RESUMO
We evaluated how low-level (3 ppm) subchronic inorganic arsenic (iAs) exposure from prenatal developmental stages until adult life affects glucose homeostasis. Biochemical parameters of glucose and lipid metabolism, pancreatic insulin and glycosylated haemoglobin were determined in 4-month-old female offspring of adult Wistar rats. Pancreatic histology was also performed. Statistical comparisons between control and iAs-treated groups were performed by unpaired two-tailed Student's t-test. Statistical significance was set at p<0.05. We found that iAs treatment resulted in an impaired glucose tolerance test, suggestive of impaired glucose metabolism. This group was found to have hyperglycaemia and high levels of HOMA-IR, glycosylated haemoglobin, cholesterol and pancreatic insulin compared to control rats. However, plasma insulin, triglycerides and high-density lipoprotein cholesterol were not different from control rats. Moreover, ß-cell damage found in iAs-treated rats consisted of cells with a nucleus with dense chromatin and predominance of eosinophilic cytoplasm, as well as changes in the pancreatic vasculature. The current study provided evidence that subchronic iAs exposure at 3 ppm from prenatal developmental stages to adult life resulted in damage to pancreatic ß cells, affected insulin secretion and demonstrated altered glucose homeostasis, thus supporting a causal association between iAs exposure and diabetes.
Assuntos
Arsenitos/toxicidade , Transtornos do Metabolismo de Glucose/induzido quimicamente , Células Secretoras de Insulina/efeitos dos fármacos , Exposição Materna , Animais , Intoxicação por Arsênico/fisiopatologia , Arsenitos/administração & dosagem , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Diabetes Mellitus/etiologia , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/patologia , Transtornos do Metabolismo de Glucose/fisiopatologia , Hemoglobinas Glicadas/análise , Hipercolesterolemia/etiologia , Hiperglicemia/etiologia , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Lactação , Pâncreas/irrigação sanguínea , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Gravidez , Ratos , Ratos Wistar , Compostos de Sódio/administração & dosagem , DesmameRESUMO
BACKGROUND: Oxidative stress (OxS) induced by diabetes plays an important role in the development of diabetic nephropathy. Studies have shown that antioxidants are beneficial in its reduction. Vitamin E has been documented as providing the most improvement in the antioxidative status. Recently, pentoxifylline (PTX) has been proposed to have antioxidant properties. AIM: The aim of the study was to assess the ability of two antioxidants to reduce lipid peroxidation and renal hypertrophy in vivo. METHODS: Diabetes was induced by streptozotocin (STZ) in rats. Treatment groups were divided as follows: healthy (H), diabetic without treatment (STZ), PTX treated group (STZ+PTX), and vitamin E supplemented (STZ+E) group. At 8 weeks, kidneys were removed; one was homogenized to quantify lipoperoxide levels (LPOS), and the other was used to study the morphological changes by electron microscopy (EM). Additionally, plasma total antioxidant activity (TAA) was quantified. RESULTS: A reduction in LPOS was observed in both groups: PTX and vitamin E with regard to STZ group. PTX increased TAA compared to STZ+E, which restored it to its normal values. However, both treatments reduced the LPO/TAA ratio to lower basal levels; hence, similar results were obtained in terms of correcting functional parameters. Structural changes in STZ rats included a glomerular membrane thickening, podocyte flattening, as well as loss of fenestration in the endothelial layer. All these changes were less aggressive for treated rats. CONCLUSIONS: Vitamin E and PTX have potential therapeutic properties that may help to retard the rate of deterioration of diabetic kidneys.
Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Rim/efeitos dos fármacos , Pentoxifilina/farmacologia , Vitamina E/farmacologia , Animais , Antioxidantes/uso terapêutico , Nefropatias Diabéticas/etiologia , Hipertrofia , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Pentoxifilina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Estreptozocina , Vitamina E/uso terapêuticoRESUMO
Oxidative damage has been suggested to be a contributing factor in the development to diabetic nephropathy (DN). Recently, there has been evidence that pentoxifylline (PTX) has free radical-scavenging properties; thus, its anti-inflammatory and renoprotective effects may be related to a reduction in reactive oxygen species production. It is likely that the pharmacological effects of PTX include an antioxidant mechanism as shown in in vitro assays. The aim of this study was to evaluate whether the reported renoprotective effects of PTX could be the result of its antioxidant actions in streptozotocin (STZ)-induced DN in rats. The administration of PTX over a period of 8 weeks, in addition to displaying renoprotective effects, caused a significant reduction in lipoperoxide levels (LPOS) in the diabetic kidney (P < 0.05), compared to untreated rats. These levels were comparable to those in the healthy kidney of experimental animals (P > 0.05). All untreated STZ rats exhibited an increase in LPOS as opposed to healthy controls (H) (P < 0.001). The total antioxidant activity (TAA) in plasma was increased significantly already after 2 days of STZ (P < 0.05). When we examined the progression of TAA in STZ rats, there was a significant decrease over 8 weeks (P < 0.05). PTX treatment caused an increase in TAA when compared to untreated STZ rats (P < 0.05). Renal hypertrophy was less evident in PTX-treated STZ than in untreated STZ rats, evaluated by kidney weight/body weight ratio. These results indicate that PTX decreases the oxidative damage induced by these experimental procedures and may increase antioxidant defense mechanisms in STZ-induced diabetes in rats.