A Rat Model for Cyclosporine A Nephrotoxicity: A Study on Wistar Strain Rats

Nephrotoxicity is a side effect of cyclosporine A (CsA), which is used after transplantation. In CsA-treated patients, factors other than the drug may also have renal and cardiovascular effects. Therefore, experimental models are needed to study adverse effects of only CsA. Since the study was planned to suggest an ideal model for CsA nephrotoxicity, the most appropriate route, duration and dose of administration were determined in male Wistar rats treated with CsA for making functional and morphological nephrotoxicity. CsA were intraperitoneally or subcutaneously administrated to the four groups of rats, in each 2-3, at doses of 20, 30, 40 and 50 mg/kg bw/day, respectively. According to data of this pre-study, study groups were subcutaneously treated with CsA at a dose of 30 mg/kg/day for 30 days, and saline was used for control group. On zero, 10th, 20th and 30th days of the study, plasma BUN and creatinine (Cr) and urine urea nitrogen, Cr and microprotein were analyzed. Urine volumes and weights were recorded. Clearance (CCr) was calculated. Renal tissues were also assessed histologically. There was an increase in plasma BUN and decreases in daily Cr output, CCr, body weights and urine volumes in CsA group by the 10th day of the study. Plasma Cr and urine nitrogen levels were higher on the 30th day, in addition to these toxic effects. In proximal tubules mostly vacuolization, dilatation, necrosis and atrophy were observed in renal histopathology. Our results show that, at a dose of 30 mg/kg/day CsA administrated to male Wistar rats for 30 days resulted in functional and morphologic nephrotoxicity, and also this experimental model may be used in the studies of CsA nephrotoxicity, successfully.