ESAV - DZERV - Resumos de eventos científicos não indexados à WoS/Scopus
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Browsing ESAV - DZERV - Resumos de eventos científicos não indexados à WoS/Scopus by Subject "Chaetomellic acid A (CAA)"
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- 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.