Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats.

Diabetes mellitus (DM) causes important modifications in the availability and use of different energy substrates in various organs and tissues. Similarly, dietary manipulations such as high fat diets also affect systemic energy metabolism. However, how the brain adapts to these situations remains unclear. To investigate these issues, control and alloxan-induced type I diabetic rats were fed either a standard or a high fat diet enriched with advanced glycation end products (AGEs) (HAGE diet). The HAGE diet increased their levels of blood ketone bodies, and this effect was exacerbated by DM induction. To determine the effects of diet and/or DM induction on key cerebral bioenergetic parameters, both ketone bodies (β-hydroxybutyric acid) and lactate oxidation were measured. In parallel, the expression of Monocarboxylate Transporter 1 (MCT1) and 2 (MCT2) isoforms in hippocampal and cortical slices from rats submitted to these diets was assessed. Ketone body oxidation increased while lactate oxidation decreased in hippocampal and cortical slices in both control and diabetic rats fed a HAGE diet. In parallel, the expression of both MCT1 and MCT2 increased only in the cerebral cortex in diabetic rats fed a HAGE diet. These results suggest a shift in the preferential cerebral energy substrate utilization in favor of ketone bodies in animals fed a HAGE diet, an effect that, in DM animals, is accompanied by the enhanced expression of the related transporters

Relação entre diminuição no desempenho comportamental e aumento em lipoperoxidação no sistema nervoso de ratos wistar tratados cronicamente com vitamina A e submetidos a hemi-parkinsonismo

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Development and characterization of blends formulated with banana peel and banana pulp for the production of blends powders rich in antioxidant properties

Abstract The food product industry is increasingly looking for foods with nutritional properties that can provide health benefits. Additionally, a challenge for the food industry is the use of all raw materials. For these reasons, banana peel that is a raw material from Banana (Musa spp.) fruit emerges as potential for new food product development. Here, we developed powder blends using a lyophilization process for the preparation of flour to potential use in cookies, bread, and pasta products. Three formulations were designed; the main difference in the formulations was the use of banana peel concentration. Our results showed that blends produced with banana peel presented physical–chemical properties considered suitable for use in food industry. Moreover, the evaluated morphological parameters reveal the properties of the powders. The blends formulated with banana peel have more antioxidant properties, showing that the banana peel may be an attractive option to generate powders with high antioxidant properties

Reverse engineering the neuroblastoma regulatory network uncovers MAX as one of the master regulators of tumor progression

Neuroblastoma is the most common extracranial tumor and a major cause of infant cancer mortality worldwide. Despite its importance, little is known about its molecular mechanisms. A striking feature of this tumor is its clinical heterogeneity. Possible outcomes range from aggressive invasion to other tissues, causing patient death, to spontaneous disease regression or differentiation into benign ganglioneuromas. Several efforts have been made in order to find tumor progression markers. In this work, we have reconstructed the neuroblastoma regulatory network using an information-theoretic approach in order to find genes involved in tumor progression and that could be used as outcome predictors or as therapeutic targets. We have queried the reconstructed neuroblastoma regulatory network using an aggressive neuroblastoma metastasis gene signature in order to find its master regulators (MRs). MRs expression profiles were then investigated in other neuroblastoma datasets so as to detect possible clinical significance. Our analysis pointed MAX as one of the MRs of neuroblastoma progression. We have found that higher MAX expression correlated with favorable patient outcomes. We have also found that MAX expression and protein levels were increased during neuroblastoma SH-SY5Y cells differentiation. We propose that MAX is involved in neuroblastoma progression, possibly increasing cell differentiation by means of regulating the availability of MYC:MAX heterodimers. This mechanism is consistent with the results found in our SH-SY5Y differentiation protocol, suggesting that MAX has a more central role in these cells differentiation than previously reported. Overexpression of MAX has been identified as anti-tumorigenic in other works, but, to our knowledge, this is the first time that the link between the expression of this gene and malignancy was verified under physiological conditions

Influences of the polymorphisms of the Sod2 gene (rs4880) on the motility and vigor of X- and Y-bearing sperm at different pH values

