Browsing by Author "Parada, B."
Now showing 1 - 7 of 7
Results Per Page
Sort Options
- Caracterização hemorreológica, bioquímica e cardiovascular num modelo de doença renal crónica moderada em ratoPublication . Garrido, P.; Costa, E.; Teixeira-Lemos, E.; Parada, B.; Teixeira, M.; Santos, P.; Piloto, N.; Sereno, J.; Alves, R.; Pinto, R.; Rocha-Pereira, P.; Figueiredo, A.; Nunes, S.; Romão, A. M.; Carvalho, L.; Couceiro, P.; Belo, L.; Santos-Silva, A.; Teixeira, F.; Reis, F.Chronic kidney disease (CKD) is a major public health problem throughout the world. The major outcomes include a rapid progression, with development of anaemia and serious complications, namely thromboembol ic and cardiovascular events. The pathophysiological alterations depend on the CKD degree, which will also determine the moment to initiate hemodialysis and recombinant erythropoietin (rhEPO) therapies Thus, the cardio-renal complication might be better prevented or delayed if CKD patients are earlier identified and treated for the associated anaemia, which will depend on a better characterization of moderate stages of CKD. This study aimed to characterization an animal of model of moderate CKD induced by partial (%) nephrectomy, by evaluating hemorheological, biochemical and cardiovascular profiles. Blood samples from control and CKD rats were collected at 0, 3, 9 and 15 weeks in order to evaluate: renal function, hemorheological parameters, iron metabolism, blood lipids, peripheral sympathetic and serotonergic systems, redox state and inflammatory markers. BP, tissues uophism indexes and kidney histomorphology were also assessed. Our data is consistent with a sustained moderate degree of CKD with a quickly compensated modest anaemia, though presenting iron metabolism disturbances. Despite the reasonable degree of functionality of the remnant kidney, as suggested by the anaemia correction and by the kidney hypertrophy, several important cardiovascular modifications were developed. Our model presented hypertension, dyslipidaemia, erythropoietic disturbances, sympathetic activation and oxidative stress. This model might be a good tool to study the cellular/molecularmechanisms underlying moderate stages of CKD and to evaluate the therapeutics efficacy for prevention, treatment/correction of cardiorenal anaemia syndromes and complications in early stages.
- Cardiac antiapoptotic and proproliferative effect of recombinant human erythropoietin in a moderate stage of chronic renal failure in the ratPublication . Teixeira, M.; Rodrigues-Santos, P.; Garrido, P.; Costa, E.; Parada, B.; Sereno, J.; Alves, R.; Belo, L.; Teixeira, F.; Santos-Silva, A.; Reis, F.Objective: Recombinant human erythropoietin (rhEPO) therapy under circumstances of moderate chronic renal failure (CRF), with yet lower kidney and heart lesion, may have a protective cardiac effect beyond the correction of anemia, whose mechanism deserves better elucidation, namely by clarifying the impact on gene expression profile of markers of apoptosis, inflammation, proliferation, angiogenesis, and lesion/stress in the heart. Materials and Methods: Four groups of rats were studied over a period of 15 weeks (n=7 each): control-without surgery and without drug treatment; rhEPO-treated with 50 IU/kg/week of rhEPO-beta; CRF-submitted to partial nephrectomy (3/4); CRF + rhEPO-CRF with rhEPO treatment after the 3rd week of surgery. The heart was collected in order to evaluate the gene expression, by real-time qPCR, of markers of apoptotic machinery, inflammation/immunology, proliferation/ angiogenesis, and lesion/stress. Results: The main findings obtained were (a) CRF rats have demonstrated overexpression of EPO-R in the heart without changes on EPO expression, together with overexpression of Bax/Bcl2 ratio, PCNA, and IL-2; (b) rhEPO therapy on the heart of the rats with CRF induced by partial 3/4 nephrectomy promoted nonhematopoietic protection, demonstrated by the apoptosis prevention, viewed by the Bax/Bcl2 balance, by the promotion of proliferation, due to PCNA increment, and by the immunomodulatory action, expressed by a trend to prevent the IL-2 increment. Conclusion: In this model of moderate CRF, rhEPO treatment showed important cardiac nonhematopoietic effects, expressed mainly by the antiapoptotic and the proproliferative action, suggesting that early rhEPO therapy in moderate stages of CRF might have further therapeutic benefits.
