THE EFFECT OF INTERMITTENT HYPOXIC TRAINING UNDER OXIDATIVE STRESS PARAMETERS IN WISTAR RATS FED ON STANDARD AND HIGH FAT DIET

Considerando-se que dietas ricas em gordura levam ao estresse oxidativo, causando lesões nas células e que o treinamento hipóxico intermitente (THI) aumenta as defesas antioxidantes endógenas em diversas situações, o objetivo deste estudo foi avaliar o efeito do THI em parâmetros de estresse oxidativo e defesas antioxidantes em fígado de ratos Wistar alimentados com dieta rica em gordura e/ou dieta padrão. Ratos Wistar foram divididos em grupos alimentados com dieta padrão ou rica em gordura. Os grupos foram submetidos a hipóxia intermitente (HI), 15 minutos HI (14-11% O2) intercalados com cinco minutos de re-oxigenação ou sessões de normóxia (N) (21% O2), por um período de duas horas diárias durante 30 dias. Os ratos Wistar alimentados com dieta padrão, e submetidas a HI, apresentaram uma redução de 37,7% na concentração de substâncias reativas ao ácido tiobarbitúrico (TBARS) e aumento de 34,66% e 39,8% no conteúdo de superóxido dismutase (SOD) e catalase (CAT), respectivamente, em comparação com o seu controlo (normoxia). No grupo com dieta rica em gordura, não houve diferença estatística entre os subgrupos HI e N. Nossos dados, que demonstram que o THI possui efeito antioxidante no fígado de ratos Wistar, argumentam em favor do uso alternativo de protocolos de hipoxia intermitente no tratamento de determinadas patologias

Long-Term Aspartame Administration Leads to Fibrosis, Inflammasome Activation, and Gluconeogenesis Impairment in the Liver of Mice

Background: Aspartame is an artificial sweetener used in foods and beverages worldwide. However, it is linked to oxidative stress, inflammation, and liver damage through mechanisms that are not fully elucidated yet. This work aimed to investigate the effects of long-term administration of aspartame on the oxidative and inflammatory mechanisms associated with liver fibrosis progression in mice. Methods: Mice were divided into two groups with six animals each: control and aspartame. Aspartame (80 mg/kg, via oral) or vehicle was administrated for 12 weeks. Results: Aspartame caused liver damage and elevated serum transaminase levels. Aspartame also generated liver fibrosis, as evidenced by histology analysis, and pro-fibrotic markers’ upregulation, including transforming growth factor β 1, collagen type I alpha 1, and alpha-smooth muscle actin. Furthermore, aspartame reduced nuclear factor erythroid 2-related factor 2 (Nrf2) activation and enzymatic antioxidant activity and increased lipid peroxidation, which triggered NOD-like receptor containing protein 3 (NLRP3) inflammasome activation and p53 induction. Furthermore, aspartame reduced peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) levels, possibly through p53 activation. This PGC-1α deficiency could be responsible for the changes in lipid profile in serum, total lipid accumulation, and gluconeogenesis impairment in liver, evidenced by the gluconeogenic enzymes’ downregulation, thus causing hypoglycemia. Conclusions: This work provides new insights to understand the mechanisms related to the adverse effects of aspartame on liver tissue

The Protective Effect of N-Acetylcysteine on Oxidative Stress in the Brain Caused by the Long-Term Intake of Aspartame by Rats

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg(-1), i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg(-1)). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.Fil: Finamor, Isabela A.. Universidade Federal de Santa Maria; BrasilFil: Ourique, Giovana M.. Universidade Federal de Santa Maria; BrasilFil: Pês, Tanise S.. Universidade Federal de Santa Maria; BrasilFil: Saccol, Etiane M. H.. Universidade Federal de Santa Maria; BrasilFil: Bressan, Caroline A.. Universidade Federal de Santa Maria; BrasilFil: Scheid, Taína. Universidade Federal do Rio Grande do Sul; BrasilFil: Baldisserotto, Bernardo. Universidade Federal de Santa Maria; BrasilFil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Partata, Wânia A.. Universidade Federal do Rio Grande do Sul; BrasilFil: Pavanato, Maria A.. Universidade Federal do Rio Grande do Sul; Brasi

Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice

No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ​​(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ​​(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway. Keywords: Aspartame, Cysteine, S-adenosylmethionine, N-acetylcystein

Effects of parboiled rice diet on oxidative stress parameters in kidney of rats with streptozotocin-induced diabetes

