1. Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and arteriolosclerosis in a rat model of chronic kidney disease.
- Author
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Nogueira A, Vala H, Vasconcelos-Nóbrega C, Faustino-Rocha AI, Pires CA, Colaço A, Oliveira PA, and Pires MJ
- Subjects
- Animals, Arteriolosclerosis drug therapy, Arteriolosclerosis metabolism, Drug Administration Schedule, Genes, ras drug effects, Genes, ras physiology, Glomerulosclerosis, Focal Segmental drug therapy, Glomerulosclerosis, Focal Segmental metabolism, Male, Protein Prenylation drug effects, Protein Prenylation physiology, Rats, Rats, Wistar, Renal Agents pharmacology, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic metabolism, Time Factors, Treatment Outcome, Arteriolosclerosis diagnostic imaging, Disease Models, Animal, Glomerulosclerosis, Focal Segmental diagnostic imaging, Renal Agents therapeutic use, Renal Insufficiency, Chronic diagnostic imaging
- Abstract
The 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 0.23μg/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., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
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