Effects of Ethanolic Extract of Cynara cardunculus (Artichoke) Leaves on Neuroinflammatory and Neurochemical Parameters in a Diet-Induced Mice Obesity Model.

This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex, hippocampus, striatum, cerebral cortex and liver of high-fat diet-induced obese mice. Food intake, body weight, visceral fat weight, and liver weight were also evaluated. Male Swiss mice were divided into control (low-fat purified diet) and obese (high-fat purified diet) groups. After 6 weeks, mice were divided into control + saline, control + C. cardunculus leaf ethanol extract, obese + saline, obese + C. cardunculus leaf ethanol extract. Cynara cardunculus leaf ethanol extract (1600 mg/kg/day) or saline was administered orally for 4 weeks. Brain structures (hypothalamus, hippocampus, prefrontal cortex, striatum and cerebral cortex) and liver were removed. Treatment with C. cardunculus leaf ethanol extract did not affect body weight but did reduce visceral fat. Obesity can cause inflammation and oxidative stress and increase the activity of antioxidant enzymes in brain structures. Treatment with ethanolic extract of C. cardunculus leaves partially reversed the changes in inflammatory damage parameters and oxidative damage parameters and attenuated changes in the antioxidant defense. The C. cardunculus leaf ethanol extract benefited from the brains of obese animals by partially reversing the changes caused by the consumption of a high-fat diet and the consequent obesity. These results corroborate those of studies indicating that the C. cardunculus leaf ethanol extract can contribute to the treatment of obesity.

Brazil nut prevents oxidative DNA damage in type 2 diabetes patients.

The Brazil nut (Bertholletia excelsa, H.B.K.) originating from the Amazon region is one of the richest known sources of selenium (Se), a micronutrient that is essential and required for optimal physiological functioning. This mineral presents several health benefits, including improvement of the redox cellular status and maintenance of genomic stability. Knowing that type 2 diabetes mellitus (T2D) is strongly linked to oxidative stress and consequently DNA damage, the aim of this study was to assess the ex vivo antioxidative effects of Se through Brazil nut consumption and its potential in preventing oxidative DNA damage induced by H2O2. In order to accomplish this, the Comet assay (single-cell gel electrophoresis) was used to measure DNA damage in peripheral blood cells harvested before and after supplementation with Brazil nut. Comet assay was also applied ex vivo to measure the potential of Se to prevent oxidative damage to DNA induced by H2O2 in blood of type 2 diabetes patients collected before and after six months of supplementation with Brazil nut. We found that supplementation with Brazil nuts significantly increased serum Se levels. Furthermore, we observed a significant increase in fasting blood glucose after six months of consuming Brazil nuts; however, no significant effect was observed on the levels of glycated hemoglobin. Finally, we noticed that the cells were more resistant to H2O2-induced DNA damage after six months of supplementation with Brazil nut. Thus, consumption of Brazil nuts could decrease oxidative DNA damage in T2D patients, probably through the antioxidative effects of Se.

Anti-genotoxic and anti-mutagenic effects of melatonin supplementation in a mouse model of melanoma.

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (n = 6), melanoma + vehicle (n = 10), PBS + melatonin (n = 6), and melanoma + melatonin (n = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells.

Can fructose influence the development of obesity mediated through hypothalamic alterations?

Epidemiological data from the last decades point to an exponential growth in the number of obese people. Different behavioral factors, mainly associated with food consumption, appear to contribute significantly to its development. Concomitant with increased obesity rates, an increase in the consumption of fructose has been observed; therefore, fructose consumption has been implicated as an important obesogenic factor. However, changes in brain activity due to fructose consumption are possible, especially in relation to hypothalamic satiety mechanisms. In addition, the obese state may provide an environment of chronic inflammation and further contribute to the discontinuation of satiety mechanisms in the hypothalamus. We briefly review the intrinsic alterations to the increased adipose tissue, its connections with the hypothalamus in the control of energy signaling mechanisms and, consequently, the participation of fructose as a co-adjuvant or trigger. Presenting the current context with clinical trials involving human and animal studies, we seek to contribute to a better understanding of the role of fructose in the progression of obesity.

Evaluation of genotoxicity and coumarin production in conventional and organic cultivation systems of Mikania glomerata Spreng.

Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.

Vitamin D3 as adjuvant in the treatment of type 2 diabetes mellitus: modulation of genomic and biochemical instability.

Type 2 diabetes mellitus has undergone a worldwide growth in incidence in the world and has now acquired epidemic status. There is a strong link between type 2 diabetes and vitamin D deficiency. Because vitamin D has beneficial effects on glucose homeostasis, the aim of this study was to evaluate the influence of vitamin D3 supplementation on the modulation of glycaemic control and other metabolic effects, as well as modulation of genomic instability in patients with type 2 diabetes. We evaluated 75 patients with type 2 diabetes, registered in the Integrated Clinics of the University of Southern Santa Catarina. Participants received 4000 IU of vitamin D3 (25(OH)D) supplementation daily for 8 weeks. Blood samples were collected at the beginning and at the end of the supplementation, and 4 weeks after the end of supplementation. The glycidic and lipid profiles [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein and triglycerides], oxidative stress, DNA damage and 25(OH)D levels were evaluated. Vitamin D3 supplementation for 8 weeks showed enough to significantly increase blood levels of 25(OH)D. A significant difference in lipid profile was observed only in non-HDL cholesterol. Significant changes were observed in glucose homeostasis (fasting glucose and serum insulin) and, in addition, a reduction in the parameters of oxidative stress and DNA damage. There was a significant reduction in the values of 25(OH)D 4 weeks after the end of the supplementation, but levels still remained above baseline. Use of vitamin D supplementation can be an ally in the health modulation of patients with type 2 diabetes mellitus.

Evaluation of the effects of fructose on oxidative stress and inflammatory parameters in rat brain.

Hereditary fructose intolerance is an autosomal recessive disorder characterized by the accumulation of fructose in tissues and biological fluids of patients. The disease results from a deficiency of aldolase B, responsible for metabolizing fructose in the liver, kidney, and small intestine. We investigated the effect of acute fructose administration on oxidative stress and neuroinflammatory parameters in the cerebral cortex of 30-day-old Wistar rats. Animals received subcutaneous injection of sodium chloride (0.9 %) (control group) or fructose solution (5 µmol/g) (fructose group). One hour later, the animals were euthanized and the cerebral cortex was isolated. Oxidative stress (levels of thiobarbituric acid-reactive substances (TBA-RS), carbonyl content, nitrate and nitrite levels, 2',7'-dihydrodichlorofluorescein (DCFH) oxidation, glutathione (GSH) levels, as well as the activities of catalase (CAT) and superoxide dismutase (SOD)) and neuroinflammatory parameters (TNF-α, IL-1ß, and IL-6 levels and myeloperoxidase (MPO) activity) were investigated. Acute fructose administration increased levels of TBA-RS and carbonyl content, indicating lipid peroxidation and protein damage. Furthermore, SOD activity increased, whereas CAT activity was decreased. The levels of GSH, nitrate, and nitrite and DCFH oxidation were not altered by acute fructose administration. Finally, cytokines IL-1ß, IL-6, and TNF-α levels, as well as MPO activity, were not altered. Our present data indicate that fructose provokes oxidative stress in the cerebral cortex, which induces oxidation of lipids and proteins and changes of CAT and SOD activities. It seems therefore reasonable to propose that antioxidants may serve as an adjuvant therapy to diets or to other pharmacological agents used for these patients, to avoid oxidative damage to the brain.