent this damage. Significant increases of pro-inflammatory cytokines IL-6, IL-8, GM-CSF, and TNF-α were shown in patients. Thus, the beneficial effects of l-car presented in the treatment of GA-I are due not only by increasing the excretion of accumulated toxic metabolites, but also by preventing oxidative damage.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Encefalopatias Metabólicas/metabolismo , Carnitina/farmacologia , Dano ao DNA , Glutaril-CoA Desidrogenase/deficiência , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carnitina/uso terapêutico , Criança , Pré-Escolar , Feminino , Glutaril-CoA Desidrogenase/efeitos dos fármacos , Glutaril-CoA Desidrogenase/metabolismo , Humanos , Lactente , Masculino , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Espécies Reativas de Nitrogênio
7.
Neurotox Res ; 34(3): 538-546, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29730834

RESUMO

The aim of this study was to investigate the effect of ovariectomy (OVX), a surgical model of menopause, and/or vitamin D (VIT D) supplementation on oxidative status, DNA damage, and telomere length in hippocampus of rats at two ages. Ninety-day-old (adult) or 180-day-old (older) female Wistar rats were divided into four groups: SHAM, OVX, VIT D, and OVX + VIT D. Thirty days after OVX, rats were supplemented with VIT D (500 IU/kg) by gavage, for a period of 30 days. Results showed that OVX altered antioxidant enzymes, increasing the activities of catalase in adult rats and superoxide dismutase in older rats. VIT D per se increased the activities of catalase and superoxide dismutase in older rats, but not in adult rats. VIT D supplementation to OVX (OVX + VIT D) rats did not reverse the effect of OVX on catalase in adult rats, but it partially reversed the increase in superoxide dismutase activity in older rats. OVX increased DNA damage in hippocampus of adult and older rats. VIT D per se reduced DNA damage, and when associated to OVX, it partially reversed this alteration. Additionally, OVX caused a telomere shortening in older rats, and VIT D was able to reverse such effect. Taken together, these results demonstrate that surgical menopause in rats causes hippocampal biochemical changes and VIT D appears, at least in part, to act in a beneficial way.


Assuntos
Dano ao DNA/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Ovariectomia/efeitos adversos , Encurtamento do Telômero/fisiologia , Vitamina D/farmacologia , Fatores Etários , Animais , Catalase/metabolismo , Ensaio Cometa , Feminino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Superóxido Dismutase/metabolismo , Encurtamento do Telômero/efeitos dos fármacos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
8.
Biomed Pharmacother ; 97: 300-309, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29091879

RESUMO

Cardiovascular disease (CVD) are a major public health problem, as they are among the leading causes of mortality worldwide. Tripodanthus acutifolius (TA) is a hemiparasite plant used for medicinal purposes with great antioxidant capacity. However, little is known about its hypolipemic effect. Thus, the aim of this study was to evaluate the effects of the hydroalcoholic extract of Tripodanthus acutifolius leaves in hypercholesterolemic Wistar rats. The animals were divided into: (1) NC (Normocaloric Control); (2) HC (Hypercaloric Control); (3) Oral Simvastatin Suspension 10mg/kg (SIM); (4) TA extract 50mg/kg (TA 50mg/kg) and (5) TA 100mg/kg. The in vitro antioxidant activity assay demonstrated that TA shows high antioxidant capacity. The in vivo findings demonstrated that TA supplementation resulted in significant decreases (p<0.05) in Total Cholesterol (TC), Triglycerides (TG) and Low density lipoprotein (LDL) levels, whereas High density lipoprotein (HDL) levels increased significantly in all TA-supplemented groups in relation to the HC group. Hepatic, renal and cardiac function markers improved during supplementation. Serum adiponectin levels increased significantly, whereas C-reactive protein (PCRus) levels decreased in the TA-supplemented in relation to the HC group. Catalase (CAT), superoxide dismutase (SOD) and gluthatione peroxidase (GPx) activities, as well as polyphenols, vitamin C (VitC) and total gluthatione (GSH), increased significantly in the TA-supplemented groups treated when compared to the HC group. Concerning oxidative damage to biomolecules, TA showed a protective effect on lipids, proteins and DNA. Regarding the histological analysis of the aortic artery, TA treatment was able to decrease aortic vasculature. Therefore, TA is rich in antioxidant compounds and may be an alternative for the treatment of hypercholesterolemia.


