The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction

Abstract

Purpose. This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.

Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and arteriolosclerosis in a rat model of chronic kidney disease

“…According to Qian et al [33], CAA has a reduced off-target toxicity relative to others farnesyltransferase inhibitors. In fact, as we have previously discussed [25], we did not observe adverse effects after the administration of CAA to rats. However, possibly chronic administration of CAA (0.23 µg/Kg three times a week) may have some toxicity in rats with CKD, while in healthy animals, administration of CAA is innocuous.…”

“…Furthermore, CAA administration in rats, after brain damage induced by an excitotoxic stimulus, significantly reduced superoxide production [19]. Also, an in our previous study [25], we have observed that CAA attenuate 5/6 RMR-induced oxidative stress in rats. Oxidative stress plays an important role in renal injury induced by 5/6 RMR [62,63].…”

“…Therefore, we have evaluated the effect of CAA, which selectively blocks Ha-Ras farnesylation [19], on renal fibrosis. To date, relatively few studies have assessed the effects of the CAA in experimental models of kidney diseases [7,20,21,25].…”

“…Blood and urine samples were collected at the sixth month as we have previously described [25]. Plaα creatinine, urinary creatinine and proteinuria were measured using a chemistry analyser (Daytona® Rx, Randox) as per manufacturers' instructions.…”

“…Systolic blood pressure (SBP) was measured through femoral artery catheterization as we have previously described [25]. After that, the rats were sacrificed using an overdose of anesthesia followed by exsanguination by cardiac puncture as indicated by the Federation of European Laboratory Animal Science Associations [26].…”