Waleska Claudia Amaral Dornas

Animal models for the study of arterial hypertension.

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.

Experimental atherosclerosis in rabbits

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.

Health Implications of High-Fructose Intake and Current Research

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.

Oxidative stress causes hypertension and activation of nuclear factor-κB after high-fructose and salt treatments

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.

High dietary salt decreases antioxidant defenses in the liver of fructose-fed insulin-resistant rats

In this study we investigated the hypothesis that a high-salt diet to hyperinsulinemic rats might impair antioxidant defense owing to its involvement in the activation of sodium reabsorption to lead to higher oxidative stress. Rats were fed a standard (CON), a high-salt (HS), or a high-fructose (HF) diet for 10 weeks after which, 50% of the animals belonging to the HF group were switched to a regimen of high-fructose and high-salt diet (HFS) for 10 more weeks, while the other groups were fed with their respective diets. Animals were then euthanized and their blood and liver were examined. Fasting plasma glucose was found to be significantly higher (approximately 50%) in fructose-fed rats than in the control and HS rats, whereas fat liver also differed in these animals, producing steatosis. Feeding fructose-fed rats with the high-salt diet triggered hyperinsulinemia and lowered insulin sensitivity, which led to increased levels of serum sodium compared to the HS group. This resulted in membrane perturbation, which in the presence of steatosis potentially enhanced hepatic lipid peroxidation, thereby decreasing the level of antioxidant defenses, as shown by GSH/GSSG ratio (HFS rats, 7.098±2.1 versus CON rats, 13.2±6.1) and superoxide dismutase (HFS rats, 2.1±0.05 versus CON rats, 2.3±0.1%), and catalase (HFS rats, 526.6±88.6 versus CON rats, 745.8±228.7 U/mg ptn) activities. Our results indicate that consumption of a salt-rich diet by insulin-resistant rats may lead to regulation of sodium reabsorption, worsening hepatic lipid peroxidation associated with impaired antioxidant defenses.

Efeitos antidiabéticos de plantas medicinais

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.

Salt overload in fructose-fed insulin-resistant rats decreases paraoxonase-1 activity

Paraoxonase 1 (PON1) is a HDL-associated esterase/lactonase and its activity is inversely related to the risk of cardiovascular diseases. The aim of the present study was to evaluate the effect of a high-salt diet on serum PON1 activity in fructose-fed insulin-resistant rats. Adult male Fischer rats were initially divided into two groups. Control (CON), which received a normal salt diet and drinking water throughout the study; high fructose (HF), which received a normal salt diet and 20% fructose supplemented drinking water. After 10 weeks, half of the animals from HF group were randomly switched to a high-salt diet and 20% fructose supplemented drinking water (HFS) for more 10 weeks. Serum PON1 activity was determined by synthetic substrate phenyl acetate. HFS rats showed markedly decreased PON1 activity (HFS rats, 44.3 ± 14.4 g/dL versus CON rats, 64.4 ± 13.3 g/dL, P < 0.05) as compared to controls. In parallel, the level of oxidative stress, as indicated by thiobarbituric acid reactive substances (TBARS), was increased in HFS rats by 1.2-fold in the liver in relation to controls and was negatively correlated with PON activity. Differential leukocyte counts in blood showed a significant change in lymphocytes and monocytes profile. In conclusion, these results show that PON1 activity is decreased in fructose-fed insulin-resistant rats on a high-salt diet, which may be associated with increased oxidative stress, leading to inflammation.