Assuntos
Hipercolesterolemia/metabolismo , Hipercolesterolemia/prevenção & controle , Erva-de-Passarinho , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Relação Dose-Resposta a Droga , Etanol/uso terapêutico , Masculino , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Ratos , Ratos Wistar , Resultado do Tratamento , Água
9.
Biomed Pharmacother ; 98: 338-346, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29274591

RESUMO

Non-alcoholic fatty liver disease is a spectrum of liver changes, ranging from hepatic steatosis to hepatocellular carcinoma. The Citrus maxima (CM) has been shown to be beneficial to the organism, and these activities are attributed to the presence of phytochemical compounds. The objective of this study was to evaluate the n vitro antioxidant potential of the CM leaves extract and on Wistar rats submitted to hepatic steatosis induction by fructose-associated hyperlipid diet (FHD). For the evaluation of in vivo effects, the animals were distributed in G1 (normal diet - ND), G2 (FHD), G3 (ND + extract 50mg/kg) and G4 (FHD + extract 50 mg/kg). All the parameters were determined through classical methodologies. The extract showed a significant antioxidant potential in vitro. In the in vivo analysis, the diet used was able to induce the development of metabolic abnormalities that favored the formation of hepatic steatosis (G2). Changes in inflammatory markers, increase in markers of oxidative damage, and reduction of antioxidant defenses were also observed. In addition, the extract did not cause changes in the animals' weight gain and acted as an anti-inflammatory, since G4 animals exhibited significantly reduced levels of the inflammatory markers. In the liver, the extract significantly decreased the content of fat, cholesterol and triglycerides compared to G2. The extract also showed antioxidant activity (G4) when compared to G2. The results suggest that the extract of CM leaf showed hepatoprotective, hypolipidemic, anti-inflammatory and antioxidant activities and the presence of phenolic compounds is a probable cause for such activities.


Assuntos
Citrus/química , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
10.
J Food Sci ; 82(12): 3029-3036, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29083494

RESUMO

This study evaluated the protective effect of flaxseed oil (FO) and flaxseed lignan secoisolariciresinol diglucoside (SDG) against oxidative stress in rats with metabolic syndrome (MS). 48 rats were allocated into the following 6 groups: Groups 1 (control), 5 (FO), and 6 (SDG) received water and were treated daily orally with saline, FO, and SDG, respectively. Groups 2 (MS), 3 (MS+FO), and 4 (MS+SDG) received 30% fructose in drinking water for MS induction and were treated daily orally with saline, FO, and SDG, respectively. After 30 d, animals were sacrificed, and blood was collected for biochemical and oxidative analysis. Body weight was recorded weekly. Systolic blood pressure (SBP) was measured before and after treatment. Fructose could produce MS and oxidative stress. FO and SDG prevented changes in SBP, lipids, and glucose. FO and SDG prevented oxidative damage to lipids, and only FO prevented oxidative damage to proteins associated to MS. FO and SDG improved enzymatic antioxidants defenses and reduced glutathione levels, which was greater with SDG. Total polyphenol levels were enhanced in groups that received SDG. Thus, the results of this study demonstrated that treatment with a 30% fructose solution for 30 d is effective for MS induction and the oxidative stress is involved in the pathophysiology of MS induced by fructose-rich diets. Furthermore, we demonstrated that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content especially that of SDG, suggesting that this compound can be used in isolation to prevent oxidative stress associated with MS. PRACTICAL APPLICATION: We report that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content, especially that of secoisolariciresinol diglucoside. This is significant because suggests that this compound can be used in isolation to prevent oxidative stress associated with MS. Furthermore, this study was the only one to perform a comparison of the abilities of 2 components of flaxseed to protect against oxidative stress in an MS model, which brings a great advance in the medicine's field, since it indicates another alternative for improve the health and the quality of life of patients with this disorder.