Superoxide dismutase 2 (SOD2) is an antioxidant enzyme that appears phylogenetically conserved. However, functional Sod2 polymorphisms have been studied, and the specific polymorphisms are related to activity alterations of the SOD2 enzyme. An example of a polymorphism of SOD2 is Val16Ala (rs4880), which has been identified in exon 2 of the human Sod2 gene. This polymorphism is recognized as a single nucleotide polymorphism (SNP) and alters the conformation of SOD2. Additionally, recent studies have shown that the Ala16 Val polymorphism in Sod2 can be related to different pathological diseases. In these terms, the objective of the present study was to evaluate whether the polymorphism of SOD2 in Val16Ala (rs4880) influences the motility and vigor of X- and Y-bearing sperm at different pH values promoting sperm selection. We found that polymorphism rs4880 at normal pH conditions can result in alterations in the activity of superoxide dismutase in the sperm through different assay analyses. Moreover, compelling modulation evidence indicates that this effect could also mediate seminal plasma redox alterations and consequently can play an important role in sperm physiology, fertilization, and postfertilization

Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation

The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with infammation in most cell types. RAGE up-regulates the expression of proinfammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson’s disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 μg per rat), injected concomitantly with 6-OHDA (10 μg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fbrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was signifcantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory defcits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinfammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may ofer perspectives for therapeutic approaches

Cerebral ketone body oxidation is facilitated by a high fat diet enriched with advanced glycation end products in normal and diabetic rats

Diabetesmellitus(DM)causesimportantmodificationsintheavailabilityanduseofdifferentenergysubstratesinvariousorgansandtissues.Similarly,dietarymanipulationssuchashighfatdietsalsoaffectsystemicenergymetabolism.However,howthebrainadaptstothesesituationsremainsunclear.Toinvestigatetheseissues,controlandalloxan-inducedtypeIdiabeticratswerefedeitherastandardorahighfatdietenrichedwithadvancedglycationendproducts(AGEs)(HAGEdiet).TheHAGEdietincreasedtheirlevelsofbloodketonebodies,andthiseffectwasexacerbatedbyDMinduction.Todeterminetheeffectsofdietand/orDMinductiononkeycerebralbioenergeticparameters,bothketonebodies(b-hydroxybutyricacid)andlactateoxidationweremeasured.Inparallel,theexpressionofMonocarboxylateTransporter1(MCT1)and2(MCT2)isoformsinhippocampalandcorticalslicesfromratssubmittedtothesedietswasassessed.KetonebodyoxidationincreasedwhilelactateoxidationdecreasedinhippocampalandcorticalslicesinbothcontrolanddiabeticratsfedaHAGEdiet.Inparallel,theexpressionofbothMCT1andMCT2increasedonlyinthecerebralcortexindiabeticratsfedaHAGEdiet.TheseresultssuggestashiftinthepreferentialcerebralenergysubstrateutilizationinfavorofketonebodiesinanimalsfedaHAGEdiet,aneffectthat,inDManimals,isaccompaniedbytheenhancedexpressionoftherelatedtransporters

Turnera subulata Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

In South America, particularly in the Northeastern regions of Brazil, Turnera subulata leaf extract is used as an alternative traditional medicine approach for several types of chronic diseases, such as diabetes, hypertension, chronic pain, and general inflammation. Despite its widespread use, little is known about the medicinal properties of the plants of this genus. In this study, we evaluate the antioxidant and anti-inflammatory of T. subulata leaf extract in an in vitro model of inflammation, using lipopolysaccharide-stimulated RAW-264.7 macrophage cell line. We observed that cotreatment with T. subulata leaf extract was able to reduce the oxidative stress in cells due to inflammatory response. More importantly, we observed that the leaf extract was able to directly modulate inflammatory response by altering activity of members of the mitogen-activated protein kinase pathways. Our results demonstrate for the first time that T. subulata have antioxidant and anti-inflammatory properties, which warrant further investigation of the medicinal potential of this species.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140112/1/jmf.2016.0047.pd

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development

Background: Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow. Methods: Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated. Results: An increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow. Conclusions: ECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult