RESUMO
The flavanones hesperidin, eriocitrin and eriodictyol were investigated for their prevention of the oxidative stress and systemic inflammation caused by high-fat diet in C57BL/6J mice. The mice received a standard diet (9.5% kcal from fat), high-fat diet (45% kcal from fat) or high-fat diet supplemented with hesperidin, eriocitrin or eriodictyol for a period of four weeks. Hesperidin, eriocitrin and eriodictyol increased the serum total antioxidant capacity, and restrained the elevation of interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and C-reactive protein (hs-CRP). In addition, the liver TBARS levels and spleen mass (g per kg body weight) were lower for the flavanone-treated mice than in the unsupplemented mice. Eriocitrin and eriodictyol reduced TBARS levels in the blood serum, and hesperidin and eriodictyol also reduced fat accumulation and liver damage. The results showed that hesperidin, eriocitrin and eriodictyol had protective effects against inflammation and oxidative stress caused by high-fat diet in mice, and may therefore prevent metabolic alterations associated with the development of cardiovascular diseases in other animals.
Assuntos
Citrus/química , Flavanonas/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Quimiocina CCL2/sangue , Fatores Quimiotáticos/sangue , Colesterol/sangue , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Hesperidina/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/análise , Substâncias Protetoras/farmacologia , Baço/efeitos dos fármacos , Baço/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/sangueAssuntos
Humanos , Aterosclerose/tratamento farmacológico , Aterosclerose/fisiopatologia , Aterosclerose/terapia , Lipoproteínas HDL , Óxido Nítrico , Fumar/efeitos adversos , Trombofilia/complicações , Ácido Ascórbico/uso terapêutico , Aspirina/uso terapêutico , Fatores Quimiotáticos/sangue , Chlamydophila pneumoniae/patogenicidade , Heparina de Baixo Peso Molecular/uso terapêutico , Macrófagos/química , Metaloendopeptidases/uso terapêutico , Proteína C-Reativa , Selectinas/uso terapêutico , TiclopidinaAssuntos
Humanos , Aterosclerose/fisiopatologia , Aterosclerose/tratamento farmacológico , Aterosclerose/terapia , Trombofilia/complicações , Tabagismo/efeitos adversos , Óxido Nítrico , Lipoproteínas HDL , Aspirina/uso terapêutico , Ácido Ascórbico/uso terapêutico , Metaloendopeptidases/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Ticlopidina , Fatores Quimiotáticos/sangue , Macrófagos/química , Proteína C-Reativa/diagnóstico , Chlamydophila pneumoniae/patogenicidade , Selectinas/uso terapêuticoRESUMO
The influence of aging on neutrophil chemotaxis, chemokinesis, and superoxide production was investigated in rats. Animals of two age groups, 3 to 4 months and 20 to 21 months, were used. Equivalent neutrophil chemotactic responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and bacterial lipopolysaccharide (LPS)-activated plasma were observed in both groups of animals, with cells suspended in Hanks' balanced salt solution (HBSS). However, cross-incubation studies in which cells from young adult rats were exposed to plasma from aged donors, then resuspended in HBSS for testing, showed marked changes in the ability of the cells to respond to the chemoattractants. The response to LPS-activated plasma was reduced, whereas responses to fMLP and LTB4 remained unaltered. Previous incubation of the cells with homologous plasma from young donors produced no effect. The inhibitory activity developing with advancing age affected not only chemotaxis but also random movement stimulated by LPS-activated plasma. The inhibitory activity of chemotaxis and chemokinesis in plasma of aged animals was heat labile (56 degrees C), vanished in the presence of a proteolytic enzyme like trypsin, and was maintained after dialysis with 12,000-Mr retention dialysis tubing. The material did not influence superoxide production by stimulated neutrophils. It is suggested that inhibition of neutrophil locomotion with advancing age is associated with a plasma protein capable of interacting with neutrophil receptors for complement-derived chemoattractants. The inhibitory substance might influence neutrophil responses to infection and inflammation in the elderly.
Assuntos
Envelhecimento/fisiologia , Proteínas Sanguíneas/fisiologia , Fatores Quimiotáticos/fisiologia , Quimiotaxia de Leucócito/fisiologia , Proteínas do Sistema Complemento/fisiologia , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Fatores Quimiotáticos/sangue , Quimiotaxia de Leucócito/efeitos dos fármacos , Relação Dose-Resposta a Droga , Leucotrieno B4/farmacologia , Lipopolissacarídeos/fisiologia , Masculino , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/citologia , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Ratos , Ratos Endogâmicos , Superóxidos/metabolismo , Temperatura , Fatores de TempoRESUMO
We have found subnormal amounts of chemotactic activity in zymosan-treated sera from 13 of 29 patients with systemic lupus erythematosus (SLE). As an explanation for this abnormality, the presence of a uniquely specific, heat-stable inhibitor of complement (C5)-derived chemotactic activity has been documented in sera from 11 of these patients. Sera from 2 other patients contained elevated levels of nonspecific, heat-labile chemotactic factor inactivator (CFI) activity. The serum from 1 patient contained the heat-stable inhibitor as well as elevated levels of CFI. Patients with SLE whose sera contained the heat-stable inhibitor had more active disease clinically, but otherwise they were indistinguishable from patients without the inhibitor. When patients with the heat-stable inhibitor improved clinically, this usually was accompanied by a decrease in serum inhibitory activity. Only one episode of bacterial infection was observed among 16 patients with SLE whose sera yielded normal amounts of chemotactic activity after treatment with zymosan. In contrast, 7 of 11 patients with SLE whose sera contained the heat-stable inhibitor suffered serious bacterial infections. The presence of this heat-stable inhibitor in sera from some patients with SLE may contribute, in part, to their increased susceptibility to infection.