The use of fructose as a sweetener. Is it a safe alternative for our immune system?

Fructose is a constituent of sucrose and other polymers referred to as inulin or fructans. We can find in cereals, vegetables, and honey. It has the property of being 1.5 times sweeter than sucrose. Our objective was to test this sweetener under and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. For this purpose, we made use of lymphocyte cultures and the analysis of their CD4+ and CD8+ subpopulations. Computational methods propose the mechanism of action. Our data showed a reduction in all lymphocyte subfractions evaluated, resulting in a reduction in total lymphocytes, as well as an increase in the DNA damage of cells exposed to fructose. It was possible to propose that fructose modulates gene expression, mainly interfering with the MAPK8, APTX, TUBGCP3, and LST1 genes. Although fructose is used globally as a sweetener, its use should be cautious, as our study points out that it has cytotoxic and genotoxic effects. PRACTICAL APPLICATIONS: Fructose is one of the most sold and used sweeteners in the world. We show here that its use must be restricted and used carefully because it can alter the gene expression and also interfere with cellular and genetic metabolism and may even interfere with the immune response.

Steviol, the active principle of the stevia sweetener, causes a reduction of the cells of the immunological system even consumed in low concentrations.

AIM: Steviol is a natural diterpenoid glycoside isolated from Stevia rebaudiana Bertoni leaves and widely used as a non-caloric sweetener. In addition to their sweet taste, Steviol glycosides may also have some therapeutic benefits. There are few reports on the cytotoxicity of Steviol in human cells. Our objective was to test this sweetener under and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. METHODS: For this purpose, we made use of lymphocyte cultures and the analysis of their CD3+, CD4+, and CD8+ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. RESULTS AND CONCLUSION: Our results showed that Steviol reduces the number of lymphocytes due to falls of CD4+, CD8+, and CD4+CD8+ subpopulations. Besides, we observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that Steviol modulates gene expression, mainly interfering with the SESN1, NAP1L1, SOX4, and TREX1 genes. Although Steviol is used globally as a sweetener, its use should be cautious, as our study points out that Steviol has cytotoxic, genotoxic and mutagenic effects in the concentrations and conditions tested in the culture of human lymphocyte cells.

Rat postnatal prostate development is impaired by in vitro high-glucose environment.

The prostate development has an important postnatal period where cell proliferation begins at the first days after birth and is related to gland growth and ramification. Any metabolic and/or hormonal changes occurring during the postnatal period can interfere with prostate branching. Hyperglycemia is a common condition in low-weight preterm babies at neonatal period and also a disorder found in the offspring of obese mothers. Thus, this study aimed to investigate the in vitro effects of a glucose-rich environment during prostate postnatal development. Wistar rats prostate were removed at birth and cultured for 1, 2 and 3 days in DMEM under normal (5.5 mM) or elevated (7 and 25 mM) glucose concentrations. Samples were processed for morphological analysis, PCNA and smooth muscle α-actin immunohistochemistry, evaluation of active caspase-3, ERK1/2 and Wnt5a gene expression. High glucose concentrations reduced the number of prostatic buds and proliferating cells. The natural increase in smooth muscle cells and collagen deposition observed in control prostates during the first 3 days of development was reduced by elevated glucose concentrations. The amount of active caspase-3 was higher in prostates incubated at 7 mM and TGF-ß levels also increased sharply after both glucose concentrations. Additionally, high glucose environment decreased ERK 1/2 activation and increased Wnt5a expression. These data show that high levels of glucose during the first postnatal days affected prostate development by inhibiting cell proliferation which impairs bud branching and this was associated with anti-proliferative signals such as decreased ERK1/2 activation and increased Wnt5a expression.

Metabolic syndrome accentuates post-traumatic stress disorder-like symptoms and glial activation.

The relationship between individuals with post-traumatic stress disorder (PTSD) and the development of metabolic syndrome (MS) is well understood, but the relationship between individuals with preexisting MS and the development of PTSD is not yet known. Therefore, we evaluated the course of PTSD development in preexisting MS rats and we quantified the glial fibrillary acidic protein (GFAP) and ionized the calcium binding adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental animals. Male Wistar rats were divided into two groups: control or 10 % fructose for 5 weeks. After 5 weeks of MS induction, a group of animals was used to characterize MS. In another group, after 5 weeks of MS induction, animals were exposed to or not exposed to inescapable footshocks, followed by social isolation. After 14 days of a retention interval, the animals were re-exposed to the inescapable footshocks box, and the freezing time was evaluated. Over the following days, the animals were tested using the open field, social interaction and forced swimming tests, respectively. In another group of animals, after induction of MS and PTSD as previously described, elevated plus maze and object recognition tests were performed. Our results demonstrate that fructose solution for 5 weeks was able to induce MS, and animals with MS had more pronounced PTSD-like symptoms and a greater increase in GFAP and Iba-1 in the hippocampus and prefrontal cortex. In conclusion, MS accentuated PTSD-like symptoms that may be related to increased glial activation. This study helps reveal factors that may predispose individuals to the development of PTSD, such as metabolic disorders.

Cd36 gene expression in adipose and hepatic tissue mediates the lipids accumulation in liver of obese rats with sucrose-induced hepatic steatosis.

Obesity is considered a global epidemic and is mainly associated with the development of diabetes, cardiovascular diseases and Non-Alcoholic Fatty Liver (NAFLD). The pathogenesis between obesity and hepatic steatosis is partially known, but could involve differentiated or tissue-specific participation of the expression of Cd36 mRNA that codes for a receptor which is a transporter of free fatty acids (FFA) in different tissues, favoring the lipids storage. This relative expression was evaluated in adipose and liver tissue in rats with steatosis after consumption of sucrose for 30 and 40 weeks. Ten Wistar rats were divided into two experimental groups (St-30 and St-40), which received a standard diet plus 30 % sucrose in their water intake. These rats showed a significant increase in abdominal fat, serum biochemical determinations, HOMA-IR; as well as, changes in adipocytes size and mild portal hepatitis and grade 2 hepatic steatosis. The relative expression of Cd36 mRNA increased in liver tissue after 30 (4.5-fold) and 40 (8.5-fold) weeks of sucrose ingestión but no in adipose tissue; with respect to control group (P < 0.05). This expression was associated with a significant increase in the levles of sCD36 in serum, which is indicator of the presence of the FFA transporter in the hepatocyte membrane causing lipids accumulation. The above shows the link between the adipose and hepatic tissue for the accumulation of steatotic fat in the liver through time, mediated by the relative expression of cd36 mRNA that encodes for the FFA transporter.

Aerobic exercise modulates cardiac NAD(P)H oxidase and the NRF2/KEAP1 pathway in a mouse model of chronic fructose consumption.

The present study investigated the effects of exercise on the cardiac nuclear factor (erythroid-derived 2) factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway in an experimental model of chronic fructose consumption. Male C57BL/6 mice were assigned to Control, Fructose (20% fructose in drinking water), Exercise (treadmill exercise at moderate intensity), and Fructose + Exercise groups (n = 10). After 12 wk, the energy intake and body weight in the groups were similar. Maximum exercise testing, resting energy expenditure, resting oxygen consumption, and carbon dioxide production increased in the exercise groups (Exercise and Fructose + Exercise vs. Control and Fructose groups, P < 0.05). Chronic fructose intake induced circulating hypercholesterolemia, hypertriglyceridemia, and hyperleptinemia and increased white adipose tissue depots, with no changes in blood pressure. This metabolic environment increased circulating IL-6, IL-1ß, IL-10, cardiac hypertrophy, and cardiac NF-κB-p65 and TNF-α expression, which were reduced by exercise (P < 0.05). Cardiac ANG II type 1 receptor and NAD(P)H oxidase 2 (NOX2) were increased by fructose intake and exercise decreased this response (P < 0.05). Exercise increased the cardiac expression of the NRF2-to-KEAP1 ratio and phase II antioxidants in fructose-fed mice (P < 0.05). NOX4, glutathione reductase, and catalase protein expression were similar between the groups. These findings suggest that exercise confers modulatory cardiac effects, improving antioxidant defenses through the NRF2/KEAP1 pathway and decreasing oxidative stress, representing a potential nonpharmacological approach to protect against fructose-induced cardiometabolic diseases.NEW & NOTEWORTHY This is the first study to evaluate the cardiac modulation of NAD(P)H oxidase (NOX), the NRF2/Kelch-like ECH-associated protein 1 pathway (KEAP), and the thioredoxin (TRX1) system through exercise in the presence of moderate fructose intake. We demonstrated a novel mechanism by which exercise improves cardiac antioxidant defenses in an experimental model of chronic fructose intake, which involves NRF2-to-KEAP1 ratio modulation, enhancing the local phase II antioxidants hemoxygenase-1, thioredoxin reductase (TXNRD1), and peroxiredoxin1B (PDRX1), and inhibiting cardiac NOX2 overexpression.