Assuntos
Linho/química , Lignanas/metabolismo , Óleo de Semente do Linho/metabolismo , Síndrome Metabólica/prevenção & controle , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Peso Corporal , Butileno Glicóis , Frutose/metabolismo , Glucose/metabolismo , Glucosídeos , Humanos , Lipídeos/sangue , Masculino , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Substâncias Protetoras , Qualidade de Vida , Ratos
11.
Braz. J. Pharm. Sci. (Online) ; 53(2): e16098, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-839473

RESUMO

ABSTRACT The bark tea of Ceiba speciosa, a tropical tree of the Malvaceae family, is used in the Northwestern Region of Rio Grande do Sul state, Brazil, to reduce blood cholesterol levels. However, there are no scientific data on the efficacy and safety of this plant. The aim of the present study was to evaluate the in vitro antioxidant and toxic potential of bark extracts of C. speciosa. We performed a preliminary phytochemical analysis by high-performance liquid chromatography-diode array detection (HPLC-DAD) and evaluated the oxidative damage to proteins and lipids, the radical scavenging effect, and genotoxicity of the lyophilized aqueous extract (LAECs) and the precipitate obtained from the raw ethanol extract (Cs1). The phytochemical profile demonstrated the presence of phenolic and flavonoid compounds. The LAECs and Cs1 prevented damage to lipids and proteins at concentrations of 50 and 10 µg/mL. They also showed a scavenging effect on 2,2-diphenyl-1-pricril-hydrazyl (DPPH) radicals in a concentration-dependent manner. Furthermore, no genotoxic effect was observed at concentrations of 10, 5 and 2 µg/mL in the Comet assay. The present study is the first evaluation regarding the characterization of C. speciosa and its safety, and the results demonstrate its antioxidant potential and suggest that its therapeutic use may be relatively safe.


Assuntos
Técnicas In Vitro/métodos , Toxicidade , Malvaceae/classificação , Compostos Fenólicos/classificação , Antioxidantes/análise , Plantas Medicinais/anatomia & histologia , Cromatografia Líquida de Alta Pressão/instrumentação , Ensaio Cometa/estatística & dados numéricos
12.
Int J Food Sci Nutr ; 66(5): 559-68, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26171628

RESUMO

The effects of supplementation with blueberry (BE) extract (Vaccinium ashei Reade) for 14 consecutive days on biochemical, hematological, histopathological and oxidative parameters in hypercholesterolemic rats were investigated. After supplementation with lyophilized extract of BE, the levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides were decreased. Histopathological analysis showed significant decrease (p < 0.05) of aortic lesions in hypercholesterolemic rats. Oxidative parameters showed significant reductions (p < 0.05) in oxidative damage to lipids and proteins and an increase in activities of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. The BE extract showed an important cardioprotective effect by the improvements in the serum lipid profile, antioxidant system, particularly in reducing oxidative stress associated with hypercholesterolemia and anti-atherogenic effect in rats.


Assuntos
Antioxidantes/uso terapêutico , Aterosclerose/prevenção & controle , Mirtilos Azuis (Planta) , Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/sangue , LDL-Colesterol/sangue , Suplementos Nutricionais , Frutas , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxirredução , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Triglicerídeos/sangue
13.
Gene ; 548(2): 294-8, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25046137

RESUMO

Maple syrup urine disease (MSUD) is an inherited aminoacidopathy caused by a deficiency in branched-chain α-keto acid dehydrogenase complex activity that leads to the accumulation of the branched-chain amino acids (BCAAs) leucine (Leu), isoleucine, and valine and their respective α-keto-acids, α-ketoisocaproic acid (KIC), α keto-ß-methylvaleric acid, and α-ketoisovaleric acid. The major clinical features presented by MSUD patients include ketoacidosis, failure to thrive, poor feeding, apnea, ataxia, seizures, coma, psychomotor delay, and mental retardation; however, the pathophysiology of this disease is poorly understood. MSUD treatment consists of a low protein diet supplemented with a mixture containing micronutrients and essential amino acids but excluding BCAAs. Studies have shown that oxidative stress may be involved in the neuropathology of MSUD, with the existence of lipid and protein oxidative damage in affected patients. In recent years, studies have demonstrated the antioxidant role of L-carnitine (L-Car), which plays a central function in cellular energy metabolism and for which MSUD patients have a deficiency. In this work, we investigated the in vitro effect of Leu and KIC in the presence or absence of L-Car on DNA damage in peripheral whole blood leukocytes using the alkaline comet assay with silver staining and visual scoring. Leu and KIC resulted in a DNA damage index that was significantly higher than that of the control group, and L-Car was able to significantly prevent this damage, mainly that due to KIC.


