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Kidney Week

Abstract: FR-PO072

Paricalcitol Ameliorates Cisplatin-Induced AKI by Inhibiting Cell Pyroptosis

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Zhang, Hao, The Third Xiangya Hospital of Central South University, Changsha, HUNAN, China
  • Jiang, Siqing, The third Xiangya Hospital, Central South University, CHANGSHA, China
  • Yi, Bin, The Third Xiangya Hospital of Central South University, Changsha, HUNAN, China
  • Hu, Zhaoxin, Central South University, CHANGSHA, China
Background

Cisplatin is a classic and effective chemotherapeutic agent, but its kidney toxicity has restricted its application. Vitamin D receptor (VDR), as an important nuclear receptor, is involved in the pathogenesis of acute and chronic kidney diseases. The VDR agonist paricalcitol exerts a protective effect on a variety of acute kidney injury. In this study, we investigated the protective effect and mechanism of paricalcitol in cisplatin-induced acute injury.

Methods

Eight week old male VDR KO mice and WT mice were randomly divided into 6 groups (n=6): (A) WT+Control, (B) WT+Cisplatin, (C) WT+Cisplatin+Paricalcitol, (D) KO, (E) KO+Cisplatin, (F) KO+Cisplatin+Paricalcitol. Pretreatment of paricalcitol (0.2mg/kg, intraperitoneally injected) was performed for five consecutive days. On the sixth day, cisplatin (20 mg/kg) was intraperitoneally injected to induce acute kidney injury (AKI). Samples were collected 72 hours after cisplatin injection. Real-time PCR and Western blot were used to detect the expressions of renal apoplexy-associated proteins such as NLRP-3, caspase-1 and IL-1β. Renal pathological specimens were subject to HE staining to assess the degree of renal tubular injury.

Results

1. 72 hours after cisplatin injection, mice in groups B, C, E and F became depressed and ate less. The levels of Cr, BUN and CysC were significantly higher in groups B, C, E and F (p<0.05), as compared with those in groups A and D, while mice in group E showed the most serious renal damage (p<0.05).
2. The mRNA and protein levels of NLRP-3, caspase-1 and IL-1β in groups B, C, E and F were significantly higher than those in group A and D (p<0.05). The increase of the three mRNAs/proteins in group E was most significant (p<0.05), and the expression of the three proteins in group C was lower than that in group B.
3. HE staining indicated that the renal tubular injury index in group C was significantly lower than that in group B (p<0.05). The renal tubular injury index was highest in group E (p<0.05).

Conclusion

VDR plays an important role in cisplatin-induced AKI. The VDR agonist paricalcitol possibly reduce cisplatin-induced AKI by inhibiting cell pyroptosis.

Funding

  • Government Support - Non-U.S.