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1.
Sci Rep ; 7: 46051, 2017 04 11.
Article in English | MEDLINE | ID: mdl-28397867

ABSTRACT

There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent hypertension yet remain largely unexplored. Here, we tested the role of oxidative state as an essential factor along with high salt and fructose treatment in causing hypertension. Fischer male rats were supplemented with a high-fructose diet (20% in water) for 20 weeks and maintained on high-salt diet (8%) associate in the last 10 weeks. Fructose-fed rats exhibited a salt-dependent hypertension accompanied by decrease in renal superoxide dismutase activity, which is the first footprint of antioxidant inactivation by reactive oxygen species (ROS). Metabolic changes and the hypertensive effect of the combined fructose-salt diet (20 weeks) were markedly reversed by a superoxide scavenger, Tempol (10 mg/kg, gavage); moreover, Tempol (50 mM) potentially reduced ROS production and abolished nuclear factor-kappa B (NF-κB) activation in human embryonic kidney HEK293 cells incubated with L-fructose (30 mM) and NaCl (500 mosmol/kg added). Taken together, our data suggested a possible role of oxygen radicals and ROS-induced activation of NF-κB in the fructose- and salt-induced hypertension associated with the progression of the renal disease.


Subject(s)
Fructose/adverse effects , Hypertension/metabolism , Hypertension/pathology , NF-kappa B/metabolism , Oxidative Stress , Sodium Chloride/adverse effects , Antioxidants/metabolism , Blood Pressure , Body Weight , Cyclic N-Oxides/pharmacology , Diet , Drinking Behavior , Feeding Behavior , Gene Expression Regulation/drug effects , Glucose Tolerance Test , HEK293 Cells , Humans , Hypertension/blood , Hypertension/physiopathology , Kidney/drug effects , Kidney/enzymology , Kidney/pathology , Lymphocytes/drug effects , Lymphocytes/metabolism , Monocytes/drug effects , Monocytes/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Spin Labels , Superoxide Dismutase/metabolism
2.
Adv Nutr ; 6(6): 729-37, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26567197

ABSTRACT

Although fructose consumption has dramatically increased and is suspected to be causally linked to metabolic abnormalities, the mechanisms involved are still only partially understood. We discuss the available data and investigate the effects of dietary fructose on risk factors associated with metabolic disorders. The evidence suggests that fructose may be a predisposing cause in the development of insulin resistance in association with the induction of hypertriglyceridemia. Experiments in animals have shown this relation when they are fed diets very high in fructose or sucrose, and human studies also show this relation, although with conflicting results due to the heterogeneity of the studies. The link between increased fructose consumption and increases in uric acid also has been confirmed as a potential risk factor for metabolic syndrome, and insulin resistance/hyperinsulinemia may be causally related to the development of hypertension. Collectively, these results suggest a link between high fructose intake and insulin resistance, although future studies must be of reasonable duration, use defined populations, and improve comparisons regarding the effects of relevant doses of nutrients on specific endpoints to fully understand the effect of fructose intake in the absence of potential confounding factors.


Subject(s)
Dietary Sucrose/administration & dosage , Fructose/administration & dosage , Fructose/adverse effects , Metabolic Diseases/etiology , Animals , Diet , Fructose/metabolism , Humans , Hypertension/etiology , Hypertriglyceridemia/etiology , Insulin/blood , Insulin Resistance , Lipid Metabolism , Mice , Obesity/etiology , Rats , Risk Factors , Uric Acid/blood , Weight Gain
3.
J Hypertens ; 33(1): 14-23, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25380160

ABSTRACT

OBJECTIVE: Considering the growing body of evidence that indicates the contribution of superoxide anions (O2) and other reactive oxygen species (ROS) to the development of hypertension, we assessed whether animal models of hypertension have a benefic effect with tempol, a superoxide dismutase mimetic, to help augment the design of future studies. METHODS: Studies published between July 1998 and December 2012 on blood pressure (BP) in different hypertensive models were obtained after an electronic and manual search of PubMed. In-depth analyses of the methodological quality of the studies and the mean arterial pressure (MAP) changes after treatment with tempol were performed, as well as the subgroup analyses on the route of tempol delivery. RESULTS: Out of the 144 identified studies, 28 were included after screening. The data showed that tempol reduced MAP by computing the standardized mean difference with the value of 4.622 (95% confidence interval 3.24-5.99). The quality of studies included in the meta-analysis was category II; however, omission of details in the trials might have biased the results. There was substantial heterogeneity in the results with an I of 94.45%, which persisted after stratifying for the route of tempol delivery. CONCLUSION: In conclusion, this analysis shows that antioxidant treatment with tempol can reduce BP, suggesting that ROS plays a role in the pathogenesis of increased BP in the hypertension models used in the current research practice.