- Effect of recombinant human erythropoietin in a rat model of moderate chronic renal failure – focus on inflammation, oxidative Stress and function/renoprotectionPublication . Garrido, P.; Reis, F.; Costa, E.; Almeida, A.; Parada, B.; Teixeira-Lemos, E.; Santos, P.; Alves, R.; Sereno, J.; Pinto, R.; Tavares, C.A.; Figueiredo, A.; Rocha-Pereira, P.; Belo, L.; Santos-Silva, A.; Teixeira, F.Background/Aims: Chronic renal failure (CRF) patients develop anaemia, thus promoting cardiovascular complications, which seems to be favoured by the low kidney erythropoietin (EPO) production. The renal insufficiency degree might determine the moment to start recombinant human EPO (rhEPO) therapy. It has been attributed important non-hematopoietic effects to rhEPO, which might underlie cardio and renoprotection. This work aimed to evaluate the effect of rhEPO in a rat model of moderate CRF, focusing on inflammation, oxidative stress and function/renoprotection. Methods: Four groups (n=7) of male Wistar rats were evaluated during a 15 week follow-up period: control (without treatment); rhEPO (50 IU/Kg/wk Recormon®); CRF and CRF+rhEPO. Blood samples were collected at the beginning and 3, 9 and 12 weeks after 3/4 nephrectomy, in order to evaluate: renal function, haematological parameters, iron metabolism and serum proliferative (TGF-B1), inflammatory (TNF-a, CRP, IL-2 and IL-1B) and redox status (MDA, TAS and 3-NT) markers. Kidney gene expression of Il2, Vegf, Nos2 and Nos3 were assessed by real-time PCR. Blood pressure, heart rate and tissues trophy indexes were also estimated. Results: Our data are consistent with a sustained moderate degree of CRF with development of moderate and corrected anaemia and hypertension. The remnant kidney showed a proliferative profile, with increased mass (hypertrophism), upregulated tissue Vegf gene expression, accompanied by increased levels of serum TGF-B1. Serum 3-NT was augmented, suggesting oxidative stress, which was accompanied by a trend to higher kidney Nos gene expression of both isoforms. rhEPO treatment was able to partially attenuate renal function markers, totally correct anaemia, also demonstrating a proliferative and antioxidant action, suggesting renoprotection. Conclusion: This study suggests that rhEPO therapy might be recommended in moderate CRF stages in order to efficiently correct not only the anaemia but also the underlying deleterious mechanisms, due to a proliferative and antioxidant action on the remnant kidney.
- Erythropoietin doping as cause of sudden death in athletes: an experimental studyPublication . Piloto, N.; Teixeira, H.M.; Teixeira-Lemos, E.; Parada, B.; Garrido, P.; Sereno, J.; F. Pinto, A.F.; Costa, Elísio; Belo, L.; Santos-Silva, A.; Pinto, R.; Couceiro, P.; Neto, P.; Xavier, F.; Carvalho, L.; Teixeira, F.; Reis, F.Aims: To evaluate the cardiovascular (CV) effects of rhEPO treatment in rats under chronic aerobic exercise and to assess the probable cause of sudden death in one rat. Protocol: Male Wistar rats: control - sedentary; rhEPO - 50 IU/Kg/3xwk; swimming (EX) -1 hr, 3x/wk; EX+EPO. Hematology, catecholamines and serotonin, redox status and inflammation, were assessed. One rat of EX+EPO group suffered a sudden death episode. Results: rhEPO treatment in trained rats promoted several markers of increased CV risk. The sudden death rat tissues presented: lungs without signs of drowning; brain with vascular congestion; LV hypertrpphy and deregulations of cardiac fibers, together with a "cardiac liver", suggesting the hypothesis of heart failure as cause of death. Conclusion: The sudden death of a EX+EPO rat, due to a cardiac episode, together with the increased CV risk profile, strongly suggest a high life risk associated to the continuous rhEPO doping. The anatomo-pathological studies were determinant to establish the cause of death.