Alterations to DNA, apoptosis and oxidative damage induced by sucralose in blood cells of Cyprinus carpio.

Sucralose (SUC) is an organochlorine that is used as a common sweetener in different dietary products around the world. Its extended use and production have led to this product is released into the environment in concentrations ranging from ng L-1 to µg L-1 in surface waters, groundwaters, wastewater treatment plants and ocean waters. A previous study carried out by our research team demonstrated that SUC is capable of inducing oxidative stress in Cyprinus carpio at environmentally-relevant concentrations. The aim of this study was to evaluate if SUC was capable of inducing alterations to DNA, apoptosis, and oxidative damage in the blood cells of C. carpio. Carps were exposed to two environmentally-relevant concentrations (0.05 and 155 µg L-1) of SUC, and the following biomarkers were determined: comet assay, micronucleus test (MN), caspase-3 activity, TUNEL assay, hydroperoxide content, lipid peroxidation level, protein carbonyl content and superoxide dismutase and catalase activities. Results obtained showed that SUC is capable of inducing DNA damage. A maximum increase of 35% and 23% were observed for c1 and c2, respectively in the comet assay; increases of 586% and 507.7% for c1 and c2, respectively, were found at 72 h through the MN test. The activity of caspase-3 showed a greater response for c1 and c2 at 96 h, with 271% and 493.5%, respectively. TUNEL assay also showed the highest response at 96 h, with 51.8 for c1 and 72.9 for c2; c1 y c2 were able to induce oxidative stress with the highest expression at 72 h. A correlation between DNA damage biomarkers, apoptosis and plasma levels of SUC in both concentrations were observed. With the data obtained, we can conclude that SUC, at environmentally-relevant concentrations, was capable of generating DNA alterations, apoptosis and oxidative stress in blood cells in common carp.

Astrogliosis and decreased neural viability as consequences of early consumption of aspartame and acesulfame potassium in male Wistar rats.

Artificial sweeteners are mainly used as substitutes for sucrose derivates. In this study, we analyzed if the chronic consumption of aspartame or acesulfame potassium at an early age, produces histological alterations, astrogliosis and decreased neuronal viability, in hippocampus, prefrontal cortex, amygdala and hypothalamus of male Wistar rats. A histological analysis was performed on male Wistar rats that consumed aspartame or acesulfame potassium during 90 days, initiating the consumption of sweeteners immediately after weaning. The evaluation of neuronal morphology in different areas of the brain was performed with hematoxylin - eosin staining. To measure astrogliosis and neuronal viability, we used the immunohistochemical technique, with the glial fibrillary acidic protein immunomodulators (GFAP) and with neuronal-specific enolase (NSE). The consumption of aspartame or acesulfame potassium promoted morphological changes of neurons including increased pyknotic nuclei and vacuolization in all the brain areas studied. In hippocampus, prefrontal cortex, amygdala and hypothalamus, astrogliosis and reduction of neural viability were observed in sweeteners consumers in comparison with the control group. Chronic consumption of ASP and ACK from early stages of development and during long periods, may promote neural modifications, astrogliosis and decrease neuronal viability in prefrontal cortex, amygdala, hippocampus, and hypothalamus.

