Browsing by Author "Pires, M. J."
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- Effect of chronic therapy with chaethomellic acid A on renal fibrosis in 5/6 nephrectomized rats: A preliminary studyPublication . Nogueira, A.; Vala, Helena; Nóbrega, C.; Pires, C. A.; Colaço, B.; Oliveira, P. A.; Pires, M. J.Objective: The 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.
- New therapeutic approaches on chronic kidney diseasePublication . Nogueira, A.; Vala, Helena; Nóbrega, Carmen; Pires, C. A.; Colaço, B.; Oliveira, P. A.; Pires, M. J.Introduction: chronic kidney disease is a serious public health problem that affects millions of patients worldwide. So, the main research goals in the CKD patients are the research of new therapeutic approaches capable of slowing down the progression to end-stage renal disease. Objective: the aim of this work, was to evaluate the effects of chronic administration of chaetomellic acid A (CAA), which selectively blocks H-Ras farnesylation, on kidney chronic lesions in 5/6 nephrectomized Wistar rats, an animal model of chronic renal disease. Material and methods: sixty male Wistar rats (Rattus norvergicus) were housed under controlled conditions. After seven weeks of acclimatization, rats (weighing 359 to 402 g) were sham-operated (SO) or submitted to 5/6 nephrectomy (RMR). One week after surgery surviving animals (n=53) 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 intraperitoneally administered (0.23 µg/Kg) three times a week for six months. Six months after the surgical procedure, in the left kidney of each animal was evaluated the mean cortical and medullary echogenicity by two-dimensional ultrasonography. Then, the kidneys were removed, fixed in 10% neutral-buffered formalin and processed for routine histopathological diagnosis and chronic lesions were evaluated, by Hematoxylin-Eosin, reticulin and Masson trichrome methods, for severity. 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 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.Conclusion: this data suggests that pharmacological inhibition of H-Ras proteins activation may be a future strategy in the prevention of end-stage renal disease.