ESAV - DZERV - Artigo em revista científica, não indexada ao WoS/Scopus
Permanent URI for this collection
Browse
Browsing ESAV - DZERV - Artigo em revista científica, não indexada ao WoS/Scopus by Author "Alves, R."
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- 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.
- Serum and renal tissue markers of nephropathy in rats under immunosuppressive therapy: cyclosporine vs sirolimusPublication . Sereno, J.; Parada, B.; Rodrigues-Santos, P.; Lopes, P.; Carvalho, E.; Vala, Helena; Teixeira-Lemos, E.; Alves, R.; Figueiredo, A.; Mota, A.; Teixeira, F.; Reis, F.Cyclosporin (CsA) has been progressively replaced by other drugs with putatively fever side effects, including nephrotoxicity and hypertension. Sirolimus (SRL) is one of the main options for management of kidney transplant patients in the post-CsA era. It shows identical efficacy with apparently less cardiorenal side effects than CsA. However, doubts remain concerning the mechanisms of putative renoprotection by SRL as well as the best serum and/or tissue markers for nephropathy, as assessed in this study employing CsA- and SRL-treated rats. Three groups (n = 6) were treated orally during a 6-week protocol: control (vehicle); CsA (5 mg/kg body weight per day Sandimmun Neoral); SRL (1 mg/kg body weight per day Rapamune). Blood pressure and heart rate were assessed with a "tail cuff". Renal dysfunction and morphology were characterized using serum creatinine and blood urea nitrogen (BUN) levels as well as hematoxylin and eosin and periodic acid Schiff staining, respectively. We examined serum concentrations of interleukin (IL)-2, IL-1β, high-sensitivity C-reactive protein, tumor necrosis factor TNF-α, and vascular endothelial growth factor and kidney mRNA expression of interleukin-1β (IL-1β), tumor protein 53 (TP53), mammalian target of rapamycin (mTOR) and proliferating cell nuclear antigen (PCNA), as well as markers of lipid peroxidation in the kidney and serum. Both CsA and SRL induced significant increases in systolic and diastolic blood pressure, but only CsA caused tachycardia. CsA-treated rats also displayed increased serum creatinine and BUN levels, accompanied by mild renal lesions, which were almost absent among SRL-treated rats, which presented hyperlipidemic and hyperglycemic profiles. CsA-induced nephrotoxicity was accompanied by kidney overexpression of inflammatory and proliferative mRNA markers (IL-1β, mTOR and PCNA), which were absent among SRL group. In conclusion, the antiproliferative and antifibrotic character of SRL may explain its less nephrotoxic profile. Renal over expression of mTOR in the CsA-treated group, associated with renal dysfunction and structural damage, reinforces the potential beneft of SRL as a strategy to reduce CsA-evoked nephrotoxicity.