Protective Effect of Paricalcitol on Cyclosporine-Induced Renal Injury in Rats

Abstract

We evaluated the protective effect of paricalcitol on cyclosporine (CsA)–induced renal injury using an experimental model of chronic CsA nephropathy. Paricalcitol (50 and 200 ng/kg/d) was concomitantly administered with CsA (15 mg/kg/d) for 28 days in rats. We assessed the effects of paricalcitol by measuring degree of the tubulointerstitial fibrosis (TIF) and inflammation, a profibrotic cytokine (βig-h3), a proapoptotic gene (caspase-3), apoptotic cell death, and oxidative stress. The CsA-treated rats showed increased TIF and inflammatory cell infiltration, but paricalcitol treatment (200 ng/kg) significantly decreased those compared with the CsA-alone group. The expression of βig-h3, a biologic marker of transforming growth factor β1, which was increased in the CsA group, also decreased with paricalcitol treatment. The increased rates of excretion of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and expression of tissue 8-OHdG produced by CsA treatment were significantly attenuated by paricalcitol treatment. The increased expression of caspase-3 and number of TUNEL-positive cells in the CsA group were decreased with concomitant paricalcitol treatment. The effect of paricalcitol was more evident high among the rather than low-dose cohort. In conclusion, paricalcitol showed antiinflammatory and antifibrotic effects. This finding may provide a rationale for use of paricalcitol in CsA-induced renal injury.