The effect of parboiled rice (PR) and white rice (WR) diets on oxidative stress (OS) parameters was investigated in the kidneys of rats with streptozotocin-induced diabetes (40mg kg-1, iv). The experimental groups (n=8) were control fed with PR (CPR), control fed with WR, diabetic fed with PR, and diabetic fed with WR. After 30 days of treatment, all animals were anesthetized and exsanguinated before removal of kidneys, which were used to determine thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, carbonyl protein, superoxide dismutase, catalase, glutathione peroxidase (GPx), glutathione reductase, glutathione-S-transferase activities, and levels of glutathione (GSH). Total phenolic compounds were determined in WR and PR grains. Our data indicated that diabetes induced increase in TBARS and lipid hydroperoxides levels. Although PR has not prevented the rise in the levels of these measurements, its consumption by our animals resulted in higher GPx activity and GSH content than that of the CPR. Moreover, PR also presented concentration of total phenolic compounds 127% higher than WR grains. Thus, its consumption in this diabetic condition is suggested because this seems to confer greater protection against OS in the renal tissue of diabetic animals. © Copyright 2012, Mary Ann Liebert, Inc.Fil: Finamor, Isabela A.. Federal University of Santa Maria; BrasilFil: Saccol, Etiane M. H.. Federal University of Santa Maria; BrasilFil: Gabriel, Diogo. Federal University of Santa Maria; BrasilFil: Ourique, Giovana M.. Federal University of Santa Maria; BrasilFil: Riffel, Ana P.K.. Federal University of Santa Maria; BrasilFil: Konrad, Signorá P.. University of Vale do Rio dos Sinos; BrasilFil: Belló Klein, Adriane. Universidade Federal do Rio Grande do Sul; BrasilFil: Partata, Wania. Universidade Federal do Rio Grande do Sul; BrasilFil: Baldisserotto, Bernardo. Federal University of Santa Maria; BrasilFil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Pavanato, Maria A.. Federal University of Santa Maria; Brasi

Humic acid and moderate hypoxia alter oxidative and physiological parameters in different tissues of silver catfish (Rhamdia quelen)

Aquatic animals are naturally exposed simultaneously to environments with different concentrations of humic acid (HA) and seasonal or daily variations of dissolved oxygen (DO) levels. This study investigated the effects of simultaneous exposure to different HA and DO levels on plasma ion levels and some hematological and oxidative parameters in different tissues of silver catfish (Rhamdia quelen). The fish were exposed to 0, 2.5 or 5 mg L(-1) HA for 120 h. After this period, each group was divided into two groups: normoxia and hypoxia. Exposure to the different DO levels lasted 96 h, totaling 216 h of experimentation. At the end of the experimental period, blood sampling was performed, and the fish were euthanized prior to the excision of the gills and the brain to evaluate hematological and oxidative parameters. To verify the antioxidant capacity of HA, total phenolic compounds were measured. In general, all tissues of silver catfish exposed simultaneously to hypoxia and different HA concentrations showed a reduction in lipid peroxidation levels, as well as a modulation of the antioxidant system. These effects occurred in an HA concentration-dependent manner. Thus, HA is beneficial to silver catfish exposed to hypoxia. These beneficial effects can be attributed, most likely, to the action of the different HA constituents and functional groups, including phenolic compounds, which have antioxidant properties.Fil: Riffel, Ana P. K.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Saccol, Etiane M. H.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Finamor, Isabela A.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Ourique, Giovana M.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Gressler, Luciane T.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Parodi, Thaylise V.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Goulart, Luis O. R.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Llesuy, Susana Francisca. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Baldisserotto, Bernardo. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; BrasilFil: Pavanato, María A.. Universidade Federal de Santa Maria. Departamento de Fisiologia e Farmacologia; Brasi

Effect of diets enriched with rutin on blood parameters, oxidative biomarkers and pituitary hormone expression in silver catfish (Rhamdia quelen)

The effects of adding rutin to the diet (0, 0.15 or 0.30 %) of silver catfish for 21 days on blood parameters, oxidative stress biomarkers and pituitary hormones expression were investigated. Fish that received the diet containing 0.15 % rutin exhibited reduced plasma cortisol levels. The levels of lipid peroxidation were lowered in the all tissues of animals receiving the diet containing rutin. Rutin increased the activity of the superoxide dismutase (SOD), catalase (CAT), nonprotein thiols (NPSH), ascorbic acid content (AA) and total reactive antioxidant potential (TRAP) in the brain; glutathione S-transferase (GST) activity and TRAP in the gills; SOD, CAT and GST activity, NPSH, AA levels and TRAP in the liver; CAT and GST activity and TRAP levels in the kidneys; and glutathione peroxidase activity, NPSH, AA levels and TRAP in the muscle. There were no changes regarding the expression of growth hormone, prolactin and somatolactin in fish fed with the diet containing rutin when compared with the control. The supplementation of rutin to the diet of fish is beneficial because it increases the antioxidant responses of tissues.Fil: Pês, Tanise S.. Universidade Federal de Santa Maria; BrasilFil: Saccol, Etiane M. H.. Universidade Federal de Santa Maria; BrasilFil: Ourique, Giovana M.. Universidade Federal de Santa Maria; BrasilFil: Londero, Érika P.. Universidade Federal de Santa Maria; BrasilFil: Gressler, Luciane T.. Universidade Federal de Santa Maria; BrasilFil: Finamor, Isabela A.. Universidade Federal de Santa Maria; BrasilFil: Rotili, Daniel A.. Universidade Federal de Santa Maria; BrasilFil: Golombieski, Jaqueline I.. Universidade Federal de Santa Maria; BrasilFil: Glanzner, Werner G.. Universidade Federal de Santa Maria; BrasilFil: Llesuy, Susana Francisca. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Gonçalves, Paulo B. D.. Universidade Federal de Santa Maria; BrasilFil: Radünz Neto, João. Universidade Federal de Santa Maria; BrasilFil: Baldisserotto, Bernardo. Universidade Federal de Santa Maria; BrasilFil: Pavanato, Maria A.. Universidade Federal de Santa Maria; Brasi