Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats

Ann R Coll Surg Engl. 2013 Oct;95(7):489-94. doi: 10.1308/003588413X13629960049117.

Abstract

Introduction: Despite the developments in modern medicine, acute renal injury is still a challenging and common health problem. It is well known that ischaemia and reperfusion takes place in pathological mechanisms. Efforts to clarify the pathophysiology and interventions to improve outcomes are essential. Our study aimed to investigate whether the prophylactic use of paricalcitol is beneficial in renal ischaemia/reperfusion (I/R) injury.

Methods: Twenty-four Wistar albino rats were assigned randomly to four groups. Right nephrectomies were performed at the time of renal arterial clamping. Sham surgery was performed on the rats in group 1. For the rats in group 2, the left renal artery was clamped for 45 minutes. The rats in group 3 received paricalcitol for seven days (0.2μg/kg/day); following this, a right nephrectomy and left renal arterial clamping were not performed. The rats in group 4 received paricalcitol for seven days (0.2μg/kg/day); following this, a right nephrectomy and left renal arterial clamping for 45 minutes were performed. Tissue thiobarbituric acid reactive substances (TBARS), superoxide dismutase, sulfhydryl groups as well as nitric oxide metabolites, serum urea and creatinine levels were measured for all four groups.

Results: In group 4, there were some improvements in terms of TBARS, nitrite, nitrate, superoxide dismutase and creatinine levels. In the histopathological evaluation, paricalcitol therapy improved tubular necrosis and medullar congestion but there was no significant difference in terms of tubular cell swelling, cellular vacuolisation or general damage. Immunohistopathological examination revealed lower scores for vascular endothelial growth factor in the group 4 rats than in group 2.

Conclusions: Paricalcitol therapy improved renal I/R injury in terms of serum and histopathological parameters. These potential beneficial effects need to be further investigated.

MeSH terms

  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / surgery
  • Animals
  • Constriction
  • Ergocalciferols / pharmacology*
  • Immunohistochemistry
  • Kidney / blood supply
  • Nephrectomy
  • Nitric Oxide / metabolism
  • Oxidoreductases / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Receptors, Calcitriol / drug effects*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Ergocalciferols
  • Receptors, Calcitriol
  • Thiobarbituric Acid Reactive Substances
  • Nitric Oxide
  • paricalcitol
  • Oxidoreductases