RESUMO
The immune system plays a crucial role in determining the implantation outcome, and macrophages are in the frontline of the inflammatory processes. Further, cellular oxidative stress resulting from the material recognition can influence how cell responses develop. Considering this, the aim of this study was to study oxidative stress and macrophages phenotypes in response to sol-gel materials with distinct in vivo outcomes. Four materials were selected (70M30T and 35M35G30T, with high biocompatibility, and 50M50G and 50V50G, with low biocompatibility). Gene expression, immunocytochemistry and cytokine secretion profiles for M1 and M2 markers were determined. Moreover, oxidative stress markers were studied. Immunocytochemistry and ELISA showed that 50M50G and 50V50G lead to a higher differentiation to M1 phenotype, while 70M30T and 35M35G30T promoted M2 differentiation. In oxidative stress, no differences were found. These results show that the balance between M1 and M2, more than individual quantification of each phenotype, determines a biomaterial outcome.
Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Inflamação/patologia , Animais , Forma Celular/efeitos dos fármacos , Forma Celular/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Macrófagos/ultraestrutura , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Células RAW 264.7 , Coloração e RotulagemRESUMO
Ethanol abuse is a common issue in individuals with sedentary lifestyles, unbalanced diets, and metabolic syndrome. Both ethanol abuse and metabolic syndrome have negative impacts on the central nervous system, with effects including cognitive impairment and brain oxidative status deterioration. The combined effects of ethanol abuse and metabolic syndrome at a central level have not yet been elucidated in detail. Thus, this work aims to determine the effects of ethanol intake on a mouse model of metabolic syndrome at the behavioral and biochemical levels. Seven-week-old male control (B6.V-Lep ob/+JRj) and leptin-deficient (metabolic syndrome) (B6.V-Lep ob/obJRj) mice were used in the study. Animals were divided into four groups: control, ethanol, obese, and obese-ethanol. Ethanol consumption was monitored for 6 weeks. Basal glycemia, insulin, and glucose overload tests were performed. To assess short- and long-term memory, an object recognition test was used. In order to assess oxidative status in mouse brain samples, antioxidant enzyme activity was analyzed with regard to glutathione peroxidase, glutathione reductase, glutathione, glutathione disulfide, lipid peroxidation products, and malondialdehyde. Ethanol intake modulated the insulin response and impaired the oxidative status in the ob mouse brain.
Assuntos
Modelos Animais de Doenças , Etanol/farmacologia , Síndrome Metabólica/metabolismo , Receptores para Leptina/deficiência , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Depressores do Sistema Nervoso Central/administração & dosagem , Depressores do Sistema Nervoso Central/farmacologia , Etanol/administração & dosagem , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Humanos , Insulina/sangue , Insulina/metabolismo , Masculino , Malondialdeído/metabolismo , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/sangue , Obesidade/genética , Obesidade/metabolismo , Receptores para Leptina/genéticaRESUMO
BACKGROUND: Ethanol (EtOH), one of the most widely consumed substances of abuse, can induce brain damage and neurodegeneration. EtOH is centrally metabolized into acetaldehyde, which has been shown to be responsible for some of the neurophysiological and cellular effects of EtOH. Although some of the consequences of chronic EtOH administration on cell oxidative status have been described, the mechanisms by which acute EtOH administration affects the brain's cellular oxidative status and the role of acetaldehyde remain to be elucidated in detail. METHODS: Swiss CD-I mice were pretreated with the acetaldehyde-sequestering agent d-penicillamine (DP; 75 mg/kg, i.p.) or the antioxidant lipoic acid (LA; 50 mg/kg, i.p.) 30 minutes before EtOH (2.5 g/kg, i.p.) administration. Animals were sacrificed 30 minutes after EtOH injection. Glutathione peroxidase (GPx) mRNA levels; GPx and glutathione reductase (GR) enzymatic activities; reduced glutathione (GSH), glutathione disulfide (GSSG), glutamate, g-L-glutamyl-L-cysteine (Glut-Cys), and malondialdehyde (MDA) concentrations; and protein carbonyl group (CG) content were determined in whole-brain samples. RESULTS: Acute EtOH administration enhanced GPx activity and the GSH/GSSG ratio, while it decreased GR activity and GSSG concentration. Pretreatment with DP or LA only prevented GPx activity changes induced by EtOH. CONCLUSIONS: Altogether, these results show the capacity of a single dose of EtOH to unbalance cellular oxidative homeostasis.