title: 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.
authors.affiliation: Convergent Research Consortium for Immunologic Disease, Seoul St Mary's Hospital, Catholic University of Korea, Seoul, Korea.
authors.forename: S G
authors.initials: SG
authors.lastname: Piao
authors.forename: J C
authors.initials: JC
authors.lastname: Song
authors.forename: S W
authors.initials: SW
authors.lastname: Lim
authors.forename: B H
authors.initials: BH
authors.lastname: Chung
authors.forename: B S
authors.initials: BS
authors.lastname: Choi
authors.forename: C W
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects* / Q000293:injuries; D008264:Macrophages / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D016572:Cyclosporine; D003849:Deoxyguanosine; D004872:Ergocalciferols; D016326:Extracellular Matrix Proteins; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C084656:paricalcitol