Sickness behavior is accentuated in rats with metabolic disorders induced by a fructose diet.

This study investigated behavioral responses to an immune challenge among animals with fructose-induced metabolic disorders. Adult male Wistar rats were provided either water or a fructose solution (10%) for 5 weeks. Sickness behaviors were assessed 2h following the injection of either a lipopolysaccharide (LPS) or vehicle. The rats were subjected to an open field test, a social interaction test, a food intake test and a fever evaluation. Cytokine expression was assessed in both adipose tissue and hypothalamus samples. The neural response was assessed in the forebrain immunohistochemistry for c-Fos. Compared with the control group, the fructose diet induced dyslipidemia and significantly higher plasma total cholesterol, HDL-cholesterol, triglyceride, and glucose levels as well as both epididymal and retroperitoneal adiposity. Furthermore, in response to LPS (1 mg/kg), the rats subjected to a fructose diet exhibited exacerbated sickness behaviors and accentuated febrile responses. LPS induced Fos protein expression in several areas of the brains of the control rats; however, higher numbers of Fos-positive cells were observed in the brains of the rats that were fed a fructose diet. Moreover, larger increases in cytokine expression were observed in both the hypothalamus and the adipose tissue of the obese rats compared with the control rats in response to LPS. In this study, fructose diets played an important role in both the induction of metabolic disorders and the modulation of sickness behaviors in response to an immunological challenge, most likely through the induction of cytokines in the hypothalamus.

Efeitos dos diferentes tipos de adoçantes dietéticos isolados nos parâmetros nutricionais e bioquímicos de ratos / Effects of different types of isolated dietary sweeteners on nutritional and biochemical parameters of rats

OBJECTIVE: This study aimed to evaluate the effects of using different types of isolated sweeteners in nutritional and biochemical parameters of rats. METHODS: We used 36 adult male rats, maintained on diet for 42 days and divided into six groups: Group C - Control, Group AS - Aspartame; Group ES - Stevia; Group SU - Sucralose; Group CI - Cyclamate; group SA - Saccharin. The animals were fed a standard AIN 93M with replacement of sucrose by its sweetener and water ad libitum. The animals were kept in metabolic cages in a controlled environment and were recorded body weight, food and water consumption, urinary and fecal excretion. At the end of the study the animals were anaesthetized intraperitoneally with a combination of ketamine, hydrochloride xylazine and acepromazine and euthanized by cardiac puncture. Theserum was used to determine glucose, lipid, liver and kidney profiles. RESULTS: Animals receiving sweeteners had lower food intake compared to Group C, highlighting the SA Group. The results indicated that the sweeteners used in this study and the maximum proportion suggested by ANVISA, particularly saccharin, stevia, sucralose and cyclamate, decreased the animals food intake. Sweeteners did not influence the other study variables. CONCLUSIONS: The sweeteners reduced food intake, but no change was noticed in the animal's final weight gain and other variables. We suggest additional long term research

OBJETIVO: Avaliar os efeitos do uso de diferentes tipos de adoçantes isolados nos parâmetros nutricionais e bioquímicos de ratos. MÉTODOS: Foram utilizados 36 ratos machos, Wistar, adultos, mantidos sob dieta durante 42 dias e distribuídos em seis Grupos: Grupo C ­ Controle; Grupo AS ­ Aspartame; Grupo ES ­ Estévia; Grupo SU ­ Sucralose; Grupo CI ­ Ciclamato; Grupo SA ­ Sacarina. Os animais receberam dieta padrão AIN 93M com substituição da sacarose pelo respectivo adoçante e amido, com água ad libitum. Os animais foram mantidos em ambiente controlado e foram registrados peso corporal, consumo alimentar e hídrico, excreção urinária e fecal. Os animais foram anestesiados via intraperitoneal, com Cloridrato de Cetamina, Cloridrato de Xilazina e Acepromazina. A eutanásia foi realizada por punção cardíaca. O soro foi utilizado para determinar perfil glicídico, lipídico, hepático e renal. RESULTADOS: Os animais que receberam adoçante apresentara menor consumo alimentar em relação ao Grupo C, destacando-se o Grupo SA. Os resultados indicaram que os adoçantes utilizados no presente estudo e na proporção máxima sugerida pela ANVISA, principalmente sacarina, estévia, sucralose e ciclamato, diminuíram o consumo alimentar dos animais. Os adoçantes não influenciaram as demais variáveis do estudo. CONCLUSÕES: Os adoçantes reduziram o consumo alimentar, porém sem alteração no ganho de peso final dos animais e nas demais variáveis estudadas. Sugere-se a realização de pesquisas adicionais em longo prazo