Assuntos
Carnitina/farmacologia , Dano ao DNA/efeitos dos fármacos , Cetoácidos/metabolismo , Leucina/metabolismo , Doença da Urina de Xarope de Bordo/metabolismo , Complexo Vitamínico B/farmacologia , Ensaio Cometa , Metabolismo Energético/efeitos dos fármacos , Humanos , Leucócitos/metabolismo , Doença da Urina de Xarope de Bordo/patologia , Estresse Oxidativo
14.
Int J Biochem Cell Biol ; 54: 20-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24980685

RESUMO

The present study investigated the effects of hyperprolinemia on oxidative damage to biomolecules (protein, lipids and DNA) and the antioxidant status in blood of rats. The influence of the antioxidants on the effects elicited by proline was also examined. Wistar rats received two daily injections of proline and/or vitamin E plus C (6th-28th day of life) and were killed 12h after the last injection. Results showed that hyperprolinemia induced a significant oxidative damage to proteins, lipids and DNA demonstrated by increased carbonyl content, malondialdehyde levels and a greater damage index in comet assay, respectively. The concomitant antioxidants administration to proline treatment completely prevented oxidative damage to proteins, but partially prevented lipids and DNA damage. We also observed that the non-enzymatic antioxidant potential was decreased by proline treatment and partially prevented by antioxidant supplementation. The plasma levels of vitamins E and C significantly increased in rats treated exogenously with these vitamins but, interestingly, when proline was administered concomitantly with vitamin E plus C, the levels of these vitamins were similar to those found in plasma of control and proline rats. Our findings suggest that hyperprolinemia promotes oxidative damage to the three major classes of macromolecules in blood of rats. These effects were accomplished by decrease in non-enzymatic antioxidant potential and decrease in vitamins administered exogenously, which significantly decreased oxidative damage to biomolecules studied. These data suggest that antioxidants may be an effective adjuvant therapeutic to limit oxidative damage caused by proline.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/fisiopatologia , Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , DNA/química , Lipídeos/química , Estresse Oxidativo/efeitos dos fármacos , Prolina Oxidase/deficiência , Proteínas/química , 1-Pirrolina-5-Carboxilato Desidrogenase/deficiência , Animais , Ácido Ascórbico/farmacologia , Suplementos Nutricionais , Masculino , Malondialdeído/metabolismo , Oxirredução , Prolina/química , Ratos , Ratos Wistar , Vitamina E/farmacologia , Vitaminas/farmacologia
15.
Gene ; 539(2): 270-4, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24534463

RESUMO

High blood levels of homocysteine (Hcy) are found in patients affected by homocystinuria, a genetic disorder caused by deficiency of cystathionine ß-synthase (CBS) activity, as well as in nutritional deficiencies (vitamin B12 or folate) and in abnormal renal function. We previously demonstrated that lipid and protein oxidative damage is increased and the antioxidant defenses diminished in plasma of CBS-deficient patients, indicating that oxidative stress is involved in the pathophysiology of this disease. In the present work, we extended these investigations by evaluating DNA damage through the comet assay in peripheral leukocytes from CBS-deficient patients, as well as by analyzing of the in vitro effect of Hcy on DNA damage in white blood cells. We verified that DNA damage was significantly higher in the CBS-deficient patients under treatment based on a protein-restricted diet and pyridoxine, folic acid, betaine and vitamin B12 supplementation, when compared to controls. Furthermore, the in vitro study showed a concentration-dependent effect of Hcy inducing DNA damage. Taken together, the present data indicate that DNA damage occurs in treated CBS-deficient patients, possibly due to high Hcy levels.


Assuntos
Cistationina beta-Sintase/deficiência , Cistationina beta-Sintase/genética , Dano ao DNA , Homocisteína/sangue , Homocistinúria/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Ensaio Cometa , Cistationina beta-Sintase/sangue , Feminino , Seguimentos , Homocistinúria/sangue , Homocistinúria/enzimologia , Humanos , Masculino , Prognóstico , Adulto Jovem
16.
Int J Dev Neurosci ; 31(1): 21-4, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23137711

RESUMO

Maple syrup urine disease (MSUD) is an inborn error of metabolism biochemically characterized by elevated levels of the branched chain amino acids (BCAA) leucine, isoleucine, valine and the corresponding branched-chain α-keto acids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. l-Carnitine (l-Car) plays a central role in the cellular energy metabolism because it transports long-chain fatty acids for oxidation and ATP generation. In recent years many studies have demonstrated the antioxidant role of this compound. In this work, we investigated the effect of BCAA-restricted diet supplemented or not with l-Car on lipid peroxidation and in protein oxidation in MSUD patients. We found a significant increase of malondialdehyde and of carbonyl content in plasma of MSUD patients under BCAA-restricted diet compared to controls. Furthermore, patients under BCAA-restricted diet plus l-Car supplementation presented a marked reduction of malondialdehyde content in relation to controls, reducing the lipid peroxidation. In addition, free l-Car concentrations were negatively correlated with malondialdehyde levels. Our data show that l-Car may have an antioxidant effect, protecting against the lipid peroxidation and this could represent an additional therapeutic approach to the patients affected by MSUD.


Assuntos
Carnitina/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Doença da Urina de Xarope de Bordo/tratamento farmacológico , Doença da Urina de Xarope de Bordo/metabolismo , Proteínas/metabolismo , Complexo Vitamínico B/uso terapêutico , Aminoácidos/metabolismo , Análise de Variância , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Malondialdeído/metabolismo , Carbonilação Proteica/efeitos dos fármacos
17.
Molecules ; 17(1): 1113-23, 2012 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-22269829

RESUMO

Baccharis trimera is a plant popularly used as a tea and to treat gastrointestinal diseases and inflammatory processes as well. The total phenolic content was determined and the antioxidant and anti-inflammatory activities of six extracts (dichloromethane, ethyl acetate, butanol, aqueous, saponin and phenolic) from B. trimera were evaluated. Using carrageenan-induced pleurisy as a model of acute inflammation, the phenolic extract at 15 mg/kg decreased significantly the analyzed parameters when compared to the carrageenan group ( p < 0.05), thus showing potential anti-inflammatory activity. The total phenolic content and antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH methods, respectively. Phenolic and ethyl acetate extracts presented higher antioxidant activity ( p < 0.05) than ascorbic acid. The phenolic extract also showed the highest antioxidant potential in relation to the other extracts, thus suggesting that the antioxidant and anti-inflammatory activities were due to the presence of phenolic compounds.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Baccharis/química , Fenóis/química , Extratos Vegetais/farmacologia , Animais , Ácido Ascórbico/metabolismo , Compostos de Bifenilo/metabolismo , Carragenina , Feminino , Concentração Inibidora 50 , Óxido Nítrico/metabolismo , Picratos/metabolismo , Folhas de Planta/química , Pleurisia/patologia , Ratos , Ratos Wistar
18.
Arq Bras Cardiol ; 97(2): 141-7, 2011 Aug.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-22002029

RESUMO

BACKGROUND: Recent studies describe the participation of reactive oxygen and nitrogen species in hypertension. OBJECTIVE: To identify the redox imbalance in the blood of hypertensive. METHODS: Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), vitamin C, transferrin, ceruloplasmin, malondialdehyde (MDA) and carbonyl group were quantified in the blood of 20 hypertensives and 21 controls. The individuals had a Body Mass Index of ≥ 18.5 and ≤ 30 kg/m(2), glycemia ≤ 100 mg/dL, serum cholesterol ≤ 200 mg/dL, and were nonsmokers, non-pregnant and non-lactating women, non-users of alopurinol and probucol, with hypertensives on antihypertensive medication. All individuals underwent a preparatory period of 4 weeks without alcohol, vitamin supplements, dexamethasone and paracetamol. RESULTS: Reduced levels of CAT (p 0.013), GSH (p 0.003) and MDA (p 0.014), and high levels of GPx (p 0.001) and ceruloplasmin (p 0.015) were obtained in the hypertensive group compared with controls. A positive correlation between systolic pressure and MDA in hypertensive and diastolic pressure and CAT in controls was obtained. CONCLUSION: The data obtained suggest that the hypertensives were in redox imbalance, despite the possibly attenuating effect of their antihypertensive medication.