- Hemorheological and cardiovascular effects of erythropoietin in a rat model of sports dopingPublication . Piloto, N.; Teixeira, HM; Garrido, P.; Teixeira-Lemos, E.; Teixeira, M.; Parada, B.; Sereno, J.; Pinto, R .; Alves, R.; Santos, P.; Romão, AM; Nunes, S.; Neto, P.; Carvalho, L.; Couceiro, P.; Xavier, F.; Rocha-Pereira, P.; Costa, Elísio; Belo, L.; Santos-Silva, A.; Teixeira, F.; Reis, F.Recombinant human erythropoietin (rhEPO) has been therapeutically used for correction of anaemia. However, due to the increase in circulating red blood cells (RBCs) it promotes, thus increasing oxygen delivery to muscles and improving performance in sport, it has been also illegally used as sports doping. Besides the well known increase of hematocrit and blood viscosity; which might cause serious complications for the athletes, other disturbances could occur, whose mechanisms remain to be fully elucidated. This study aimed to evaluate the hemorheological and cardiovascular effects of administration of rhEPO to rats under chronic aerobic exercise. A ten week-protocol was performed in four male Wistar rat groups: control — sedentary; rhEPO — 50 IV/kg, 3 times/wk; exercised (EX) — swimming for 1 hr, 3 times/ wk; EX+rhEPO. rhEPO in trained rats promoted erythrocyte count increase, hypertension, heart hypertro-phy, sympathetic and serotonergic overactivation, as well as a trend to increased oxidative stress. In conclusion, rhEPO doping in rats under chronic exercise promotes not only the expected increased hematocrit, but also other serious deleterious cardiovascular and thromboembolic modifications, including live risk, which might be known and assumed by all sports authorities, including athletes and their physicians.
- Hypertension induced by immunosuppressive drugs: a comparative analysis between sirolimus and cyclosporinePublication . Reis, F.; Parada, B.; Lemos, E. Teixeira de; Garrido, P.; Dias, A.; Piloto, N.; Baptista, S.; Sereno, J.; Eufrásio, P.; Costa, Elísio; Rocha-Pereira, P.; Santos-Silva, A.; Figueiredo, A.; Mota, A.; Teixeira, F.The purpose of this study was to compare the effects of sirolimus (SRL) vs cyclosporine (CsA) concerning the cardiovascular mechanisms hypothetically contributing to hypertension development. Three rat groups were studied: control (vehicle), CsA (5 mg/kg/d), and SRL (1 mg/kg/d). The following parameters were evaluated after 7 weeks of treatment: blood pressured (BP) and heart rate (HR; tail cuff), lipid profile, hematology, plasma and platelet 5-HT and catecholamines (HPLC-ECD), and oxidative equilibrium (serum malondialdehyde [MDA] and total antioxidant status [TAS]). Systolic (SBP) and diastolic blood pressure (DBP) values were higher (P < .001) in both the CsA (146.2 +/- 4.5 and 124.9 +/- 4.5 mm Hg) and SRL (148.9 +/- 4.8 and 126.4 +/- 6.0 mm Hg) groups vs the controls (115.9 +/- 3.3 and 99.1 +/- 2.0 mm Hg). However, HR values were elevated in CsA but not SRL animals. The dyslipidemic pattern of CsA was even more enhanced in the SRL group, with significantly higher low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) levels vs CsA (P<.05); red blood cells, hematocrit, hemoglobin concentration, mean platelet volume, and platelet distribution width were significantly (P<.05) higher in the SRL vs CsA group. The pro-oxidative profile (increased MDA/TAS) in the CsA group was not reproduced in the SRL cohort. While plasma and platelet 5-HT were elevated in SRL rats, catecholamine content was higher in CsA animals. In conclusion, this study demonstrated that CsA and SRL produce identical hypertensive effects. However, while CsA promotes oxidative stress and sympathetic activation, SRL mainly interferes with lipid profile and hematological parameters. Thus, the hypertensive effects of CsA, a calcineurin inhibitor, and of SRL, an mTOR inhibitor, are associated with impairment of distinct cardiovascular pathways.
- Recombinant human erythropoietin therapy has beneffical cardio-renal effects on moderate stages of chronic renal failure in the ratPublication . Garrido, P.; Reis, F.; Costa, Elísio; Parada, B.; Piloto, N.; Sereno, J.; Teixeira, A.; Pinto, R.; Figueiredo, A.; Alves, R.; Rocha-Pereira, P.; Belo, L.; Santos-Silva, A.; Teixeira, F.This study aimed to assess the cardio-renal effects of rhEPO therapy on an animal model of moderate chronic renal failure (CRF). Four groups (n =7) of male rat were evaluated during a 12-week follow up period: control; rhEPO: 50 IU/Kg/wk; CRF: two-stage 3/, nephrectomy; CRF+ rhEPO (start after the 3'd wk of surgery). Renal function, haematology and serum inflammation and redox status were assessed. rhEPO treatment was able to partially attenuate renal function markers, totally correct anaemia, also showing a proliferative and antioxidant action, due to increased serum TGF-13I and decreased 3-NT. In conclusion, rhEPO therapy might be recommended in moderate CRF stages in order to efficiently correct not only the underlying anaemia but also the deleterious cardio-renal effects, due to a proliferative and antioxidant renoprotective action.