Consumo exacerbado de lipídeos provoca dano celular em algumas doenças metabólicas e cardiovasculares / Excessive consumption of fat provokes systemic cellular damage in some metabolic and cardiovascular diseases

OBJECTIVE: To review the deleterious biochemical mechanisms related to changes of oxidative stress and inflammation, provoked by excessive consumption and accumulation of lipids in different tissues, in cardiovascular diseases, diabetes and metabolic syndrome. Data source: This review article was based on papers selected for their relevance from databases such as Science Direct, PubMed and SciELO, published between 1995 and 2014. The search included the following keywords: High-fat diet, obesity, oxidative stress, inflammation. Data synthesis: Evidence suggests that the deleterious effects of lipotoxicity are related to ectopic deposition, activation of lipolysis, formation of lipid metabolites, generation of reactive oxygen species and oxidative stress, as well as to stimulation of inflammatory cascades. In this context, the simultaneous activation of these biochemical mechanisms interferes with intracellular signaling cascades, disrupting homeostasis, leading to systemic cellular damage or even lipoapoptosis. CONCLUSIONS: The identification of the biochemical cellular pathways involved in the process provides an understanding of the molecular mechanisms and, especially, may identify potential therapeutic targets

OBJETIVO: Revisar mecanismos bioquímicos deletérios relacionados com alterações de estresse oxidativo e inflamação ocasionados pelo consumo excessivo e acúmulo de lipídeos em diferentes tecidos, nas doenças cardiovasculares, diabetes e síndrome metabólica. Fonte de dados: Este artigo de revisão baseou-se em artigos científicos, selecionados por sua relevância e provenientes de bases de dados como Science Direct, Scielo e Pubmed, publicados entre 1995 e 2014. A busca contemplou as seguintes palavras-chave: dieta hiperlipídica, obesidade, estresse oxidativo, inflamação. Síntese dos dados: Evidências sugerem que os efeitos deletérios da lipotoxidade estão relacionados com a deposição ectópica, ativação da lipólise, formação de metabólitos lipídicos, geração de espécies reativas e estresse oxidativo, bem como estimulação de cascatas inflamatórias. Nesse contexto, a ativação simultânea desses mecanismos bioquímicos interfere em cascatas de sinalização intracelular, prejudicando a homeostase, levando ao dano celular sistêmico ou até mesmo à lipoapoptose. CONCLUSÕES: A identificação das vias bioquímicas celulares envolvidas proporciona a compreensão dos mecanismos moleculares e, principalmente, pode identificar possíveis alvos terapêuticos

Hepatoprotective and Antioxidant Potential of Organic and Conventional Grape Juices in Rats Fed a High-Fat Diet.

The objective of this study was to investigate the antioxidant and hepatoprotective effect of the chronic use of conventional (CGJ) or organic (OGJ) grape juice from the Bordeaux variety grape on oxidative stress and cytoarchitecture in the liver of rats supplemented with a high-fat diet (HFD) for three months. The results demonstrated that HFD induced an increase in thiobarbituric acid-reactive substances (TBARS), catalase (CAT) activity and 2',7'-dihydrodichlorofluorescein (DCFH) oxidation and a decrease in sulfhydryl content and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. HFD also induced hepatocellular degeneration and steatosis. These alterations were prevented by CGJ and OGJ, where OGJ was more effective. Therefore, it was concluded that HFD induced oxidative stress and liver damage and that the chronic use of grape juice was able to prevent these alterations.

Effect of chronic treatment with conventional and organic purple grape juices (Vitis labrusca) on rats fed with high-fat diet.

Serra Gaucha is described as the most important wine region of Brazil. Regarding cultivars widespread in the Serra Gaucha, about 90 % of the area is occupied by vines of Vitis labrusca that is the most important specie used in grape juice production. The objective of this study was to investigate the antioxidant and neuroprotective effect of chronic intake of purple grape juice (organic and conventional) from Bordo variety (V. labrusca) on oxidative stress in different brain regions of rats supplemented with high-fat diet (HFD) for 3 months. A total of 40 male rats were randomly divided into 4 groups. Group 1 received a standard diet and water, group 2 HFD and water, group 3 HFD and conventional grape juice (CGJ), and group 4 HFD and organic grape juice (OGJ). All groups had free access to food and drink and after 3 months of treatment the rats were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum isolated and homogenized on ice for oxidative stress analysis. We observed that the consumption of calories in HFD and control groups, were higher than the groups supplemented with HFD and grape juices and that HFD diet group gain more weight than the other animals. Our results also demonstrated that HDF enhanced lipid peroxidation (TBARS) and protein damage (carbonyl) in cerebral cortex and hippocampus, reduced the non-enzymatic antioxidants defenses (sulfhydryl) in cerebral cortex and cerebellum, reduced catalase and superoxide dismutase activities in all brain tissues and enhanced nitric oxide production in all cerebral tissues. CGJ and OGJ were able to ameliorate these oxidative alterations, being OGJ more effective in this protection. Therefore, grape juices could be useful in the treatment of some neurodegenerative diseases associated with oxidative damage.

Toxicological evaluation of chronic exposure to the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one in male rats.

The aim of this study was to evaluate the effect of chronic treatment with the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some behavioral and biochemical parameters in the brain, liver, kidney and serum of 90-day-old male Wistar rats. The animals received the organoselenium at doses of 125, 250 or 500 µg/kg body weight intraperitoneally once daily for 30 days. Results showed that chronic treatment with this compound induced behavioral changes in animals, such as increasing of rearing at dose of 250 µg/kg and increasing of ambulation in all concentrations tested. On the other hand, we did not observe any alterations in the body weight gain of the animals. Moreover, the activity of the enzyme creatine kinase (CK) decreased in the cerebral cortex, cerebellum and kidney and increased in the liver after the chronic treatment with the organoselenium compound at dose of 500 µg/kg. The compound also increased aspartate aminotransferase (AST) and urea levels in serum of rats at 500 µg/kg. Glucose, cholesterol, triglycerides, creatinine, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were not changed by the treatment. Our results thus show that chronic administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one is able to significantly change the activity of CK in Wistar rats, resulting in a change in cellular energy homeostasis in these tissues, liver damage and behavioral changes in the animals studied.