Excess fructose intake-induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals.

We studied the effect of feeding normal adult male rats with a commercial diet supplemented with fructose added to the drinking water (10% w/v; fructose-rich diet, FRD) on the adipogenic capacity of stromal-vascular fraction (SVF) cells isolated from visceral adipose tissue (VAT) pads. Animals received either the commercial diet or FRD ad libitum for 3 weeks; thereafter, we evaluated the in vitro proliferative and adipogenic capacities of their VAT SVF cells. FRD significantly increased plasma insulin, triglyceride and leptin levels, VAT mass/cell size, and the in vitro adipogenic capacity of SVF cells. Flow cytometry studies indicated that the VAT precursor cell population number did not differ between groups; however, the accelerated adipogenic process could result from an imbalance between endogenous pro- and anti-adipogenic SVF cell signals, which are clearly shifted towards the former. The increased insulin milieu and its intracellular mediator (insulin receptor substrate-1) in VAT pads, as well as the enhanced SVF cell expression of Zpf423 and peroxisome proliferator receptor-γ2 (all pro-adipogenic modulators), together with a decreased SVF cell concentration of anti-adipogenic factors (pre-adipocyte factor-1 and wingless-type MMTV-10b), strongly supports this assumption. We hypothesize that the VAT mass expansion recorded in FRD rats results from the combination of initial accelerated adipogenesis and final cell hypertrophy. It remains to be determined whether FRD administration over longer periods could perpetuate both processes, or whether cell hypertrophy itself remains responsible for a further VAT mass expansion, as observed in advanced/morbid obesity.

Efficacy and safety of two analogs of L-carnitine on rats made insulin resistant by a high-fructose diet.

AIM: To evaluate the efficacy and safety of 2 analogs of L-carnitine on rats made insulin resistant by a high-fructose diet. METHODS: Using rats made insulin resistant by a high-fructose diet, we investigated the impact of 2 analogs of L-carnitine (25 mg/kg) and L-carnitine (250 mg/kg) on glucose, triglycerides and cholesterol blood levels, and liver glycogen. We also evaluated the safety of both analogs by the assessment of some biochemical and hematological parameters, a histological analysis and a study of embryotoxicity. RESULTS: Both analogs reduced the levels of triglycerides in the liver and plasma, but only analog 2 reduced the cholesterol levels in insulin-resistant rats. No changes were observed in glycogen content. Safety evaluations revealed alterations in blood lymphocytes and embryotoxicity data. CONCLUSION: This study demonstrated that the 2 analogs maintain the pharmacological properties of L-carnitine but have a different efficacy, potency and toxicity.

Overview: the history, technical function and safety of rebaudioside A, a naturally occurring steviol glycoside, for use in food and beverages.

Rebaudioside A is a sweet tasting steviol glycoside extracted and purified from Stevia rebaudiana (Bertoni). Steviol glycosides can currently be used as a food ingredient in only a handful of countries. Questions on specifications, safety and special population effects have prevented steviol glycosides from obtaining a legal status permitting their use as a sweetener in most countries. A set of papers reporting results of research studies and reviews has been compiled in this Supplement to definitively answer unresolved questions. Specifically, recently completed studies on the general and reproductive toxicity of rebaudioside A corroborate studies carried out with purified steviol glycosides demonstrating safety at high dietary intake levels. Comparative metabolism studies provide further affirmation of the common metabolic pathway for all steviol glycosides and the common metabolism between rats and humans. Finally, clinical studies provide further evidence that purified rebaudioside A has no effect on either blood pressure or glucose homeostasis. This paper summarizes the information used to conclude that high purity rebaudioside A (rebiana) produced to food-grade specifications and according to Good Manufacturing Practices is safe for human consumption under its intended conditions of use as a general purpose sweetener.