Assuntos
Antioxidantes/análise , Hipertensão/sangue , Estresse Oxidativo/fisiologia , Anti-Hipertensivos/uso terapêutico , Antioxidantes/metabolismo , Biomarcadores/sangue , Brasil , Catalase/sangue , Métodos Epidemiológicos , Feminino , Glutationa/sangue , Humanos , Hipertensão/tratamento farmacológico , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
19.
Braz. j. pharm. sci ; 47(3): 605-613, July-Sept. 2011. tab
Artigo em Inglês | LILACS | ID: lil-602678

RESUMO

The use of plant species is emerging as an important alternative in the treatment of injuries. Therefore, the extract of Sonchus oleraceus 10 percent was employed in the repair of skin lesions. A total of 36 male Wistar rats were subjected to a punch injury and divided into three groups: a negative control, receiving no treatment, a positive control, treated with Dersani, and the experimental group treated with the extract. The injury was assessed macroscopically and microscopically. Morphometric data was collected at the 3rd, 5th and 7th postoperative day, and the experimental group showed greater changes in shrinkage of the lesion compared to control groups. On the 3rd postoperative day, the injury in the experimental group showed less necrotic tissue, lower slough and more granulation tissue in relation to the positive control group. On the 7th and 10th postoperative day, the injury in the experimental group showed lower slough compared to the positive control group. Microscopic analysis of lesions on the 5th postoperative day revealed increased fibroplasia in the experimental group compared to control groups, while on the 14th postoperative day less neovascularization was evident in the experimental group and increased formation of hair follicles in the negative control group. The extract of S. oleraceus provided tissue repair in accordance with normal physiological patterns thus confirming empirical evidence for its use.


O emprego de espécies vegetais vem surgindo como alternativa no tratamento de lesões. Dessa forma, foi utilizado o extrato hidroalcoólico de Sonchus oleraceus a 10 por cento na reparação de lesões cutâneas. Trinta e seis ratos machos Wistar, foram submetidos a uma lesão com "punch" e distribuídos em três grupos: controle negativo, não recebeu tratamento; controle positivo, tratado com Dersani; e o experimental, tratado com extrato. A lesão foi avaliada macroscopicamente e microscopicamente. Os dados morfométricos mostraram que no 3º, 5º e 7º dia pós-operação (DPO), o grupo experimental apresentou maior evolução na retração da lesão em relação aos grupos controles. No 3° DPO a lesão do grupo experimental apresentou menor tecido necrótico, menor esfacelo e maior tecido de granulação em relação ao grupo controle positivo. No 7° e 10º DPO, a lesão do grupo experimental apresentou menor esfacelo em relação ao grupo controle positivo. A análise microscópica das lesões revelou no 5º DPO maior fibroplasia no grupo experimental em relação aos grupos controles; no 14º DPO ocorreu menor neovascularização no grupo experimental e maior formação de folículos pilosos no grupo controle negativo. O extrato hidroalcoólico de S. oleraceus propiciou reparo tecidual obedecendo a padrões fisiológicos normais e confirmando os dados empíricos de sua utilização.


Assuntos
Animais , Masculino , Adulto Jovem , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Pele , Pele/lesões , Pele/química , Ratos Wistar/lesões , Sonchus/toxicidade , Cicatrização , Ensaio Clínico , Farmacognosia , Interpretação Estatística de Dados , Terapêutica/estatística & dados numéricos
20.
Arq. bras. cardiol ; 97(2): 141-147, ago. 2011. tab
Artigo em Português | LILACS | ID: lil-601783

