Percorrer por autor "Pires, Carlos André"
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- Ação do ácido quetomélico nas alterações hematológicas induzidas pela redução de 5/6 de massa renal em ratosPublication . Fonte, Elizabete; Nogueira, António José M.; Pires, Carlos André; Colaço, Bruno Jorge; Oliveira, Paula A.; Pires, Maria JoãoA doença renal crónica está associada com o desenvolvimento de anemia devido principalmente à diminuição da produção de eritropoetina. O ácido quetomélico (AC) é um potente inibidor seletivo da farnesil transferase e, desta forma, inibe as vias de sinalização que levam à progressão da fibrose renal. Assim, o objectivo deste trabalho foi o de estudar os efeitos do tratamento crónico com o AC nas alterações hematológicas induzidas pela redução de 5/6 de massa renal (RMR). Neste estudo foram utilizados 70 ratos machos da estirpe Wistar. Uma semana após a redução cirúrgica de 5/6 de massa renal, os animais foram divididos em quatro grupos experimentais: CO: animais em que se simulou a cirurgia e sem tratamento; CO+AC: animais em que se simulou a cirurgia e tratados com o AC; RMR: animais com RMR e não tratados; RMR+AC: animais com RMR e tratados com o AC. O tratamento foi administrado por via intraperitoneal, durante seis meses. Para o estudo hematológico procedeu-se à contagem manual, em câmara de Neubauer, do número total de eritrócitos e de leucócitos, à determinação do microhematócrio, à contagem diferencial de leucócitos e à estimativa do número total de plaquetas no esfregaço de sangue corado com Diff-Quick. Nos grupos RMR e RMR+AC observou-se um aumento estatisticamente significativo (p<0.01) do número total de eritrócitos, do microhematócrito, do número total de leucócitos e das plaquetas, em relação aos grupos CO e CO+AC. Deste modo, os resultados deste estudo sugerem que em ratos Wistar com doença renal crónica, o tratamento com o AC, durante seis meses, não diminui a gravidade da anemia, da leucocitose e da trombocitose induzidas pela redução de 5/6 de massa renal.
- Effect of chronic therapy with chaethomellic acid A on renal fibrosis in 5/6 nephrectomized rats: a preliminary studyPublication . Nogueira, António José M.; Vala, Helena; Nóbrega, Carmen; Pires, Carlos André; Colaço, Bruno Jorge; Oliveira, Paula A.; Pires, Maria JoãoThe high prevalence of chronic kidney disease underscores the failure to provide therapies to effectively halt, prevent, and/or reverse renal fibrosis. Thus, the aim of this study was to evaluate the effect of chronic treatment with chaethomellic acid A (CA) on renal fibrosis associated to 5/6 nephrectomy. Methods: Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats were placed in four experimental groups: RMR: rats without treatment (n=13); RMR+CA: rats treated with CA (n=13); SO: rats without treatment (n=13); SO+CA: rats treated with CA (n=13). CA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Renal samples were scored for the following lesions: glomerulosclerosis, interstitial fibrosis, arteriolosclerosis and interstitial inflammation. Results: Animals from the SO and SO+CA groups presented no kidney histological changes. Glomerulosclerosis, interstitial fibrosis and arteriolosclerosis scores were significantly lower (p< 0.001) in RMR+CA group when compared with RMR group. There were no significantly differences in interstitial inflammation score between RMR+CA and RMR groups. Conclusions: This preliminary data suggests that pharmacological inhibition of Ras (small GTPase proteins) activation may be a future strategy in the prevention of renal fibrosis.
- The effects of long-term chaetomellic acid a administration on renal function and oxidative stress in a rat model of renal mass reductionPublication . Nogueira, António José M.; Peixoto, Francisco P.; Oliveira, Maria Manuel; Pires, Carlos André; Colaço, Bruno Jorge; Oliveira, Paula A.; Pires, Maria JoãoThis study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in amodel of renalmass reduction. Methods.MaleWistar ratswere subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 μg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAAadministration significantly increased catalase andGR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio.No significant differences were found between theRMRgroups in any of the parameters of renal function.However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.
- Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and arteriolosclerosis in a rat model of chronic kidney diseasePublication . Nogueira, António José M.; Vala, Helena; Vasconcelos-Nóbrega, Cármen; Rocha, Ana Isabel Faustino; Pires, Carlos André; Colaço, Aura; Oliveira, Paula A.; Pires, Maria JoãoThe high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO:SO rats without treatment (n = 13); SO + CAA: SO rats treated with CAA (n = 13); RMR:RMR rats without treatment (n = 14); and RMR + CAA:RMR rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 μg/kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p < 0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p < 0.001) in the RMR + CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR + CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease.
- New therapeutic approaches to chronic kidney diseasePublication . Nogueira, António José M.; Vala, Helena; Nóbrega, Carmen; Pires, Carlos André; Colaço, Bruno Jorge; Oliveira, Paula A.; Pires, Maria JoãoThe main research goal in patients with chronic kidney disease (CKD) is the development of new therapeutic approaches capable of slowing down the progression to end-stage renal disease. The aim of this work was to evaluate the effects of long-term administration of chaetomellic acid A (CAA), which selectively blocks H-Ras farnesylation, on chronic kidney lesions in 5/6 nephrectomized Wistar rats, an animal model of chronic renal disease. Materials and Methods: Sixty male Wistar rats were sham-operated (SO) or submitted to 5/6 nephrectomy (RMR). One week after surgery, surviving animals were distributed into four groups: SO–SO rats receiving no treatment (n = 13); SO+CAA–SO rats receiving CAA treatment (n = 13); RMR–RMR rats receiving no treatment (n = 14); RMR+CAA–RMR rats receiving CAA treatment (n = 13). CAA was administered intraperitoneally three times a week for 6 months. Renal fibrosis was evaluated by ultrasonography and histopathological analysis. All experimental procedures followed the European (European Directive 2010/63/EU) and National (Decree-Law 113/2013) legislation on the protection of the animals used for scientific purposes. Results: The kidneys of the RMR animals treated with CAA showed a significant decrease in medullary echogenicity (P <0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (P <0.001) in the RMR+CAA group when compared with the RMR group. Conclusion: These data suggest that pharmacological inhibition of H-Ras proteins activation may be a future strategy in the prevention of end-stage renal disease.