Subject(s)
Antioxidants/therapeutic use , Biomimetic Materials/therapeutic use , Cyclic N-Oxides/therapeutic use , Hypertension/drug therapy , Superoxide Dismutase/therapeutic use , Animals , Biomimetic Materials/pharmacology , Blood Pressure/drug effects , Blood Pressure/physiology , Cyclic N-Oxides/pharmacology , Disease Models, Animal , Hypertension/metabolism , Rats , Spin Labels , Superoxide Dismutase/pharmacology , Superoxides/metabolism
4.
Biometals ; 27(2): 349-61, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24549594

ABSTRACT

Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of diabetes. We tested the hypothesis that oxidative stress is involved in the severity of the tissues injury when iron supplementation is administered in a model of type 1 diabetes. Streptozotocin (Stz)-induced diabetic and non-diabetic Fischer rats were maintained with or without a treatment consisting of iron dextran ip at 0.1 mL day(-1) doses administered for 4 days at intervals of 5 days. After 3 weeks, an extensive increase (p < 0.001) in the production of reactive oxygen species (ROS) in neutrophils of the diabetic animals on iron overload was observed. Histological analysis revealed that this treatment also resulted in higher (p < 0.05) tissue iron deposits, a higher (p < 0.001) number of inflammatory cells in the pancreas, and apparent cardiac fibrosis, as shown by an increase (p < 0.05) in type III collagen levels, which result in dysfunctional myocardial. Carbonyl protein modification, a marker of oxidative stress, was consistently higher (p < 0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlation was found between ROS production and iron pancreas stores (r = 0.42, p < 0.04), iron heart stores (r = 0.54, p < 0.04), and change of the carbonyl protein content in pancreas (r = 0.49, p < 0.009), and heart (r = 0.48, p < 0.02). A negative correlation was still found between ROS production and total glutathione content in pancreas (r = -0.50, p < 0.03) and heart (r = -0.45, p < 0.04). In conclusion, our results suggest that amplified toxicity in pancreatic and cardiac tissues in rats with diabetes on iron overload might be attributed to increased oxidative stress.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/pathology , Disease Models, Animal , Iron-Dextran Complex/toxicity , Oxidative Stress/drug effects , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 1/chemically induced , Iron Overload/chemically induced , Iron Overload/complications , Iron Overload/metabolism , Iron-Dextran Complex/administration & dosage , Iron-Dextran Complex/pharmacokinetics , Male , Rats , Rats, Inbred F344 , Reactive Oxygen Species/metabolism , Streptozocin , Tissue Distribution
5.
J Biosci ; 36(4): 731-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21857120

ABSTRACT

Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.


Subject(s)
Disease Models, Animal , Hypertension, Renal/physiopathology , Hypertension/physiopathology , Models, Animal , Rats , Animals , Denervation/adverse effects , Diet/adverse effects , Humans , Hypertension/etiology , Hypertension/genetics , Hypertension, Renal/etiology , Hypertension, Renal/genetics , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Pressoreceptors/surgery , Rats, Inbred Dahl , Rats, Inbred SHR , Rats, Transgenic
6.
Arq. ciências saúde UNIPAR ; 15(1)jan.-abr. 2011. tab
Article in Portuguese | LILACS | ID: lil-621345

ABSTRACT

Um estilo de vida sedentário deve ser considerado um importante fator de risco capaz de ser modificado para indivíduos com diabetes mellitus (DM) tipo 2, já que atividade física regular oferece múltiplos benefícios que incluem melhora da sensibilidade à insulina e do controle glicêmico, aumento do condicionamento cardiorespiratório e redução do risco de mortalidade cardiovascular. Entretanto, o estabelecimento de programas de treinamentos e de guias práticos para o manejo adequado na diabetes tipo 2 não têm sido sugeridos num consenso único. Dessa forma, o presente estudo selecionou publicações realizadas a partir de dados Pubmed, objetivando discutir informações que estão sendo descritas na literatura de forma a reforçar bases que representem uma resposta adaptativa às demandas do treinamento, apoiando uma positiva função da atividade física no cuidado da diabetes tipo 2.


A sedentary lifestyle should be considered an important modifiable risk factor for individuals with type 2 diabetes mellitus (DM) already that regular physical activity offers many benefits including improved insulin sensitivity and glycemic control, increased cardiorespiratory fitness and reduced risk of cardiovascular mortality. However, the establishment of training programs and practical guidelines for management of type 2 diabetes has not been suggested in a single consensus. Thus, this study through of the selection of publications was performed on Pubmed aims to discuss the data being reported in the literature in order to reinforce the base that represent an adaptative response to the demands of training, supporting a positive role of physical activity in the management of type 2 diabetes.