RESUMO

FUNDAMENTO: Estudos recentes descrevem a participação de espécies reativas de oxigênio e nitrogênio na hipertensão. OBJETIVO: Identificar o desbalanço redox em sangue de hipertensos. MÉTODOS: Superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GPx), glutationa (GSH), vitamina C, transferrina, ceruloplasmina, malondialdeído (MDA) e o grupo carbonila, foram quantificados no sangue de 20 hipertensos e 21 controles. Os indivíduos tinham um Índice de Massa Corporal de > 18,5 e < 30 kg/m², glicemia < 100 mg/dL, colesterol sérico < 200 mg/dL, e eram mulheres não fumantes, não grávidas e não lactantes, não usuárias de alopurinol e probucol, e hipertensos em medicação anti-hipertensiva. Todos os indivíduos foram submetidos a um período preparatório de quatro semanas sem álcool, suplementos vitamínicos, dexametasona e paracetamol. RESULTADOS: Níveis reduzidos de CAT (p = 0,013), GSH ( p = 0,003) e MDA (p = 0,014), e altos níveis de GPx (p = 0,001) e ceruloplasmina (p = 0,015) foram obtidos no grupo de hipertensos, em comparação com os controles. Foi verificada uma correlação positiva entre a pressão sistólica e o MDA nos hipertensos e diastólica e CAT nos controles. CONCLUSÃO: Os dados obtidos são sugestivos de que os hipertensos apresentavam desequilíbrio em reações redox, a despeito do possível efeito atenuante de sua medicação anti-hipertensiva.


BACKGROUND: Recent studies describe the participation of reactive oxygen and nitrogen species in hypertension. OBJECTIVE: To identify the redox imbalance in the blood of hypertensive. METHODS: Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), vitamin C, transferrin, ceruloplasmin, malondialdehyde (MDA) and carbonyl group were quantified in the blood of 20 hypertensives and 21 controls. The individuals had a Body Mass Index of > 18.5 and < 30 kg/m², glycemia < 100 mg/dL, serum cholesterol < 200 mg/dL, and were nonsmokers, non-pregnant and non-lactating women, non-users of alopurinol and probucol, with hypertensives on antihypertensive medication. All individuals underwent a preparatory period of 4 weeks without alcohol, vitamin supplements, dexamethasone and paracetamol. RESULTS: Reduced levels of CAT (p 0.013), GSH (p 0.003) and MDA (p 0.014), and high levels of GPx (p 0.001) and ceruloplasmin (p 0.015) were obtained in the hypertensive group compared with controls. A positive correlation between systolic pressure and MDA in hypertensive and diastolic pressure and CAT in controls was obtained. CONCLUSION: The data obtained suggest that the hypertensives were in redox imbalance, despite the possibly attenuating effect of their antihypertensive medication.


FUNDAMENTO: Estudios recientes describen la participación de especies reactivas de oxígeno y nitrógeno en la hipertensión. OBJETIVO: Identificar el desequilíbrio redox em la sangre de los hipertensos MÉTODOS: El Superóxido dismutasa (SOD), catalasa (CAT), glutationa peroxidasa (GPx), glutationa (GSH), vitamina C, transferrina, ceruloplasmina, malondialdehído (MDA) y el grupo carbonilo, fueron cuantificados en la sangre de 20 hipertensos y 21 controles. Los individuos tenían un Índice de Masa Corporal de > 18,5 y < 30 kg/m², glicemia < 100 mg/dL, colesterol sérico < 200 mg/dL, y eran mujeres no fumadoras, no grávidas y no lactantes, no usuarias de alopurinol y probucol, con hipertensos sometidos a medicación antihipertensiva. Todos los individuos fueron sometidos a un período preparatorio de cuatro semanas sin alcohol, suplementos vitamínicos, dexametasona y paracetamol. RESULTADOS: Niveles reducidos de CAT (p = 0,013), GSH (p = 0,003) y MDA (p = 0,014), y altos niveles de GPx (p = 0,001) y ceruloplasmina (p = 0,015) fueron obtenidos en el grupo de hipertensos, en comparación con los controles. Fue obtenida una correlación positiva entre la presión sistólica y el MDA en la presión de hipertensos y diastólica y CAT en los controles. CONCLUSIÓN: Los datos obtenidos son sugestivos de que los hipertensos presentaban desequilibrio en reacciones de reducción y oxidación, a despecho del posible efecto atenuante de su medicación antihipertensiva.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antioxidantes/análise , Hipertensão/sangue , Estresse Oxidativo/fisiologia , Anti-Hipertensivos/uso terapêutico , Antioxidantes/metabolismo , Brasil , Biomarcadores/sangue , Catalase/sangue , Métodos Epidemiológicos , Glutationa/sangue , Hipertensão/tratamento farmacológico , Malondialdeído/sangue , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
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