Abstract: TH-PO249

Paricalcitol Ameliorates Radiocontrast-Induced Nephropathy by Regulating Mitophagy

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Park, Dong Jun, Changwon Gyeongsang National University Hospital and Gyeongsang National University, Changwon-si, Korea (the Republic of)
  • Lee, Tae won, Changwon Gyeongsang National University Hospital and Gyeongsang National University, Changwon-si, Korea (the Republic of)
  • Bae, Eunjin, Changwon Gyeongsang National University Hospital and Gyeongsang National University, Changwon-si, Korea (the Republic of)
  • Cho, Hyun Seop, Gyeongsang National University Hospital and Gyeongsang National University, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
  • Jang, Ha nee, Gyeongsang National Univ. Hospital, Jinju-si, Korea (the Republic of)
  • Park, Hee jung, Gyeongsang national university hospital, Jinju, Jinju-si, Korea (the Republic of)
  • Chang, Se-Ho, Gyeongsang National University Hospital and Gyeongsang National University, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
Background

Radiocontrast-induced nephropathy (RCIN) is an important problem in clinical settings. However, strategies to prevent RCIN have been suboptimal. Paricalcitol was recently found to be effective in a variety of renal animal models, so it was hypothesized that paricalcitol would prevent RCIN

Methods

RCIN was induced in rats by injection of the radiocontrast medium Ioversol in addition to inhibition of prostaglandin and nitric oxide synthesis. Rats were randomly assigned to four groups: healthy controls (Con, n=10), received paricalcitol only (Parical, n=10), ioversol (CONT, n=10), and received paricalcitol before ioversol injection (Parical+CONT, n=10). Rats were treated with either paricalcitol (0.3 mg/kg, i.p) or saline (equal volume, i.p.) at 24 h and 30 minutes prior to ioversol injection.

Results

Administration of two doses of paricalcitol before the induction of nephropathy significantly reduced the renal dysfunction and histologic tubular injury. The apoptosis of renal tubular cells was inhibited by paricalcitol. Oxidative stress markers such as 8-OhdG and NOX-2, NADPH oxidase, were highly expressed in nephropathy rat model, but attenuated by paricalcitol administration. β-galactosidase, one of markers of cellular senescence, increased in tubules after contrast infusion. This was alleviated by paricalcitol. Furthermore, the expression of LC3, PINK1, and Parkin, representatives of mitochondrial autophagy, after radiocontrast injection was highly attenuated by administration of paricalcitol, suggesting that the effects of paricalcitol might be mediated by the autophagy pathway.

Conclusion

These findings suggest that paricalcitol may have potential as a new therapeutic approach to prevent RCIN.