Subject(s)
Humans , Blood Glucose , Diet Therapy , Insulin , Motor Activity , Physical Education and Training
7.
Arq Bras Cardiol ; 95(2): 272-8, 2010 Aug.
Article in English, Portuguese | MEDLINE | ID: mdl-20857052

ABSTRACT

Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.


Subject(s)
Atherosclerosis/etiology , Cholesterol, Dietary/adverse effects , Disease Models, Animal , Hypercholesterolemia/complications , Animals , Atherosclerosis/pathology , Cholesterol/blood , Cholesterol, Dietary/administration & dosage , Coronary Vessels/pathology , Diet , Diet, Atherogenic , Endothelium, Vascular/pathology , Endothelium, Vascular/physiopathology , Hypercholesterolemia/metabolism , Rabbits
8.
Arq. bras. cardiol ; 95(2): 272-278, ago. 2010. ilus
Article in Portuguese | LILACS | ID: lil-557820

ABSTRACT

Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.


Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.


Subject(s)
Animals , Rabbits , Atherosclerosis/etiology , Cholesterol, Dietary/adverse effects , Disease Models, Animal , Hypercholesterolemia/complications , Atherosclerosis/pathology , Cholesterol, Dietary/administration & dosage , Cholesterol/blood , Coronary Vessels/pathology , Diet , Diet, Atherogenic , Endothelium, Vascular/pathology , Endothelium, Vascular/physiopathology , Hypercholesterolemia/metabolism
9.
Rev. bras. anal. clin ; 42(1): 49-54, 2010. ilus, tab
Article in Portuguese | LILACS | ID: lil-550549

ABSTRACT

Dentre as enfermidades pertencentes ao grupo das doenças cardiovasculares, a aterosclerose têm sido, atualmente, considerada problema de saúde pública no Brasil. tendo em vista o seu papel no perfil de mortalidade e das alterações tatológicas que acarretam. Pesquisas têm demonstrado associações entre o consumo de gordura saturada, nível de coleterol e doenças coronárias, no entanto, medidas dietéticas isoladas mostram-se, frqquentemente, insuficientes, tornando-se necessária à associação dessas com fármacos hipolipidêmicos capazes de reduzir a síntese endógena de colesterol ou melhorar a eficiência de sua remoção do plasma. Durante os últimos anos, um número crescente de estudos tem relacionado flavonóides a promissores fármacos naturais, uma vez que têm sido atribuidos a esses a capacidade de modificar a biossíntese de eicosanóides (resposta anti-prostanóide e antiinflamatória), proteger colesterol LDL da oxidação (inibindo formação de placa aterosclerótica), prevenir agregação plaquetária (efeitos anti-trombóticos) e promover relaxamento de músculo liso (efeito anti-hipertensivo e anti-isquêmico). Sendo assim, essa revisão sugere que a proteção contra doenças cardiovasculares associadas por meio de dietas ricas em flavonóides pode resultar em uma variedade de efeitos produzidos por diferentes mecanismos, necessitando, portanto, de maiores investigações e entendimewntos científicos.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Cholesterol , Flavonoids
10.
Rev. bras. farmacogn ; 19(2a): 488-500, Apr.-June 2009. tab
Article in English | LILACS | ID: lil-524558

ABSTRACT

Diabetes mellitus (DM) é uma doença metabólica crônica caracterizada por hipeglicemia que tem impacto significante em seus pacientes. Sua incidência está crescendo rapidamente conduzindo para aumento no custo dos cuidados da doença e de suas complicações. O tratamento envolve, além de controle dietético e atividade física, o uso de fármacos que ocasionam efeitos colaterais para atingir ações farmacológicas desejadas. Entretanto, produtos de plantas são, freqüentemente, considerados menos tóxicos e com menos efeitos colaterais que drogas sintéticas e amplamente utilizadas pela população. Nesse trabalho várias espécies de plantas utilizadas experimentalmente ou na medicina popular, agindo de diferentes formas de modo a controlar glicemia e/ou inibir sintomas e complicações características da diabetes serão revisadas para avaliação de seus supostos efeitos terapêuticos.


Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemy that has a significant impact for their patients. Its incidence is raising leading to an increase in the cost of the cares of the disease and of its complications. The treatment involves, besides dietary control and physical activity, the use of drugs that cause side effects to reach wanted pharmacological actions. However, products of plants are, frequently, considered less poisonous and with fewer side effects than synthetic drugs and widely used by the population. In this paper, several species of plants, used experimentally or in the popular medicine, acting by different ways to control glycemia and/or to inhibit symptoms and characteristic complications of the diabetes, they will be reviewed for evaluation of their supposed therapeutic effects.

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