Effects of Aspartame on Maternal-Fetal and Placental Weights, Length of Umbilical Cord and Fetal Liver: A Kariometric Experimental Study / Efectos del Aspartame sobre el Peso Materno-Fetal y Placentario, Largo del Cordón Umbilical e Hígado Fetal: Un Estudio Cartométrico Experimental

Aspartame is a synthetic sweetener consumed by more than half the adult population in 75 countries. Their metabolites can be toxic, principally to the liver and retina, and there are few studies on the use of aspartame in gestation. Twenty pregnant rats were weighed and allocated randomly (n=5 per group) to receive 14 mg/kg aspartame or water by oral-gastric drip. Treated Tl: aspartame diluted in water at room temperature; Treated T2: aspartame diluted in water heated to 40° C; control Cl: water at room temperature; and control C2: water heated to 40° C. Placentas were weighed, umbilical cords measured and 1000 nuclei of fetal hepatocytes (250 from each group) were analyzed morphometrically utilizing the technique of kariometry, with application of the Mann-Whitney U-Test. There were reductions in mean placental and maternal-fetal weights, in umbilical-cord length, and the majority of kariometric parameters of the hepatocytes in the group treated with aspartame diluted in distilled water at room temperature. Reduction of placental and maternal-fetal weights occurred, shortening of the umbilical cord, and decrease in kariometric parameters in fetal hepatocyte nuclei after administration of aspartame diluted in distilled water at 40°C temperature. The use of aspartame during gestation can be prejudicial to the fetus.

El aspartame es un endulzante sintético consumido por más de la mitad de la población adulta, en 75 países. Sus metabolitos pueden ser tóxicos, principalmente en el hígado y retina y hay algunos estudios sobre el aspartame en el embarazo. Veinte ratas preñadas fueron pesadas y distribuidas aleatoriamente (n=5 por grupo) y recibieron 14 mg/Kg de aspartame o agua por vía oral- gástrica. Tratamiento 1: aspartame diluido en agua a temperatura ambiente; Tratamiento T2: aspartame diluido en agua tibia a 40 °C; control Cl: agua a temperatura ambiente, y control C2: agua tibia a 40° C. Las placentas fueron pesadas, el cordón umbilical medido y 1000 núcleos de hepatocitos fetales (250 de cada grupo) se analizaron morfométricamente utilizando la técnica de canometría con aplicación del Test U de Mann-Whitney U-Test. En el grupo tratado con aspartame diluido en agua a temperatura ambiente, hubo reducción en los pesos promedios de la placenta y materno-fetal, largo del cordón umbilical y en la mayoría de los parámetros cartométricos de los hepatocitos. Lo mismo ocurrió en el grupo tratado con aspartame diluido en agua a 40 °C. El uso del aspartame durante las gestación puede ser perjudicial para el feto.

Analysis of genotoxic potentiality of stevioside by comet assay.

Stevioside is a natural non-caloric sweetener extracted from Stevia rebaudiana (Bertoni) leaves. It has been widely used in many countries, including Japan, Korea, China, Brazil and Paraguay, either as a substitute for sucrose in beverages and foods or as a household sweetener. The aim of this work was to study its genotoxic potentiality in eukaryotic cells. Wistar rats were treated with stevioside solution (4mg/mL) through oral administration (ad libitum) and the DNA-induced damage was evaluated using the single cell gel electrophoresis (comet assay). The results showed that treatment with stevioside generates lesions in peripheral blood, liver, brain and spleen cells in different levels, the largest effect being in liver. Therefore, these undesired effects must be better understood, once the data present here point to possible stevioside mutagenic properties.

Biological effects of stevioside on the survival of Escherichia coli strains and plasmid DNA.

