Percorrer por autor "Teixeira, Frederico"
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- Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat – focus on serum, urine, gene and protein renal expression biomarkersPublication . Sereno, José; Nunes, Sara; Rodrigues-Santos, Paulo; Vala, Helena; Rocha-Pereira, Petronila; Fernandes, João; Santos-Silva, Alice; Teixeira, Frederico; Reis, FlávioProtocols of conversion from cyclosporine A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (𝑛 = 6) were teste during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF- β , NF-𝜅β , mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF- β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL
- Effects of Sitagliptin Treatment on Dysmetabolism, Inflammation, and Oxidative Stress in an Animal Model of Type 2 Diabetes (ZDF Rat)Publication . Ferreira, Liliana; Teixeira-de-Lemos, Edite; Pinto, Filipa; Parada, Belmiro; Mega, Cristina; Vala, Helena; Pinto, Rui; Garrido, Patrícia; Sereno, José; Fernandes, Rosa; Santos, Paulo; Velada, Isabel; Melo, Andreia; Nunes, Sara; Teixeira, Frederico; Reis, FlávioThe purpose of this paper is to evaluate the chronic effect of sitagliptin on metabolic profile, inflammation, and redox status in the Zucker Diabetic Fatty (ZDF) rat, an animal model of obese type 2 diabetes. Diabetic and obese ZDF (fa/fa) rats and their controls (ZDF +/+) were treated during 6 weeks with vehicle (control) and sitagliptin (10 mg/kg/bw). Glucose, HbA1c, insulin, Total-c, TGs, IL-1beta, TNF-alpha, CRPhs, and adiponectin were assessed in serum and MDA and TAS in serum, pancreas, and heart. Pancreatic histology was also evaluated. Sitagliptin in diabetic rats promoted a decrease in glucose, HbA1c, Total-c, and TGs accompanied by a partial prevention of insulinopenia, together, with a decrease in CRPhs and IL-1beta. Sitagliptin also showed a positive impact on lipid peroxidation and hypertension prevention. In conclusion, chronic sitagliptin treatment corrected the glycaemic dysmetabolism, hypertriglyceridaemia, inflammation, and hypertension, reduced the severity of the histopathological lesions of pancreatic endocrine and exocrine tissues, together with a favourable redox status, which might be a further advantage in the management of diabetes and its proatherogenic comorbidities.
- 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.
- Sirolimus ameliorates cyclosporin-induced nephrotoxicity in a rat model – focus on renal lesions, oxidative stress, inflammation, proliferation and angiogenesisPublication . Sereno, José; Romão, Ana M.; Teixeira, Margarida; Parada, Belmiro; Santos, Paulo R.; Alves, Rui; Mega, Cristina; Vala, Helena; Lemos, Edite T.; Teixeira, Frederico; Reis, FlávioSirolimus (SRL) have been pointed as a feasible option for minimize the use of cyclosporine A (CsA), especially because os putatively less nephrotoxicity. However, the cellular mechanism underlying the renoprotection remains to be elucidated, and the clinical data is yet insufficient. This stuty aimed to characterize the histological lesions and the molecular pathways implicated in CsA-induced nephropathy and prevention when converted to SRL.
- Transition from Cyclosporine-Induced Renal Dysfunction to Nephrotoxicity in an in Vivo Rat ModelPublication . Sereno, José; Rodrigues-Santos, Paulo; Vala, Helena; Rocha-Pereira, Petronila; Alves, Rui; Fernandes, João; Santos-Silva, Alice; Carvalho, Eugénia; Teixeira, Frederico; Reis, FlávioCyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and would help clinical decisions. This study aimed to clarify these issues, using a rat model of short- and long-term CsA (5 mg/kg bw/day) treatments (3 and 9 weeks, respectively). Renal function was assessed on serum and urine; kidney tissue was used for histopathological characterization and gene and/or protein expression of markers of proliferation, fibrosis and inflammation. In the short-term, creatinine and blood urea nitrogen (BUN) levels increased and clearances decreased, accompanied by glomerular filtration rate (GFR) reduction, but without kidney lesions; at that stage, CsA exposure induced proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF-β1), factor nuclear kappa B (NF-κβ) and Tumor Protein P53 (TP53) kidney mRNA up-regulation. In the long-term treatment, renal dysfunction data was accompanied by glomerular and tubulointerstitial lesions, with remarkable kidney mRNA up-regulation of the mammalian target of rapamycin (mTOR) and the antigen identified by monoclonal antibody Ki-67 (Mki67), accompanied by mTOR protein overexpression. Transition from CsA-induced renal dysfunction to nephrotoxicity is accompanied by modification of molecular mechanisms and biomarkers, being mTOR one of the key players for kidney lesion evolution, thus suggesting, by mean of molecular evidences, that early CsA replacement by mTOR inhibitors is indeed the better therapeutic choice to prevent chronic allograft nephropathy.