RESUMO
The mechanisms underlying diabetic encephalopathy, are only partially understood. In this study, we try to address the mechanisms of diabetes induced damage and whether docosahexaenoic acid (DHA) could attenuate the degenerative changes in diabetic hippocampus in a rodent model of diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin. Animals were divided into the following experimental groups: control rats; control animals treated with DHA; untreated diabetic rats; diabetic rats treated with insulin; diabetic rats treated with DHA; diabetic rats treated with insulin and DHA. At the end of week 12, rats were killed and one of the hemispheres was cryosectioned and the other was dissected and hippocampi homogenized. The number of bromodeoxyuridine positive cells in the hippocampus of diabetic rats was decreased, and the latency time to find the platform in the Morris Water maze was significantly increased in the diabetic rats when compared to controls. No changes where observed in the expression of p21 in the hippocampus of control and diabetic rats. Biochemical markers of oxidative stress were altered in hippocampus of diabetic rats, and NFκB-positive cells were increased in the hippocampus of diabetic rats when compared to controls. Treatment with DHA, or the combination of DHA with insulin, significantly restored to control levels all the values mentioned above. Our findings confirm a pivotal role for oxidative stress as well as NF-κB, but not p21, in diabetes-induced hippocampal impairments. Administration of DHA as well as insulin prevented the changes induced by diabetes in hippocampus.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Hipocampo/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Western Blotting , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Ratos , Ratos WistarRESUMO
We have previously shown that the use of a combination of antioxidants delayed the degeneration process in rd1 mouse retina. In an effort to understand the mechanism of action of these substances (zeaxanthin, lutein, alpha-lipoic acid, glutathione, and Lycium barbarum extract) the changes in the levels of several proteins and oxidative stress markers in the rd1 retina have been studied. The treatment increased glutathione peroxidase activity and glutathione levels and decreased cystine concentrations in rd1 retinas. Considering all the results obtained from treated and untreated animals, a high correlation was present between glutathione concentration and glutathione peroxidase activity, and there was a negative correlation between glutathione retinal concentration and number of TUNEL-positive cells. No difference was observed between the numbers of nNOS- and NADPH-diaphorase-positive cells in treated and untreated rd1 mice. Thiol contents and thiol-dependent peroxide metabolism seem to be directly related to the survival of photoreceptors in rd1 mouse retina.
Assuntos
Antioxidantes/administração & dosagem , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/metabolismo , Glutationa/metabolismo , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/genética , Células Cultivadas , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/genética , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Lycium , Camundongos , Camundongos Endogâmicos C3H , Camundongos Mutantes , Mutação/genética , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo I/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patologia , Degeneração RetinianaRESUMO
PURPOSE: To assess the effect of docosahexanoic acid (DHA) and lutein (both compounds with anti-inflammatory and antioxidant properties) on experimental diabetic retinopathy. METHODS: Male Wistar rats were studied: non-diabetic controls, untreated diabetic controls, and diabetic rats were treated with DHA and lutein or the combination of DHA + insulin and lutein + insulin for 12 weeks. Oxidative stress and inflammatory markers, apoptosis, and functional tests were studied to confirm biochemical and functional changes in the retina of diabetic rats. Malondialdehyde (MDA), glutathione concentrations (GSH), and glutathione peroxidase activity (GPx) were measured as oxidative stress markers. TUNEL assay and caspase-3 immunohistochemistry and electroretinogram were performed. RESULTS: Diabetes increases oxidative stress, nitrotyrosine concentrations, and apoptosis in the retina. At 12 weeks after onset of diabetes, total thickness of retinas of diabetic rats was significantly less than that in control rats. Specifically, the thickness of the outer and inner nuclear layers was reduced significantly in diabetic rats and demonstrated a loss of cells in the GCL. These retinal changes were avoided by the administration of insulin and DHA and lutein alone or in combination with insulin. Impairment of the electroretinogram (b-wave amplitude and latency time) was observed in diabetic rats. DHA and lutein prevented all these changes even under hyperglycemic conditions. CONCLUSIONS: Lutein and DHA are capable of normalizing all the diabetes-induced biochemical, histological, and functional modifications. Specifically, the cell death mechanisms involved deserve further studies to allow the proposal as potential adjuvant therapies to help prevent vision loss in diabetic patients.