Stevioside is widely used daily in many countries as a non-caloric sugar substitute. Its sweetening power is higher than that of sucrose by approximately 250-300 times, being extensively employed as a household sweetener, or added to beverages and food products. The purpose of this study was to ascertain stevioside genotoxic and cytotoxic potentiality in different biological systems, as its use continues to increase. Agarose gel electrophoresis and bacterial transformation were employed to observe the occurrence of DNA lesions. In addition to these assays, Escherichia coli strains were incubated with stevioside so that their survival fractions could be obtained. Results show absence of genotoxic activity through electrophoresis and bacterial transformation assays and drop of survival fraction of E. coli strains deficient in rec A and nth genes, suggesting that stevioside (i) is cytotoxic; (ii) could need metabolization to present deleterious effects on cells; (iii) is capable of generating lesions in DNA and pathways as base excision repair, recombination and SOS system would be important to recover these lesions.

Chronic administration of resveratrol prevents biochemical cardiovascular changes in fructose-fed rats.

BACKGROUND: There seems to be a link between the cluster of risk factors known as insulin resistance syndrome with endothelial dysfunction. Resveratrol (3,4,5-trihydroxyestilbene) (RV), an antioxidant found in many components of the human diet, has been proposed as an effective agent in the prevention of several pathologic processes. This study examined the effect of chronic administration of RV on endothelial nitric oxide synthase (eNOS) activity in cardiovascular tissues and on plasma lipid peroxidation in fructose-fed rats (FFR), an experimental model of this syndrome. METHODS: Male Sprague Dawley rats were separated into four groups: Control, Control + RV, FFR, and FFR + RV (n = 8 in each group). The RV (10 mg/kg/d by gavage) and fructose (10% in drinking water) were administered for 45 days. Metabolic variables and systolic blood pressure (BP) were measured. The eNOS activity was estimated in the mesenteric arterial bed and cardiac tissue homogenates by conversion of (3)H-arginine to (3)H-citrulline. Lipid peroxidation was estimated through the measurement of plasmatic thiobarbituric acid-reactive substances (TBARS). RESULTS: The RV chronic treatment prevented the increase in systolic BP and cardiac hypertrophy, restored FFR mesenteric and cardiac eNOS activities, and decreased the elevated TBARS levels that characterize FFR, without an effect on other metabolic variables. CONCLUSIONS: In concert with other effects, the increase in eNOS activity may contribute to the protective properties attributed to RV and, thus, to its beneficial effects on the cardiovascular system. These results suggest that an adequate supplementation of RV might help to prevent or delay the occurrence of atherogenic cardiovascular diseases associated to insulin-resistant states.

Effects of a saccharin and cyclamate mixture on rat embryos.

Sodium saccharin (NaS) and calcium cyclamate (CaC) are artificial sweeteners widely used in food and drink. To evaluate their toxicological effects on preimplantation mammalian embryos, pregnant rats were gavaged with 1.65 mg NaS/kg bw + 3.85 mg CaC/kg bw (DI) or 6.6 mg NaS/kg bw + 15.4 mg CaC/kg bw (D2) on days 1, 2, 3 and 4 of pregnancy (positive vaginal smear = day 1). The female rats were killed on day 5 of the pregnancy (GD 5), maternal organs weighed, and the blastocysts collected, counted and evaluated for gross morphology, cell number and mitotic index. There was no alteration in maternal organ weights, but there was an increase of the cell number/embryo in the dams treated with that NaS + CaC mixtures (D1 = 37.20 +/- 7.96; D2 = 37.26 +/- 10.90) compared to control group (32.24 +/- 6.73). Embryos whose dams were exposed to NaS + CaC may have adapted for implantation into the uterus but more studies are needed to demonstrate this mechanism of action.

Sugar and sugar substitutes: How safe are they?

For many consumers today, artificial sweeteners represent one of the more welcome ingredients produced by the food technology industry. Given the universally recognized love affair that humans have for sugar, it is difficult to think that substantial numbers would be compelled to exclude it from their diet for health reasons if substitutes were not around.