Nogueira, António José M.Vala, HelenaNóbrega, CarmenPires, Carlos AndréColaço, Bruno JorgeOliveira, Paula A.Pires, Maria João2019-11-112019-11-112018Nogueira, António José M.; Vala, Helena; Nóbrega, Carmen; Pires, Carlos André; Colaço, Bruno; Oliveira, Paula; Pires, Maria João (2018). New therapeutic approaches to chronic kidney disease. Journal of Comparative Pathology. ISSN 1532-3129. 158, special number, p. 1271532-3129http://hdl.handle.net/10198/19798The 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.engChaetomellic acid AIntroduction: T5/6 nephrectomized ratsconference object10.1016/j.jcpa.2017.10.098