Browsing by Author "Rocha-Pereira, P."
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- Aging is associated with impaired renal function, INF-gamma induced inflammation and with alterations in iron regulatory proteins gene expressionPublication . Costa, E.; Fernandes, J.; Ribeiro, S.; Garrido, P.; Rocha-Pereira, P.; Coimbra, S.; Catarino, C.; Reis, F.; Belo, L.; Bronze-da-Rocha, E.; Vala, Helena; Alves, R.; Santos-Silva, A.Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, ironmetabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associatedwith INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression.
- Cyclosporine A-induced nephrotoxicity is ameliorated by dose reduction and conversion to Sirolimus in the ratPublication . Sereno, J.; Vala, Helena; Nunes, S.; Rocha-Pereira, P.; Carvalho, E.; Alves, R.; Teixeira, F.; Reis, F.Side-effect minimization strategies to avoid serious side-effects of cyclosporine A (CsA), such as nephrotoxicity, have been mainly based on dose reduction and conversion to other putatively less nephrotoxic drugs, such as sirolimus (SRL), an inhibitor of the mammalian target of rapamycin. This study intended to evaluate the impact of protocols based on CsA dose reduction and further conversion to SRL on kidney function and lesions, based on serum, urine and renal tissue markers. The following 3 groups (n=6) were tested during a 9-week protocol: control (vehicle); CsA (5 mg/kg/day) and Red + Conv (CsA 30 mg/kg/day during 3 weeks + 3 weeks with CsA 5 mg/kg/day + SRL 1 mg/kg/day during the last 3 weeks). The following parameters were analysed: blood pressure, heart rate and biochemical data; serum and urine contents and clearances of creatinine, urea and neutrophil gelatinase-associated lipocalin, as well as, glomerular filtration rate; kidney lipid peroxidation and clearance; kidney lesions were evaluated and protein expression was performed by immunohistochemistry. After the first 3 weeks of CsA (30 mg/kg/day) treatment animals showed body weight loss, hypertension, tachycardia, as well as, increased serum levels of non-HDL cholesterol, glucose, triglycerides, creatinine and urea, accompanied by decreased GFR and insulin levels. In addition, a significant increase in the expression of connective tissue growth factor, Kim-1, mammalian target of rapamycin, nuclear factor-κβ1 and transforming growth factor-β was found in the kidney, accompanied by extensive renal damage. The following 3 weeks with CsA dose reduction revealed amelioration of vascular and glomerular lesions, but without significant tubular improvement. The last 3 weeks with the conversion to sirolimus revealed high serum and urine NGAL contents but the CsA-evoked renal damage was substantially ameliorated, by reduced of connective tissue growth factor, mammalian target of rapamycin, nuclear factor-κβ1 protein expression. In conclusion, CsA nephrotoxicity is dose dependent and moderate dysfunction could be ameliorated/prevented by SRL conversion, which could be pivotal for the preservation of kidney function and structure.
- Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty ratsPublication . Teixeira-Lemos, Edite; Reis, F.; Baptista, S.; Pinto, R.; Sepodes, B.; Vala, Helena; Rocha-Pereira, P.; et al.Objective In the present study we evaluated the effect of exercise on the plasma levels of proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and the anti-inflammatory molecule uric acid in the Zucker diabetic fatty (ZDF) rats that are more prone to develop type 2 diabetes mellitus. Methods Sixteen obese ZDF (Gmi fa/fa) rats (8 wk old, 228.40 ± 4.05 g) were randomly assigned to one of two groups (n = 8 each): an exercise-trained group and a sedentary one. In addition, 16 lean ZDF (Gmi +/+) rats (8 wk old, 199.00 ± 3.50 g) were subjected to identical sedentary and exercise conditioning (n = 8 each). Initially, rats swam 15 min/d (5 d/wk) in a 36°C bath. The exercise protocol was gradually increased by 15 min/d until a swimming period of 1 h/d (1 wk) was attained. Thereafter, rats swam 1 h/d, 3 d/wk, for an additional period of 11 wk. Rats were sacrificed 48 h after the last training period and the blood and pancreas were collected. Circulating levels of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, insulin, uric acid, IL-6, and TNF-α were assessed. The concentrations of proinflammatory cytokines in the pancreas were also evaluated. Results In the diabetic ZDF (fa/fa) rats, exercise decreased hyperuricemia (−37.3%) and IL-6 and TNF-α levels (−16.9% and −12.7% respectively) and maintained the weight of the pancreas at near normal. Immunohistochemistry revealed a marked decrease in the expression of TNF-α and IL-6 in the pancreatic islet cells of ZDF (fa/fa) rats. Conclusion These results indicate that aerobic exercise is anti-inflammatory in nature.
- Exercise training is associated with improved levels of C-reactive protein and adiponectin in ZDF (type 2) diabetic rats.Publication . Teixeira de Lemos, Edite; Reis, Flávio; Baptista, Sofi a; Pinto, Rui; Sepodes, Bruno; Vala, Helena; Rocha-Pereira, P.; Silva, Alice Santos; Teixeira, FredericoChronic low-grade systemic infl ammation is a feature of such chronic diseases as cardiovascular disease and type 2 diabetes (T2D). There is evidence that regular exercise is effective as a treatment in these situations. This study intended to assess the levels of two infl ammatory mediators, C-reactive protein (CRP) and adiponectin, in Zucker Diabetic Fatty (ZDF, fa/fa) rats, an experimental model of T2D, and to determine whether exercise-induced changes in insulin resistance could be explained by modifi cations in these infl ammation markers. Material/Methods: Male ZDF (Gmi fa/fa) rats and their littermates (Gmi +/+), aged 8 weeks, were randomly assigned in two groups: an exercise trained and a sedentary one. Swimming was conducted 1 h/day 3 days/week for 12 weeks. The rats were sacrifi ced 48 h after the last round of exercise. Rats had their body weight, insulin, adiponectin, CRP, as well as glucose, total cholesterol, triglycerides, MDA, and SOD measured and HOMA-IR calculated before and after the 12-week swimming training. Results: In the ZDF (fa/fa) rats underwent swimming exercise, all the metabolic abnormalities were totally or partially prevented ( p<0.001), namely the hyperglycemic, hyperinsulinemic, and dyslipidemic pattern observed in their sedentary counterparts. Furthermore, even without body weight change, a plasma adiponectin increase (28.0%) and a CRP decrease (12.7%) were also observed. Conclusions: A 12-week thrice-weekly swimming training was associated with improved measures of chronic in- fl ammation markers as measured by adiponectin and CRP. Moreover, improvements in insulin sensitivity resulting from swimming exercise appeared to be related to changes in these infl ammatory mediators.