Effect of chronic therapy with chaethomellic acid A on renal fibrosis in 5/6 nephrectomized rats: A preliminary study

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